# Appendix — Industrial Union Dept., AFL-CIO v. American Petroleum Institute > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40385006_0035%3A05 ## Record - **Collection:** Supreme Court brief - **Document type:** Appendix - **Published:** January 1, 1980 - **Citation:** 448 U.S. 607 ## Text ~ Supreme Court US | FILE a APPENDIX | MAY 18 1979 MICHAL RODAK, JR., CLERK Iu the Supreme Court of the United States OCTOBER TERM, 1979 Nos. 78-911 and 78-1036 INDUSTRIAL UNION DEPARTMENT, AFL-CIO, Petitioner =f) AMERICAN PETROLEUM INSTITUTE, ET AL. RAY MARSHALL, SECRETARY OF LABOR, Petitioner | AMERICAN PETROLEUM INSTITUTE, ET AL. ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT PETITIONS FOR A WRIT OF CERTIORARI FILED DECEMBER 7, 1978 (NO. 78-911) AND DECEMBER 26, 1978 (NO. 78-1036) CERTIORARI GRANTED FEBRUARY 21, 1979 Oe “Se aaa Ywisntmae? Iu the Supreme Court of the United States OCTOBER TERM, 1979 Nos. 78-911 and 78-1036 INDUSTRIAL UNION DEPARTMENT, AFL-CIO, Petitioner —V_ — AMERICAN PETROLEUM INSTITUTE, ET AL. RAY MARSHALL, SECRETARY OF LABOR, Petitioner — AMERICAN PETROLEUM INSTITUTE, ET AL. ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT TABLE OF CONTENTS OF APPENDIX Proceedings in the Court of Appeals and the Supreme Court * Page ETF aa ae) eRe IRN Cm er OTL mE Ne 1 Petition for Review Filed By The American Petroleum Insti- tute In the Court of Appeals, No. 78-1253 (selected as a representative example of the petitions filed) 000000000000... 12 Carcinogen Assessment Group, Preliminary Report on Popu- lation Risk to Ambient Benzene Exposures (appended to agency brief in court of appeals, June 8, 1978, as Adden- yh ASTER BPE ERT OS ao (Es Melick Vee ene EBS NPE Bea 15 * The opinion of the court of appeals appears in the separate appendix to the petition in No. 78-911. Copies of the briefs on the merits filed in the court of appeals have been lodged with the Clerk. ii TABLE OF CONTENTS OF APPENDIX Page Affidavit of Dr. Steven H. Lamm (appended to API’s reply brief in the court of appeals, June 19, 1978, as Appendix RRS ee A LL RTD EP A AE RO TR LNG ee AIR rd ome 30 Judgment of Court of panne 1 EES SARIE YL 2 Ret TRE SED Ro SP OT 37 ry: aE rs ss sepeagustibionsedecnenennes 38 Proceedings Before the Agency * Excerpted Testimony of Drs. Douglas Smith and Laigo of NIOSH, July 25, 1977 (Tr. 859-860) ..0....0..... ec eeeeeeeeeeeee 40 Excerpted Testimony of Dr, Richard Zeckhauser, July 29, 1977 (Tr. 2104-2112, 2141-2144, 2149-2154, 2156-2160, 2167-2169, 2180-2182, 2188-2190) 2... eee 40 Testimony of Dr. Howard Maibach, August 3, 1977 (Tr. SCSI T CR A we Bee earner do Sead en Sy Gee ee EON UO 58 Excerpted Testimony of Dr. Richard Wilson, August 4, 1977 (Tr. 2701-2711, 2721-2723, 2732-2742, 2753-2755, 2772- EERE IE RN R Oe EN E SE ETCEIN CR ON ORE 97 G. L. Conca and A. Maltagliati, “Study of the Percutaneous Benzene Absorption,” Med Lavoro 46:194-198, 1955 (list of references omitted) (OSHA translation) (Exh. 2-46) **.. 95 A. N. Cesaro, “Is Percutaneous Benzene Absorption Possi- ble?”, Med Lavoro 37:151-156, 1946 (list of references omitted) (OSHA translation) (Exh. 2-47) 2000000000... 101 J. Hanke, T. Dutkiewixz, and J. Piotrowski, “Absorption of Benzene Through the Sxin in Man,” Med Pracy 12:413-426, 1961 (list of references omitted) (OSHA translation) cos 5 Aaa a neee ds UPd orien Ue OY a reat NL FEES A ON a 107 Comments of the Council on Wage and Price Stability on the Proposed Benzene Standard (Exh. 41-28) 00000000000... 121 Written Statement of Dr. Richard Zeckhauser (Exh. RR RRIND, TALLER RENE AS has SERVER | Du SVR UREN AP AA PST CI aE 134 * The benzene standard and the Secretary’s statement of reasons for adopting the standard, 43 Fed. Reg. 5918 (1978), appear in the separate appendix to the petition in No. 78-911 at 34a-25la. The materials printed in this appendix do not constitute the entire administrative record compiled during the proceedings on the ben- zene standard, now on file in the Clerk’s office. To facilitate its use, the parties have lodged a typewritten index to the administrative record with the Clerk. ** Diagrams and graphs in this and other studies were omitted in printing but are available in the administrative record on file with the Clerk. ——— TABLE OF CONTENTS OF APPENDIX Written Statement of Dr. Howard I. Maibach, July 11, 1977 (omieiite omitted) CHEER. BRO) oon... cnc cscicciccescccessesscesseceise Written Statement of Dr. Richard Wilson (Exh. 149.B) DG ALI Lee Tr CA cd, A LD (The following materials are from the administrative record for the amendment to the benzene standard ) Excerpted Cross-examination of Grover Wrenn, snd 23, ge _ sR RENER LO ELCRN SUC FD AAaee Oe Excerpted Testimony of Dr. Roger W. Strassburg (The B. F. Goodrich Company), May 23, 1978 (Amend. Tr. 126-137, iar ES Rtg MEAL ANE Lg inks SS 8 EL ASR SO Re ar Excerpted Testimony of Mr. Roy N. Johnson (The General Tire & Rubber Company), May 23, 1978 (Amend. Tr. RE Ett iea TOaY TAPE UL Ss Me CALPE A WOR WANTS Lice: Oke USE RA ; Rubber Manufacturers Association (“RMA”) Motion for Stay, March 10, 1978, with attached OSHA statement (omiates) CAmsené. Bum. SE-F-8) .......-2-.-....02..............-....... Affidavit of James R. Sankey (The Goodyear Tire & Rubber Company), March 8, 1978 (Amend. Exh. 32-F-2) 00000000... Affidavit of Roger W. Strassburg (The B.F. Goodrich Com- pany), March 9, 1978 (Amend. Exh. 32-F-2) Affidavit of Robert E. Rehm (The General Tire & Rubber Company), March 9, 1978 (Amend. Exh. 32-F-2) Affidavit of Roy N. Johnson (The General Tire & Rubber Company), March 9, 1978 (Amend. Exh. 32-F-2) 0... Supplementary Affidavit of James R. Sankey (The Goodyear Tire & Rubber ere March 28, 1979 (Amend. Exh. EARNER ea ince Ay A APP OO Ob Se ERO Jane aT Affidavit of Robert W. Laundrie (The General Tire & Rubber Company), March 29, 1978 (Amend. Exh. 32-F-3) Secretary of Labor’s Supplemental Opposition To Petitioners Request For Stay Pending Judicial Review, April 12, 1978, cover page and page 67 (Amend. Exh. 32-A-3) . Affidavit of N.A. Daigle (The Firestone Tire & Rubber Company), April 13, 1978 (Amend. Exh. 32-F-4) Second Supplemental Affidavit of Roger W. Strassburg (The B. F. Goodrich Company), April 13, 1978) (exhibits omitted) (Amend. Exh. 32-F-4) 0... Amendment to Benzene Standard and Accompanying State- ment of Reasons, 43 Fed. Reg. 27962 (June 27, 1978) _... 180 187 197 202 205 209 216 222 224 227 230 232 234 1 . RELEVANT DOCKET ENTRIES [Title of court omitted in printing] AMERICAN PETROLEUM INSTITUTE ET AL. v. OSHA ET AL., NO. 78-1253 Feb. 2, 1978 Petition for review March 18, 1978 Order granting motion of Manufacturing Chemists Association, The American Iron And Steel Institute, and Chemical Specialties Manufacturers for leave to intervene. (LRM) (Also filed in 78-1257). March 21, 1978 Order granting motion of the Industrial Union Department, AFL-CIO to intervene (Also filed in 78-1257). April 18, 1978 Order continuing temporary stay entered on 3/13/78 pending disposition of petitions for review. Fur- ther granting motion of Independent Petroleum Associa- tion of America for leave to intervene. Further peti- tioners’ motion to consolidate is granted.[*] Further the motion to dismiss petition of review filed by Am. Petro- leum in No. 77-1973, API, et al v. OSHRC is carried with the case. Further the motion to correct captions in 78- 1253 and 78-1257 is granted. June 22, 1978 Case argued. June 23, 1978 Respondents’ letter dtd 6/22/78 with copy of amendments to the benzene standard issued June 27, 1978. (CE) (Also filed in consolidated cases). June 30, 1978 Petitioners’ letter dtd 6/30/78 with “pro- ducer” petitioners’ supplemental memorandum which addresses amendment to benzene standard and copy of Federal Register notice announcing amendment. (CE) (Also filed in consolidated cases). [*] This order consolidated cases nos. 78-1253, 1257, 1486, 1676, 1677, 1707, 1745, and any other cases seeking review of the benzene standard later transferred to the Fifth Circuit. 2 July 7, 1978 Order granting motion of petitioners, the Rub- ber Manufacturers Association, Inc., et al and the Arm- strong Rubber Company, et al. to filed amended petitions for review. (JPC-CC-GBT). July 11,1978 Filing Secretary of Labor’s motion to adjourn present supplemental briefing schedule and to set new briefing schedule on the merits of the amendment to the benzene standard. July 12,1978 Filing Response of Rubber Companies and Du Pont in opposition to motion to adjourn briefing schedule, etc. July 14,1978 Order denying the Secretary of Labor’s motion to adjourn present supplemental briefing schedule. Court does not desire briefs designed to enable it to reach the merits of the new standards. (CC) (Also filed in con- solidated cases). August 4, 1978 Filing Motion of Manufacturing Chemists Association petitioner in No. 78-1988, to file amended petition for review. (Filed in consolidated cases). August 4, 1978 Filing contingent motion of Manufacturing Chemists Association to defer briefing dates on the merits of the liquid mixture exemption amendment to the benzene standard. (Also filed in consolidated cases). August 7, 1978 Filing motion of the American Iron and Steel Institute to file amended petition for review in No. 78-1745. (Also filed in consolidated cases). August 7, 1978 Filing motion of the American Iron and Steel Institute to defer briefing on the merits of the liquid mixture exemption amendment to the benzene standard (Also filed in consolidated cases). August 11, 1978 Order granting motion of the Manufactur- ing Chemists Association to file an amended petition for review; further order granting the contingent mo- tion of Manufacturing Chemists Association to defer briefing on the merits of the liquid mixture exemption amendment to the benzene standard (CC) (Also filed in consolidated cases). 3 August 11, 1978 Order granting motion of the American Iron and Steel Institute to file amended petition for review in No. 78-1745; further order granting motion of American Iron and Steel Institute to defer briefing on the merits of the liquid mixture exemption amend- ment to the benzene standard. (CC) (Also filed in consolidated cases). August 14, 1978 Motion of E. I. Du Pont de Nemours & Co. to file amended petition for review. (Also filed in con- solidated cases). August 18, 1978 Order granting motion of E.I. DuPont de Nemours and Company to file an amended petition for review. October 5, 1978 Opinion and Judgment. THE AMERICAN PETROLEUM INSTITUTE AND THE NATIONAL PETROLEUM REFINERS, ET AL. v. OSHA ET AL., NO. 78-1257 [The relevant docket entries for No. 78-1257 are the same as'for No. 78-1253 except that the petition for review was filed a day later (February 3, 1978) and the docket for No. 78-1257 omits the entries for April 18 and July 7, 1978, shown above for No. 78-1253.] THE RUBBER MANUFACTUERS ASSOCIATION, INC., ET AL. v. EULA BINGHAM, ET AL., NO. 78-1486 March 6, 1978 Petition to review and set aside an order of the Assistant Secretary of Labor for OSHA filed [in the Sixth Circuit, No. 78-3114]. March 9, 1978 Order granting motion of petitioners to transfer this cause to the United States Court of Appeals for the Fifth Circuit. [After transfer, the Fifth Circuit renumbered the case No. 78-1486 and made the following entries :] March 13,1978 Filing order of the Sixth Circuit transferring their docket No. 78-3114 to the 5th Circuit. 4 April 11, 1978 Order granting motion of the Industrial Union Department, AFL-CIO, to intervene. (LRM) (Also filed in 78-1676, 78-1677, and 78-1707). May 5, 1978 Filing respondents’ motion to reschedule argu- ment. Denied JPC. June 22, 1978 Case argued. June 23, 1978 Filing respondents’ letter dtd 6/22/78 with copy of amendments to the benzene standard issued June 27, 1978. (CE) (Also filed in consolidated cases). June 27, 1978 Filing motion of petitioners in Nos. 78-1486 and 78-1677 to file amended petitions for review. June 30, 1978 Filing petitioners’ letter dtd 6/30/78 with “producer” petitioners’ supplemental memorandum which addresses amendment to benzene standard and copy of Federal Register Notice announcing amendment. (CE) (Also filed in consolidated cases). July 7, 1978 Order granting motion of petitioners, the Rubber Manufactuers Association, Inc, et al, and the Armstrong Rubber Company et al, to file amended peti- tions for review. (JPC-CC-GBT) (Also filed in 78-1677). July 11,1978 Filing Secretary of Labor’s motion to adjourn present supplemental briefing schedule, and to set new briefing schedule on the merits of the amendment to the benzene standard. July 14,1978 Order denying the Secretary of Labor’s motion to adjourn present supplemental briefing schedule. Court does not desire briefs designed to enable it to reach the merits of the new standards. (CC). July 24, 1978 Order granting motion of Chemical Speciali- ties Manufacturers Association for leave to intervene (CC). August 4, 1978 Filing motion of Manufacturing Chemists Association, petitoner in No. 78-1988, to file amended petition for review. (Also filed in consolidated cases). August 4, 1978 Filing contingent motion of Manufacturing Chemists Association to defer briefing dates on the merits of the liquid mixture exemption amendment to the ben- zene standard. (Also filed in consolidated cases). 5 August 7, 1978 Filing motion of the American Iron and Steel Institute to file amended petition for review in No. 78-1745. (Also filed in consolidated cases). August 7, 1978 Filing motion of American Iron and Steel Institute to defer briefing on the merits of the liquid mixture exemption amendment to the benzene standard. (Also filed in consolidated cases). August 11, 1978 Order granting motion of the Manufactur- ing Chemists Association to file an amended petition for review; further order granting the contingent. motion of Manufacturing Chemists Association to defer briefing on the merits of the liquid mixture amendment to the ben- zene standard. (CC) (Also filed in consolidated cases). August 11, 1978 Order granting motion of the American Iron and Steel institute to file amended petition for re view in No. 78-1745; further order granting motion of American Iron and Steel Institute to defer briefing on the merits of the liquid mixture exemption amendment to the benzene standard. (CC) (Also filed in consolidated cases). August 18, 1978 Order granting motion of E.I. duPont de Nemours and Company to file an amended petition for review. (Also filed in consolidated cases). October 5, 1978 Opinion and Judgment. E. Il. DU PONT DE NEMOURS & CO. v. OSHA ET AL., NO. 78-1676 March 10, 1978 Petition for review of an order of the Occu- pational Safety and Health Administration, U.S. Depart- ment of Labor, received March 10, 1978, filed [in the Third Circuit, No. 78-1290]. (10 cc) Service attached. March 31, 1978 Order (Aldisert and Adams, C.J.) granting the motions by petitioner for expedited consideration of “petitioner’s Motion for Transfer” and to transfer Peti- tion for Review to the United States Court of Appeals for the Fifth Circuit filed. 6 [After transfer, the Fifth Circuit renumbered the case No. 78-1676 and made the following entries: ] April 3, 1978 Filing Order of the Third Circuit transferring their docket No. 78-1290 to the 5th Circuit. April 11, 1978 Order granting motion of the Industrial Union Department, AFL-CIO, to intervene. (LRM). (Also filed 78-1486, 78-1677 & 78-1707). May 5, 1978 Filing Respondents’ motion to reschedule argu- ment. Denied JPC. June 22,1978 Case argued. June 23, 1978 Filing respondents’ letter dtd 6/22/78 with copy of amendments to the benzene standard issued June 27, 1978. (CE) (Also filed in consolidated cases). June 30, 1978 Filing petitioner’s letter dtd 6/30/78 with “producer” petitioners’ supplemental memorandum which addresses amendment to benzene standard and copy of Federal Register Notice announcing amendment. (CE) (Also filed in consolidated cases). July 11,1978 Filing Secretary of Labor’s motion to adjourn present supplemental briefing schedule, and to set new briefing schedule on the merits of the amendment to the benzene standard. July 14,1978 Order denying the Secretary of Labor’s motion to adjourn present supplemental briefing schedule. Court does not desire briefs designed to enable it to reach the merits of the new standards. (CC) (Also filed in consoli- dated cases). August 4, 1978 Filing motion of Manufacturing Chemists Association, petitioner in No. 78-1988, to file amended petition for review. (Also filed in consolidated cases). August 4, 1978 Filing contingent motion of Manufacturing Chemists Association to defer briefing dates on the merits of the liquid mixture exemption amendment to the ben- zene standard. (Also filed in consolidated cases). 7 August 7, 1978 Filing motion of the American Iron and Steel Institute to file amended petition for review in No. 78-1745. (also filed in consolidated cases). August 7, 1978 Filing motion of American Iron and Steel Institute to defer briefing schedule on the merits of the liquid mixture exemption to the benzene standard. (Also filed in consolidated cases). August 11, 1978 Order granting motion of the Manufactur- ing Chemists Association to file an amended petition for review; further order granting the contingent motion of Manufacturing Chemists Association to defer briefing on the merits of the liquid mixture exemption amend- ment to the benzene standard (CC) (Also filed in con- solidated cases). August 11, 1978 Order granting motion of the American Iron and Steel Institute to file amended petition for re- view in No. 78-1745; further order granting motion of American Iron and Steel Institute to defer briefing on the merits of the liquid mixture exemption amendment to the benzene standard (CC) (Also filed in consolidated cases). August 18, 1978 Order granting motion of E.I. Du Pont de Nemours & Co. to file an amended petition for review. (Also filed in consolidated cases). October 5, 1978 Opinion and Judgment. THE ARMSTRONG RUBBER COMPANY AND UNIROYAL, INC. v. EULA BINGHAM, ET AL., NO. 78-1677 March 6, 1978 Filed Petition for review [in Second Circuit No. 78-4034]. March 27, 1978 Filed Order granting motion to transfer to the United States Court of Appeals for the Fifth Circuit. [After transfer, the Fifth Circuit renumbered the case No. 78-1677 and made the following entries: ] 8 April 3,1978 Filing Order of the Second Circnit transferring their docket No. 78-4034 to the 5th Circuit. [The remainder of the relevant docket entries made by the Fifth Circuit in No. 78-1677 are identical to those beginning April 11, 1978, by the Fifth Circuit in No. 78-1676. ] INDEPENDENT PETROLEUM ASSOCIATION OF AMERICA v. OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, U.S. DEPARTMENT OF LABOR, ET AL., NO. 78-1707 1978 Petition for review filed. [The remainder of the relevant entries for No. 78-1707 are identical to those shown for No. 78-1676 beginning with the entry for April 11, 1978, with the exception that the docket in No. 78-1707 omits the entry for July 11, 1978.] AMERICAN IRON AND STEEL INSTITUTE, ET AL. v. OCCUPATIONAL SAFETY AND HEALTH ADMINISTRA- TION, U.S. DEPARTMENT OF LABOR, ET AL., NO. 78-1745 April 3, 1978 Petition for Review of an order of the Occupa- tional Safety and Health Administration United States Department of Labor, received April 3, 1978, filed [in the Third Circuit as No. 78-1388]. (6 cc) Service attached. April 7, 1978 Order (Aldisert and Adams, C.J.) granting petitioners’ motion for transfer of Petition for Review to the United States Court of Appeals for the Fifth Circuit, filed. [After transfer, the Fifth Circuit renumbered the case No. 78-1745 and made the following entries:] April 10,1978 Filing Order of the Third Circuit transferring their docket no. 78-1388 to the 5th Circuit. {The remainder of the relevant entries for No. 78-1745 are identical to those shown for No. 78-1676, beginning with the eutry for May 5, 1978, with the exception that the docket in No. 78-1745 omits the entry for July 11, 1978. ] 9 MANUFACTURING CHEMISTS ASSOCIATION v. OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, ET AL., NO. 78-1988 March 30, 1978 Petitioner’s petition for review of an order of the Occupational Safety and Health Administration (m-30) [filed in the United States Court of Appeals for the District of Columbia Circuit, No. 1287]. May 5, 1978 Per curiam order granting petitioner’s motion to transfer this case to the Fifth Circuit; Bazelon and Leventhal, CJ’s. [After transfer, the Fifth Circuit renumbered the case No. 78-1988 and made the following entries :] May 8, 1978 Filing order of the District of Columbia Circuit transferring their docket No. 78-1287 to the Fifth Circuit. June 22,1978 Case argued. June 30, 1978 Filing petitioners’ letter dtd 6/30/78 with “producers” petitioners’ supplemental memorandum which addresses amendment to benzene standard and copy of Federal Register Notice announcing amendment. (CE) (Also filed in consolidated cases.) July 14,1978 Order denying the Secretary of Labor’s motion to adjourn present supplemental briefing schedule. Court does not desire briefs designed to enable it to reach the merits of the new standards. (CC) (Also filed in con- solidated cases). [The remainder of the entries for No. 78-1988 are identi- cal to those beginning with August 4, 1978, for No. 78- 1676, except that the docket for No. 78-1988 omits the entry for August 11, 1978, granting motion of AISI to file amended petition and to defer briefing on amend- ment. ] 10 INDEPENDENT PETROLEUM ASSOCIATION OF AMERICA v. OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION ET AL., NO. 78-1989 April 4, 1978 Petitioners’ petition for review of an order of the OSHA (m-4) [filed in the United States Court of Appeals for the District of Columbia Circuit, No. 1308]. May 3, 1978 Per Curiam Order granting Petitioners’ motion for transfer and this case is transferred to the Fifth Circuit: Bazelon and Leventhal, CJ’s. [After transfer, the Fifth Circuit renumbered the case No. 78-1989, and made the following entries:] May 8, 1978 Filing Order of the District of Columbia Cir- cuit transferring their docket no. 78-1308 to the 5th Circuit. June 22,1978 Case argued. July 14,1978 Order denying the Secretary of Labor’s motion to adjourn present supplemental briefing schedule. Court does not desire briefs designed to enable it to reach the merits of the new standards. (CC) (Also filed in con- solidated cases). August 18, 1978 Order granting motion of E.I. Du Pont de Nemours & Co. to file an amended petition for review. (Also filed in consolidated cases) October 5,1978 Opinion and Judgment. November 1, 1978 Order consolidating this appeal with 78- 1253, et al (CC). INDUSTRIAL UNION DEPARTMENT, AFL-CIO v. DR. EULA BINGHAM, ET AL., NO. 78-2642 July 11, 1978 Petitioner’s petition for review of order of the Dept. of Labor (p-10) [filed in the United States Court of Appeals for the District of Columbia Circuit, No. 1644]. July 26, 1978 Per curiam order granting petitioner’s motion to transfer and this case is to be transferred to the USCA for the 5th Circuit as promptly as the business of office permits; CJ Wright and McGowan, CJ. POSTER GS see 11 [After transfer, the Fifth Circuit renumbered the case No. 78-2642 and made the following entries :] August 1, 1978 Filing order of the District of Columbia Circuit transferring their docket no. 78-1644 to the 5th Circuit. August 18, 1978 Order granting motion of E. I. Du Pont de Nemours & Co. to file an amended petition for review. (Also filed in consolidated cases). October 5,1978 Opinion and judgment. November 1, 1978 Order consolidating this appeal with 78- 1253 et al (CC). THE AMERICAN PETROLEUM INSTITUTE AND THE NATIONAL PETROLEUM REFINERS ASSOCIATION, ET AL. v. OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION UNITED STATES DEPARTMENT OF LABOR, ET AL, NO. 78-2779 August 18,1978 Petition for review filed. October 5,1978 Opinion and judgment. THE ADHESIVE AND SEALANT COUNCIL, INC. v. EULA BINGHAM, ET AL, NO. 78-3023 [This case was filed in the Fourth Circuit on August 18, 1978, and transferred to the Fifth Circuit on September 11, 1978. The record does not include the Fourth Circuit’s docket entries but does disclose the filing and transfer dates. After transfer, the Fifth Circuit renumbered the case No. 78-3023, and made the following docket entries :] Sept. 18, 1978 Filing Order of the Fourth Circuit transfer- ring their docket no. 78-1544 to the Fifth Circuit. October 5,1978 Opinion and Judgment. November 1, 1978 Order consolidating this appeal with 78- 1253 et al. (CC). 12 UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT No. 78-1253 THE AMERICAN PETROLEUM INSTITUTE, ET AL., PETITIONERS Vv. OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, RESPONDENTS PETITION FOR REVIEW Pursuant to Section 6(f) of the Occupational Safety and Health Act of 1970, 29 U.S.C. § 655(f), The Ameri- ean Petroleum ‘Institute, the National Petroleum Re- finers Association on behalf of their respective members, and American: Petrofina, Incorporated, Cities Service Company, Continental Oil Company, Delta Oil Company, Exxon Corporation, Gulf Oil Company, Husky Oil Com- pany, Marathon Oil Company, Mobil Oil Corporation, Phillips Petroleum Company, Shell Oil Company, South Hampton Oil Company, Standard Oil Company (Indi- ana), The Standard Oil Company (Ohio), Sun Oil Com- pany of Pennsylvania, Sun Oil Company of Delaware, Texaco Inc., Union Oil Company of California, U.S.A. Petrochem Corporation, and Williams Pipe Line Com- pany, hereby challenge the validity of, and petition this Court for review of, the Permanent Standard for Oc- cupational Exposure to Benzene released by the Occupa- tional Safety and Health Administration, Department of Labor, on February 2, 1978. The Permanent Standard for Occupational Exposure to Benzene challenged by this Petition supplants and replaces the Emergency Temporary Standard for Occu- pational Exposure to Benzene (42 Fed. Reg. 22516) pre- viously challenged by the same petitioners in American Petroleum Institute, et al. v. OSHA, et al., No. 77-1973, presently pending before this Court. 13 By this Petition, the above captioned petitioners also challenge OSHA’s procedural regulations dealing with the official time for issuance of agency actions (29 C.F.R. § 1911.18(d), 42 Fed. Reg. 65166) on the ground that such regulations may be invalid and inconsistent with the D.C. Circuit’s opinion in Industrial Union Dept. AFL-CIO, et al. v. Bingham, et al., Nos. 77-1395, 77- 1516 which retransferred API, et al. v. OSHA, et al. (No. 77-1973) to this Court. Respectfully submitted, Gene W. Lafitte J. Berry St. John, Jr. John M. Wilson of Liskow & LEWIS 50th Floor—One Shell Square New Orleans, Louisiana 70139 (504) 581-7979 Edward W. Warren Robert F. Vanvoorhees Arthur F. Sampson of KIRKLAND, ELLIS & ROWE 1776 K Street, N.W. Washington, D.C. 20006 (202) 857-5000 Counsel for Petitioners February 2, 1978. 14 [The following document was appended to the agency brief in the court of appeals] CARCINOGEN ASSESSMENT GROUP’S PRELIMINARY REPORT ON POPULATION RISK TO AMBIENT BENZENE EXPOSURES This document is being released by EPA for external review Roy E. ALBERT, M. D. Chairman wo ow ais esi aed ~~ = """PARTICIPATING MEMBERS Elizabeth L. Anderson, Ph. D. I. Nathan Dubin, M. D. Richard N. Hill, M.D., Ph. D. Robert E. McGaughy, Ph. D. Lakshmi C. Mishra, Ph. D. Ruth Pertel, Ph. D. Wade T. Richardson, J. D. Todd W. Thorslund, Se. D. STAFF ASSISTANT Claudia Slacik sia aol LS re ote 15 [Table of Contents Omitted in Printing] PRELIMINARY ESTIMATE OF POPULATION RISK TO AMBIENT BENZENE EXPOSURES I Summary There is substantial epidemiological evidence that ben- zene is a human leukemogen. However, no validated ani- mal model has yet been developed for benzene as a car- cinogen. There are several large series of case reports indicating a high risk of leukemia in individuals who developed aplastic anemia consequent to benzene expo- sure. In addition there are a number of epidemiological studies in the rubber and shoe industries that demon- strate an excess risk of leukemia. From the standpoint of making quantitative estimates of the leukemia risk - “associated with current general population exposures to benzene in the United States there are only two epi- demiological studies that provide some estimates of both exposure to benzene and data on the occurence of leu- kemia. These studies are by Infante (3) and by Ott, et al. (5). The Infante study, which showed an excess incidence ia, is not yet completely analyzed. Hence, some (ptions have had to be made about the average dura- and magnitude of exposures. For this reason, this w#eport should be considered as preliminary. The Ott f study indicated no excess leukemia risk with relatively - well-documented exposures. The results of the Infante study were used as the basis for an extrapolation of the leukemia risk to the low levels of general population exposure, which averages one part per billion (4). A linear non-threshhold model was used for the extrapolation; such a model is expected to give an upper limit to the estimated risk. Using this extra- polation model, and using the leukemia rates observed in the cohort of workers exposed to benzene over a period of about 30 years (in the Infante study), we estimated that the number of cases of acute myelogenous and my- onocytic [2] leukemia per year in the general population \ 16 due to ambient atmospheric benzene is somewhere be- tween 30 and 80 cases. The lifetime risk to an individual continually exposed to benzene at a level of 1 ppb is estimated to be between 10° and 2.5 x 10°, depending on which exposure assumptions are made in the Infante study. The risk from individual sources of benzene emis- sions ranges from about 10° to 5 x 10°. The Ott study, which reported no excess leukemia risk, is consistent with the Infante study on statistical grounds given their rela- tive exposures. However, the negative results of the Ott study suggest that the level of calculated risk in the general population is not likely to be higher than 10° to 2.5 x 10°, but it could be lower. [3] II Introduction The Carcinogen Assessment Group (CAG) has been asked by the Office of Air Quality Planning and Stand- ards (OAQPS) to estimate the carcinogenic risk to the United States population of ambient benzene concentra- tions. This type of information is useful in judging the overall contribution of benzene emissions to the national rates of cancer mortality, and will be used by OAQPS in the decision whether to regulate benzene. As the primary basis for this estimation the CAG is using the Infante (Infante, et al. 1977) mortality study of workers exposed to benzene in the production of a natural rubber cast film product. The reasons for this choice are: (1) the worker exposures are said to have _been almost exclusively restricted to benzene, since it is used throughout the plant as the principal solvent in all major processes; (2) the individuals in the cohort all worked before 1950 and were followed until 1975, thus allowing long latency diseases to be observed and (3) acute myelogenous leukemia was observed, which is the same cell type of leukemia observed in other studies where workers have had known benzene exposures. The disadvantages of relying on this study for determining general population risks are (1) the authors essentially give no estimate of worker exposures except to say that the levels were less than the prevailing recommended oc- 17 cupational limits at the time various monitoring surveys were made; (2) the cohort studied actually worked at two separate plants (Akron and St. Mary’s, Ohio). Air monitoring information in the former plant is almost non-existent (Baier, 1977), and therefore the exposure to half of the members of the cohort is almost completely unknown. However, it is known (Young, 1977) that the crude rates (leukemia cases/total people in the cohort) are similar in the two [4] lecations; (3) Warren et al. (1977) have claimed that over 400 workers known to be exposed to low benzene levels were deliberately excluded from the cohort. In spite of these difficulties the Infante study is the only one currently available which reports an excess rate of leukemia among benzene-exposed populations. Another occupational study (Ott, et al. 1977) of workers exposed to benzene has documented the exposures relatively well and reports no excess leukemia risk. The risk estimates based on Infante’s study are used to calculate the num- ber of cases expected in the cohort examined by Ott, et al. If this is not significantly different than the observed number of cases, the estimates are not grossly in error. A more complete evaluation of the Infante study will be possible after the authors have made a final evaluation of their data. , III. Description of Infante Study In a retrospective study of mortality among a cohort of 748 white male workers in two Ohio plants manufac- turing a natural rubber cast film product, Infante, et al. (1977) observed a statistically significant higher rate of leukemia than both of two control groups. The leukemia mortality rate was 5.06 times higher than the general U. S. white male population standardized for age and time period of the cohort exposure, and 4.74 times higher than a cohort of 1447 white males employed at an Ohio fibrous-glass construction products factory. These results were based on a 75% follow-up of the vital status of the workers. A total of 160 deaths were observed and of these there were 7 leukemia deaths four of which were 18 acute lyelogenous, one chronic myelogenous, and two monocytic leukemia. The worker exposure information is discussed in IV B below. [5] IV. Analysis of Myelogenous and Monocytic Leu- kemia Risks due to Benzene Exposures A. General Approach As was noted in the benzene health document (Gold- stein, et al. 1977), very little information exists that can be utilized to obtain a dose response relationship be- tween benzene and leukemia in humans or animals. However, if a number of simplifing assumptions are made, it is possible to construct a crude dose response model whose parameters can be estimated using vital statistics, the Infante study, historical benzene workplace standards, and a recent environmental benzene exposure study. (Mara and Lee, 1977) We assume that for low exposures the lifetime prob- ability of death from leukemia may be represented by the linear equation P=a+ px where a is the rate in the absence of benzene exposure and x is the average lifetime exposure to atmospheric benzene expressed in ppm. The term § is the change in the leukemia rate for each increase of one ppm of ben- zene in the air. From the Infante, et al. study the relative risk of leukemia for benzene workers compared to the general population was obtained. We will denote this ratio as R and niake the assumption that R= R,=a+ B(x, +x,) R, a+ BX, where x, is the exposure of the general population to benzene and x, is the industrial exposure to benzene. 19 [6] From our two assumptions we have the two linear equations in two unknowns of the form RR,=a~+ Bx, + BX, R,=a~+ Bx, so that B=R, (R-1) /x, and 8 x, is the average lifetime risk due to ambient benzene exposures. To utilize this technique to predict risk it is necessary to obtain estimates of R,, R, X,, and X.. The estimation of each of these quantities is discussed in a separate section. B. Estimation of Relative Risk R Infante, et al. (1977) established as a lower bound a total of seven acute myelogenous or monocytic cases of leukemia in their studied cohort of 748 members. They calculated an expected value of 1.3831 cases for all forms of leukemia. From the 1971 U.S. Vital Statistics (U. S. DHEW, 1971) we note that of 7,564 cases of leukemia in white males, a total of 3,260 or 43% were myelogen- ous or monocytic. Thus an estimate of the relative risk for acute myelogenous and monocytic leukemia in white males is 7 R= 1.3831 x0.43=11.77 [7] C. ESTIMATION OF BACKGROUND LEUKEMIA RATE R, The lifetime risk to a disease can be estimated from age-specific deaths rates in the following manner. We assume that during different segments of a lifespan the total and disease specific death rates are constant. we define the following terms: aj=death rate due to a specific disease during the jt life- time segment. aj+ \j=total death rate during jt* lifetime segment. S; length of j* lifetime segment. => 20 P,,=- ., = = probability of death due to the specific diseaes 4 aj*AJ given that death occurred during the jt life- time segment. P,,=1-e-(aj +Aj)S,= probability of death during the j® lifetime segment given survival up to the start of the jt lifetime seg- ment. Posed 1-P,,.) = probability of survival until the start of k= the j' lifetime segment. If we assume that the entire lifetime is divided into m mutually exclusive segments then by definition P;,—1, P.m==1 and the entire lifetime probability of the disease is m P=> P,; P.; Ps; j=1 [8] The age specific rates for white males for myelo- genous and monocytic leukemia were estimated from the total leukemia rates by multiplying the entries in Table I-13, disease categories 204-207, white male (U. S. DHEW, 1971) by 0.43. This gives the entries j} shown in Table 1. The total mortality aj + Aj is also obtained from table I-13 and is shown in Table 1. The other terms are calculated by the given definitions and the final result, the lifetime risk of white males exposed to background levels of benzene is found to be R, =0.38987 x 102 TABLE 1 [9] COMPUTATION OF LIFETIME RISK OF MYELOGENOUS-MONOCYTIC LEUKEMIA .0000072_ .0000659 .0001348 .0000920 .0000983 .0001287 .0002287 .0005061 .00095 10 .0011108 0005752 Xs .0038987 aj aj + Aj Sj Age Intervals rE .9816 2 9785 9745 — 9621 9473 .9184 .8556 .7268 .5078 - -+- #+¢§ = + + .3940x10-* 1,852.8 73 1.68 1.38 .2111x10" 79.6 1-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 74-85 85+ 4042x10- 3407x100" 40.5 127.6 155.4 309.6 10 10 10 10 10 10 10 10 .7445x10 95 1.03 1.38 2.58 6.41 15.57 31.43 43.65 .6628x10- .3049x10- 4457x107 .3640x10-2 708.7 1,632.0 3,586.1 .15058 30135 53919 3928x107 4342x107 4057x107 7,747.6 17,758.1 .2340 .2458x10 R, =0.0038987 22 [10] D. ESTIMATE OF AVERAGE AMBIENT BEN- ZENE EXPOSURE In a recent EPA contractor report (Mara and Lee, 1977), data relating to benzene exposure in the United States was compiled. For each of several annual average concentration ranges, the population exposed to seven categories of benzene emissions was calculated. The seven categories were: (1) chemical manufacturing, (2) coke ovens, (3) gasoline service stations (separately for peo- ple using self-service stations and for people living in the vicinity of the stations), (4) petroleum refineries, (5) solvent operations, (6) storage and distribution of ben- zene and (7) urban exposures related to automobile tail- pipe and gasoline tank emissions. The general procedure used was to start with production data for benzene or its major products, estimate emission factors (benzene re- lease per kg of end product), apply an appropriate air dispersion model to obtain concentrations as a function of distance from the source, and to use population density information for each location to calculate the number of people exposed to each concentration range. Air monitor- ing data were used whenever it was available. The re- sults are summarized in Table 2. From this data one can calculate that the annual average exposure of an indi- vidual to ambient benzene from all sources is 1.03 ppb. TABLE 2. [11] SUMMARY OF POPULATIONS EXPOSED (THOUSANDS) TO ATMOSPHERIC BENZENE EMISSIONS ¢ Gasoline Stations Urban Solvent Operations Exposures Petroleum Vicinity Refineries Coke Self Mfg. Ovens Service Chem. Total Population (ppb) Concen- trations 0.042 0.50 37,000 7,497 15,726 87,000 6,529 208 68,337 45,353 37,000 185,297 23 31,000 301,684 0.5404 0.042 0.7627 0.5112 0.5465 0.8989 2.0885 0.7514 Population Weighted Averages (ppb) Average exposure to the population of 220 million is 0.7514 x 301,684=1.030 ppb 220,000 * Adapted from Mara and Lee (1977). 24 [12] E. ESTIMATION OF AVERAGE OCCUPATION- AL EXPOSURE Information about the plant benzene levels is contained in the Appendix to the testimony of Baier at the OSHA benzene hearings (Baier, 1977). From the opening of the factory in 1940 until 1946, no monitoring records were available. Following the in- stallation of new ventilation equipment in 1946, a survey showed that “most areas” in the plant ranged from 0 to 15 ppm and that all areas were less than the maximum safe limit of 100 ppm which prevailed at that time. From this information, one can guess that the average expo- sure to all people in the plant before 1946 is probably not much more than 100 ppm, and not less than 15 ppm. Benzene levels were monitored after 1946 at various plant locations but they were all instantaneous samples and no reliable information is available about how many man-hours were spent at those locations or whether pro- tective masks were worn. These are case reports of ex- posures of 1000 ppm for short time intervals. Since the average levels were generally close to the occupational standard, we will make the assumption that the average worker exposure was the same as the prevailing recom- mended occupational limits. These are tabulated below along with the time weighted average for the 36 years of the total exposure period. Time Average Time-Weighted Interval Exposure( ppm) Average(ppm) 1940-46 (7) 100-15 1947 (1) 50 39.9-23.3 1948-56 (9) 35 1957-68 (12) 25 1969-1975 (7) 10 [13] The actual levels to which the workers were ex- posed was a subject of heated debate at the OSHA ben- zene hearings. The CAG would like to see a realistic es- timate of the population weighted average exposure and its uncertainty limits. The time-weighted averages for occupational exposure must be converted to a continuous exposure life-time basis. It will be assumed that the 25 maximum likely lifetime exposure would result if a work- er entered the factory in 1940 and was exposed to 82 ppm for 10 years and 23.7 ppm for 25 years (which is equiva- lent to an average of 40.36 ppm for 35 years) and the least likely exposure would occur if a worker started in 1950 and was exposed to 23.7 ppm for 25 years. There- fore the equivalent continuous lifetime exposures are: High estimate: 40.36 x 240 x 1x 35=4.4 ppm 865 3 70 Low estimate: 23.7 x 240 x 1x 25=1.8 ppm 865 3 70 [14] F. CONCLUSIONS Given the following derived estimates of our para- meters of interest: R =11.77 R, = 0.38987 x 10~ X, =1.030 x 10-** ppm X,=1.8 to 4.4 ppm the parameter @ and the resulting lifetime risks and ex- pected number of acute myelogenous and monocytic leu- kemia deaths can be derived in_the manner previously indicated. In table 3 the average risk rates and expected number of cases per lifetime and per year are shown for total benzene exposure. In Table 4 the total rates and cases are subdivided by source of exposure. We note that about 85% of the total number of cases are directly re- lated to the use of gasoline. It should be emphasized that due to the very crude methods that were necessarily employed in the estima- tion of benzene exposures by both CAG for Infante’s cohort and Mara and Lee (1977) for the U.S. population, the estimates could easily be in error by several orders of magnitude. This is true even if the form of the mathe- matical response model used is a correct rescription of benzene induced leukemia, which is also open to question. However, an additional independent negative study of workers exposed to benzene (Ott, et al. 1977, Dow Chemi- 26 cal Company) can be used to ascertain whether our model, based on Infante’s data, grossly over-estimates the leukemia risk to benzene exposure. They reported the mortality [15] experience of a cohort of workers whose exposure to benzene had been carefully documented since 1940. No excess of leukemia was observed in the cohort by 1973. Since the prediction model was previous- ly discussed based upon workers with highly uncertain exposures, it was felt to be important to estimate the number of leukemia cases we might expect in Dow’s cohort if our model was valid. Using Dow’s exposure estimates and expected number of cases for its workers, it was found that our model predicted from 1.43 to 1.74 cases of leukemia where one case was actually observed. Since this estimate is well within the limits of normal statistical variability we can be confident in claiming that the Dow study does not of- fer any evidence upon which to question the validity of our model. of Expected Number Cases/Year Lifetime Exp. Leukemia Cases in U.S. 2.177 .. 5,436 TABLE 8 TOTAL U.S. POPULATION RISKS TO BENZENE Average Risk BX, .9897x10-" .2471x10~ .4149x107/X, .9609x107 .2399x10" B 4.4 ppm 1.8 ppm (X,) Industrial Exposure * This represents about 1.2% of cases observed in 1971. [16] High Low 1.8 499 211 37 81 2,456 **5 449 X, 85 15 865 32 1.2 982 Lifetime Expected 200 of Leukemia Cases X,=4.4 **2,180 X,=1.8 5.00x10°° 1.30x10-° 1.01x10* 1.83x10-° 1.23x10-° 1.35x10° 2.16x10-° Risk Rates TABLE 4. X,=4A4 2.x10° 5.19x10* 4.04x10° 7.33x10-° 4.91x10°° 5.41x10-° 8.64x10° 9.98 16.30 37.00 22 118.00 6.60 Population Exposed 220.00* 113.69 * Does not sum due to multiple exposure. Average Level of Exposure ppb. Millions 2.0885 5404 .042 .7627 5112 5465 8989 1.030 EXPOSURE FOR DIFFERENT SOURCES ~- Source of Exposure ** This represents about 1% of the number of cases expected in a lifetime assuming current incidence rates. RISK AND LIFETIME EXPECTED NUMBER OF LEUKEMIA CASES DUE TO BENZENE Self-Ser. Gas Vicinity of Gas Stations Petroleum Refineries Solvent Operations Urban Exposures Coke Ovens Stations Chem. Mfg. Total [17] 29 [18] REFERENCES 1. Baier, E. J. “Statement of the National Institutes of Occupational Safety and Health’, Exhibit 64A, OSHA Benzene Hearings, July 19-Aug. 10, 1977. 2. Goldstein, B. D., C. A. Snyder, R. Snyder, R. and S. R. Wolman, “Review of Benzene Toxicity,” pre- pared for EPA, August 18, 1977. 3. Infante, P. F., J. K. Wagoner, R. A. Rinsky, R. J. Young, ‘Leukemia in Benzene Workers,” Lancet, p. 76-78, July 9, 1977. 4. Mara, S. J. and Lee, S.S., “Human Exposures to At- mospheric Benzene” EPA contract 68-01-4314 with Stanford Research Institute, September, 1977. 5. Ott, M. G., J.C. Townsend, W. A. Fishbeck, R. A. Langner, “Mortality Among Individuals Occupation- ally Exposed to Benzene” Exhibit 154,,OSHA Ben- zene Hearings, July 19-August 10, 1977. 6. U.S. Department of Health, Education and Welfare. “Vital Statistics of the United States, 1971, Volume II-Mortality, Part A’, Superintendent of Documents, U.S. Government Printing Office, Stock No. 017-022- 00378-3. Warren, E. W., R. F. Van Voorhee, A. F. Sampson, “Post Hearing Brief of API, NPPA, and Individual Member Companies Regarding the Proposed Revised Permanent Standards for Occupational Exposure to Benzene”, OSHA Docket No. H-059 September 22, 1977. Young, R. J. National Institute of Occupational Safe- ty and Health, Personal Communication, October, 1977. 39 [The following document was attached to the reply brief of the American Petroleum Institute in the Court of Appeals] AFFIDAVIT OF DR. STEVEN H. LAMM I, Dr. Steven H. Lamm, being duly sworn, do state and depose as follows: 1. I was graduated from the University of Southern California in 1968 with the degree of Doctor of Medi- cine. From 1968 to 1969, I held a rotating internship at the University of-Oregon. From 1969 to 1970, I held a residency in pediatrics at the Montreal Children’s Hos- pital. From 1970 to 1972, I was employed by the United States Public Health Service as an epidemiologist at- tached to the Connecticut State Department of Health. From 1972 to 1973, I was Senior Pediatrie Resident at the Bronx Memorial Hospital, Albert Einstein School of Medicine. From 1973 to 1974, I attended the London School of Hygiene and Tropical Medicine, in London, England. From 1974 to 1976, I was Senior Epidemiolo- gist at the National Institute of Child Health and Human Development of the National Institutes of Health. From 1976 to 1977, I was in private practice as a pediatrician and as a consultant in epidemiology. From 1977 to the present time, I have been an associate with Tabershaw Occupational Medicine Associates. 2. I appeared as a witness for the Manufacturing Chemists Association during the hearing held last sum- mer by the Occupational Safety and Health Administra- tion (OSHA) on the proposed standard for occupational exposure to benzene. In the course of preparing my testimony and attending the hearing, I became thoroughly familiar with the evidence associating occupational ex- posure to benzene with leukemia, particularly the study conducted by Infante, et al.’ 3. In December of 1977, I prepared and presented to the Environmental Protection Agency’s Science Ad- 1 Infante, Rinsky, Wagoner & Young, Lewkemia Among Workers Exposed to Benzene (April 28, 1977) (OSHA Exhibit 40). SELLA RPM te phe ED 2 ne a ee ° 31 visory Board a review and critique of the preliminary report by EPA’s Carcinogen Assessment Group (CAG) entitled “Population Risk to Ambient Benzene Expos- ures.” * I have the following comments on the CAG re- port as it compares to the risk estimate developed by Dr. Richard Wilson, presented to OSHA during the 1977 benzene hearing.* I have reviewed and am thoroughly familiar with both documents. 4. In its brief filed in the above-captioned case on June 8, 1978, OSHA cites the CAG’s preliminary find- ings of 30-80 cases of leukemia from exposure to ambient levels of benzene as discrediting Dr. Wilson’s analysis, which concluded that OSHA’s 1 ppm standard will pre- vent, at most, 2 cases of cancer every six years.‘ OSHA’s use of the CAG estimates, which are based on the lifetime continuous exposure of a population of 220 million people, is specious and seriously misleading as applied in the occupational context. I have performed a series of cal- culations (See Exhibit A) which show that the CAG’s risk estimate, when translated to the occupational con- text, is fully consistent with—indeed, somewhat lower than—Dr. Wilson’s estimate. 5. The CAG and Wilson estimates are based on risk estimates of two different populations with two different sets of exposure assumptions. The CAG estimate of 30- 80 cases is an estimate of the number of cases of acute non-lymphocytie leukemia deaths that might occur an- nually if the USA total population of 220 million people were exposed continually throughout their lifetime, 24 hours a day, 365 day a year, to a benzene concentration of one part per billion in air. 6. The Wilson estimate of one leukemia case and one additional cancer case in 6 years is based on the assump- tion that for a year 30,000 workers exposed to benzene at a level between 1-10 ppm are exposed 8 hours, 240 working days a year at an average level of 3 parts ner 2The CAG Preliminary Report is attached as Addendum C to OSHA’s brief filed on June 8, 1978 in the above-captioned case. 3’ Testimony of Dr. Richard Wilson, Ex. 149.B. * OSHA Brief 87 n.80. 32 million benzene in the air. The figure of 30,000 is ob- tained from page 1-7 of the Economic Impact Study of the proposed standard prepared by OSHA by Arthur D. Little, Inc. 7. In order to compare these estimates, they must be related to the same exposure level and time and to the same population. CAG indicates that their case numbers are based on an estimation that the lifetime (70 year) risk of leukemia due to lifetime (70 years), continuous (24 hours/day, 365 days/year) exposure to 1 ppb ben- zene in air is from 1 x 10° to 2.5 x 10°. Wilson’s case numbers derive from the assumption that 1.8 x 10° is the yearly risk of a worker dying from leukemia from having been exposed for one work year of 8 hours/day, 240 days/year to a level of 1 part per million benzene. Attached Exhibit A reviews the algebra necessary to com- pare the two estimates. 8. Assuming an average lifetime of years, Equation 2 divides the CAG risk by 70 and identifies the lifetime risk for 1 year, continuous exposure to 1 ppb of benzene as [from 0.14 to 0.36] x 10, or [from 140 to 360] x 10°. In Equation 3, I again divide by 70 to produce the annual risk of 1 year, continuous exposure to 1 ppb of benzene, which is [from 2.0 to 5.1] x 10°. 9. Workers do not work 24 hours a day, which is the exposure period assumed in the CAG model, but generally work only one-third of a day (8 hours). Therefore, Equa- tion 4 divides the CAG risk by 3, to produce a risk of [from 0.7 to 1.7] x 10°, as the annual risk for 1 year of eight-hour daily exposure to 1 ppb of benzene. 10. In addition, the CAG estimate assumes exposure every day of the year, but workers do not work every day. Therefore, weekends, holidays and _ vacations, amounting to about one-third of the full year, must be excluded. Equation 5 accomplishes this, and shows an annual risk for 1 work-year of eight-hour workday ex- posure to 1 ppb [from 0.45 to 1.1] x 10°. 11. Finally, the CAG assumes exposure to 1 part per billion of benzene. To obtain the risk of exposure to 1 5 CAG Preliminary Report, Table 3. 33 part per million of benzene, the risk must be multiplied by a factor of 1000, and Equation 6 reveals that, based on the CAG’s risk estimate, the annual risk of 1 work year of eight-hour workday exposures to 1 part per mil- lion of benzene is [from 0.45 to 1.1] x 10”. _12. Thus it is shown that CAG’s estimate of lifetime risk of acute non-lymphocytic leukemia (ANLL) death of [1.0 to 2.5] x 10° for lifetime continuous environ- mental exposure to 1 ppb benzene is equivalent to a [0.45-1.1] x 10° annual risk of ANLL death for 1 year of occupational exposure (8 hours/day, 240 days/year) to 1 ppm benzene. 13. Dr. Wilson has based his case count on an annual risk of death from all types of leukemia (not just ANLL) of 1.8 x 10° for one work year of occupational exposure to 1 ppm benzene. Since only 43% of leukemia deaths are due to acute nonlymphocytic leukemia, the Wilson risk can be translated into a 0.77 x 10° risk of acute non- lymphocytic leukemia death from one work year of oc- cupational exposure to 1 ppm benzene. 14. Thus, Wilson and CAG have reached the same estimate of the annual risk of acute non-lymphocytic leukemia death due to one work year of occupational exposure to 1 ppm benzene, to wit, CAG estimate = [from 0.45 to 1.1] x 10° Wilson estimate — 0.77 x 10° 15. Based on the data provided in the Arthur D. Little Study, Dr. Wilson assumed that the 30,000 workers exposed to between 1 and 10 ppm are exposed to an average of 3 ppm benzene. It therefore follows, using the CAG estimate, that a reduction in these workers’ ex- posure to benzene from 3 ppm to 1 ppm might reduce “sg ANLL mortality annually for each year of exposure y (0.45 to 1.1 x 10°) x (1 work year) x (3 ppm-l ppm) x (30,000 people) = ([0.45 to 1.1] x 10°) x 1 x 2 x 30,000 = (.027-.066) cases ANLL/year. = one case every 15-3714 years Use of the Wilson estimate of .77 x 10° would predict 046 excess cases ANLL each year or 1 case every 21 years. 34 16. Wilson’s estimate of one leukemia case and one other cancer case in 6 years was based on three addi- tional conservative assumptions. a. All leukemias (not just ANLL) are benzene re- lated. b. For every benzene leukemia there would be an- other cancer at another site in the body due to benzene exposure. ce. Benzene exposure of those currently exposed to 1 to 10 ppm benzene would be far less than 1 ppm if a new standard were introduced. There is no reason to believe the need for any of these pessimistic assumptions, but these assumptions account for the different numbers derived from the Wilson risk estimate. 17. It is concluded, based on the CAG estimate and its underlying assumptions, that reduction of occupa- tional benzene exposure from 10 ppm to 1 ppm for each year of work might reduce the annual mortality for acute non-lymphocytic leukemia by 1 case every 15-38 years. 18. The CAG estimated range was based on the premise that the Infante cohort was exposed to a mean occupational exposure of 24-40 ppm benzene. This was based on the assumption that the exposure was at the maximum permissible exposure level in effect from time of hire in the forties to the end of study period 1975. This assumption leads to an under-estimation of the levels of exposure because: 1) industrial hygiene data show that nearly half the surveys indicated levels greater than the TLV at that time; and 2) the inclusion of exposure estimates through 1975 is inappropriate since all the leukemia deaths occurred prior to 1962 and the period of exposure necessary to inclusion in the study ended in 1949; and 3) the estimate ignores exposures prior to 1941 when no maximum exposure standard existed and during which many employees worked. Evidence in the hearing indicated that levels of exposure exceeded 100 ppm in the forties.’ If the CAG estimates was recal- ® See Brief of API, AISI, MCA and IPAA, the printed version of which was filed in the above-captioned case on June 13, 1978, at pp. 15-18, 26-37. 35 culated under the assumption that the exposure was at 100 ppm (rather than 24 or 40 ppm), the risk estimate would be further reduced by 60% to a risk estimate of about 0.20 x 10°, which would predict that OSHA’s 1 ppm standard would avoid .012 cases ANLL per year, or about one case in 83 years. 19, The purpose of this exercise has been to indicate the similarity between the risk estimates produced by CAG and by Dr. Wilson. My purpose has not been to prepare a new, independent estimate of the effect of OSHA’s standard. As indicated by CAG’s acknowledge- ment that its risk estimate may be off by several orders of magnitude, risk estimates are necessarily imprecise because of the large number of variables (such as eXpos- ure levels, non-occupational exposures, etc.) for which accurate information is not available. Nonetheless, it is encouraging that the two different attempts to conserva- tively address these issues compared here have reached results so similar. STEVEN H. LAMM 36 EXHIBIT (1) [1.0 to 2.5] x 10-5 (2) [10 to 25] x 10 70 (3) [140 to 360] x 10° 70 (4) [2.0 to5.1] x 10-° 3 (5) 240 x [0.7 to 1.7] x 10° 365 (6) [0.45 to 1.1] x 10-® x 108 A [10 to 25] x 10-° CAG estimate of lifetime risk of lifetime, continuous ex- posure to 1 ppb of benzene [0.14 to 0.36] x 10-° 140 to 360 x 10-° lifetime risk for 1 year, con- tinuous (24 hour) exposure to 1 ppb [2.0 to 5.1] x 10-° annual risk for 1 year, con- tinuous (24 hour) exposure to 1 ppb [0.7 to 1.7] x 10-* annual risk for 1 year, 8 hour daily exposure to 1 ppb [0.45 to 1.1] x 10-° annual risk for 1 work year of 8 hour, workday exposure to 1 ppb [0.45 to 1.1] x 10-6 annual risk for 1 work year of 8 hour workday exposure to 1 part per million 37 UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT Nos. 78-1253, 78-1257, 78-1486, 78-1676, 78-1677, 78-1707, 78-1745, 78-1988, 78-1989, 78-2642, 78-2779, © and 78-3023 OSHA No. 77-1395 Before Coleman, Clark and Tjoflat, Circuit Judges. JUDGMENT These causes came on to be heard on the petitions of the American Petroleum Institute, et al., and were ar- gued by counsel; ON CONSIDERATION WHEREOF, It is now here ordered and adjudged by this Court that the petitions for review of an order of the American Petroleum Institute, et al., in this cause be, and the same are hereby granted; the provisions of the order reducing the airborne permissable exposure limit and the dermal contact prohibition are set aside and the remaining pro- visions of the standard in this cause be and the same are hereby vacated. It is further ordered that respondents pay to peti- tioners the costs on appeal to be taxed by the Clerk of this Court. October 5, 1978 Issued As Mandate: 38 SUPREME COURT OF THE UNITED STATES No. 78-911 INDUSTRIAL UNION DEPARTMENT, AFL-CIO, PETITIONER Vv. AMERICAN PETROLEUM INSTITUTE, ET AL. ORDER ALLOWING Cermionady) Filed February 21, 1979 The petition herein for a writ of certiorari to the United States Court of Appeals for the Fifth Circuit is granted. The case is consolidated with No. 78-1036 and a total of one hour is allotted for oral argument. 39 SUPREME COURT OF THE UNITED STATES No. 78-1036 RAY MARSHALL, SECRETARY OF LABOR, PETITIONER | v. AMERICAN PETROLEUM INSTITUTE, ET AL. ORDER ALLOWING CERTIORARI. Filed February 21, 1979 The petition herein for a writ of certiorari to the United States Court of Appeals for the Fifth Circuit is granted. The case is consolidated with No. 78-911 and a total of one hour is allotted for oral argument. 40 [The following testimony is from the reporter’s transcript of the rulemaking hearing on the proposed benzene standard] * * * * [859] MR. JACOBSON: Thank you. One other ques- tion here and that is the employes that were cited here had considerable dermal exposure as well as exposure in the working atmosphere as far as inhalation. Does any- one on the panel have any feeling as to whether this dermal exposure is a contributing factor or [860] is the addressing of the dermal problems with benzene in this proposed standard for problems other than leukemia. DR. DOUGLAS SMITH: I can start it off and then if someone wants to continue it a little bit, they can. Yes, the problem of dermal absorption is, I think, real. Benzene in relation to other aromatic materials, by com- paring it let’s say to toluene and xylene. Apparently it is not absorbed through the skin at the same rate as toluene and xylene but it nonetheless can be absorbed. Even if you take and have a situation in which you have got an inflamed skin or some abnormal situation, or if you have got it contained in a mixture, I| believe that a considerable amount can be absorbed. I believe that this has been demonstrated in the past with meas- urements of urinary phenol from dermal absorption of benzene. We don’t consider that it is absorbed as a clear com- pound extensively. It can be. - MR. BAIER: Maybe Blair or ;Bob would want to dis- cuss it from a medical standpoint» . DR. LAIGO: Well, it can be absorbed through the skin, it is readily absorbed through -the skin. To what extent it would be absorbed in any. particular exposure, you don’t really know. You can’t mesure that. It cer- tainly is a significant thing and if pele are getting it on their skin, it certainly could be signi¥icant. * * * «A [2104] MR. WARREN: Dr. Zachauses? DR. ZACHAUSER: I am Richard | fessor of Political Economy at Harvard | achauser, Pro- niversity. My 41 fellow witnesses have testified on the adequacy and in adequacy of the Arthur D. Little report. I will not focus on that for two reasons: [2105] First, I think that the Arthur D. Little Company, assuming that it was at all responsive to its assigned task, was given the wrong task. Second, I don’t think that the findings of the Ar- thur D. Little study, whatever they might reasonably have been, would likely have influenced the final deci- sions that OSHA would make. This suggests that we are in an unfortunate position where analysis is not employed to affect decision making, but might be thought of more as a charade. Let me discuss the way an economist looks at this problem, indeed, at any problem. The science of econom- ics is basically devoted to a very simple problem. How should we allocate resources to competing objectives. With this problem there are two objectives: One is to have economic resources available to accomplish other purposes. The second one is to promote human health. The economic resources that are involved here are quite substantial accepting on face value the Arthur D. Little report. We are talking about $267 million worth of capital costs, $124 million worth of first year operat- ing costs, $76 million of continuing operating costs. At any reasonable rate of discount, this is a $1 billion deci- sion. It would be reasonable to ask, under the circum- stances, what are we accomplishing? What are we buy- ing for our $1 billion expenditure or rather, what are the people who are being forced to spend their money buying for their $1 billion expenditure. [2106] We have a little bit of information in the Ar- thur D. Little report. For example, we know that there are 30,000 who are at risk levels above one part per million. We do not know, however, what happens to these 30 thousand workers. We know they are to be moved below a standard, but we don’t know whether we are getting rid of 20 cases of leukemia, 10 cases of leu- kemia, one case of leukemia, the expected vaiue of .001 cases of leukemia. I think that information is obviously vital to our decision making process. The objection might be raised that we do not want to put a price tag on human lives. OSHA has continually 42 maintained that there is no legitimate procedure for put- ting a price tag on human lives and I wouldn’t disagree with that. I would say that we want full information so that people in authority in the decision making process will be able to see what trade off they are making. Basically to adopt the notion that we don’t have to quantify the health benefits. Not just saying that there are health benefits, however small. There was testimony earlier that they might be non existent. To say what the actual health benefits are, I think, is essential and to argue the contrary is to say that ignorance is better than knowledge. I think that is not a very sensible thing to do. Is there anything that we can do where we don’t want to put a price tag on human lives? I think the answer is [2107] yes we can try to follow what economists refer to as a cost-effectiveness approach. Basically, for what- ever resource dollars we are going to spend for promot- ing health, we try to achieve the maximum level of bene- fits. In order to do this, you have to know what benefits are going to come out of that type of expenditure. All the time we are incurring risks because we think we get other benefits. We let people drive cars even though we know that if we put the speed limit down 20 miles pe. «r., we would have fewer accidents. At zero miles per ‘cur, we would have no accidents. We allow people to ec ich desserts, live in wooden houses instead of brick houses which would be safer and I would say in all of these areas the level of risk, even if you make the most exagerated estimate of the leukemic affect of the exposure to benzene and other health consequences are much greater than the ones we are confronting here today. I say also that the government in its regulatory proc- esses is getting into this problem in a very major way. I was reading the Washington Post this morning and there was an article on what is called CAT scanners, computer assisted tomography which is a sophisticated diagnostic technique that assists in various medical pro- cedures. The Federal government is presently getting into the position of regulating the use of these scanners 43 not that it doesn’t help in an occasional instance to diag- nose a very difficult disease, but the benefits in terms of improved diagnosis and medical treatment aren’t worth the cost. [2108] Here we know what the costs are, or at least we know one estimate of costs. We have no notion of what the benefits are. I should say, by the way, that other areas of government have followed the approach of putting a price tag on human lives. For example, the National Highway Traffic Safety Administration which is responsible for such things as tire standards or air bags, uses a figure of $250,000 per life safed. I would say that if you figure the $1 billion cost per 30,- 000 workers, that is $30,000 per worker. That would mean that if we are being consistent with NHTSA, we would have to save one out of every eight workers. I don’t think that anybody would argue that one out of every eight workers who is presently above the one part per million standard is going to suffer from leu- kemia, much less die of it. Consumers Union, which is a consumer oriented pro- tection group, uses a figure of $1 million. Various other studies have cited numbers ranging from $150,000 to perhaps $3 million. I think it is critical that we recog- nize that trade off’s are being made here and that we have to at least have the information as to what types of benefits one part per million offers us. Let me get to my point about it not mattering what Arthur D. Little found. Let’s assume that all the costs of the Arthur D. Little study were multiplied by three. This becomes a $3 billion rather than a $1 billion ex- penditure. Would any de- [2109] cision, would any of the evidence presented today, vary in any way. Take another hypothetical. Let us assume that the previous witnesses had been able to quantify exactly how many lives would have been saved. Then they corrected their testimony and they said no, we are off by a factor of 10. Only one tenth as many people would be affected as we originally said. Is there anything that is part of this decision making procedure that would reflect that change in evidence? 44 I think that the answer is no. Unfortunately we haven’t acquired the evidence so that we could even test that particular hypothesis. I would like to make one further point about how one should treat costs here. All of the costs in the Arthur D. Little report and indeed in virtually all of the OSHA standards that I have read about, deal with average costs. They say how much will it cost us to move from ten parts per million to one part per million. They don’t ask the question about the benefits, but what we should like to know is not only how much does it cost us to move from 10 to one but how much does it cost us to move from 10 to two. We could always set the standard at two parts per million. We don’t have to deal with rounder numbers. Then we could see whether the further reduction to one part per million was worth- while. For example, if 20 cases of leukemia per year would be saved by this particular standard, then the cost of saving one [2110] life would be $50 million. Let’s as- sume, though, that we could save 19 of those cases for half of the expenditures by moving to two parts per million. Then that last life is costing us ten times as much. I think that the point that should be recognized is that when ADL or OSHA, when ADL conducts a study or when OSHA formulates and promulgates a standard, some attention should be marginal benefits and costs to further reductions seems absolutely essential. I would like to pose one disagreement I did have with OSHA in general and its treatment of economic costs which is that generally they only count when they get above a threshold. This is surprising for an agency that doesn’t accept thresholds going in the opposite direction to say that only if something is above five percent or only if an industry is closed down, in which case the real resources spent are, as Professor Henderson and Dr. Searbrough testified, are underestimated. Should we count this as economic costs that conceivably should af- fect our decision? So let me summarize very briefly what I say in my testimony. First, the proposed permanent standard: It 45 is not clear that any principal was used to set the stand- ard. One part per million is just as good as two parts per million or three parts per million. There is an avail- able technology methodology widely accepted in economics, widely accepted in the health care area, which is cost- effectiveness where we attempt to achieve [2111] maxi- mum benefits per dollar expenditure. Second, no attempt was made to determine marginal benefits. What will you gain if you tighten or lossen control? Third, no attempt was made to measure bene- fits. We get the same conclusion that I suggested ear- lier. Do we have much greater benefits or much lower benefits? Within the standard itself, there is little at- tempt to direct resources to where they would do the most good. It is noteworthy that this standard, one- third of the operating costs during the first year are directed to medical survailance, one third are directed to monitoring of conditions and one third are directed to reducing the risks. Well, do we have the appropriate information as to what gains we get out of either one of these different areas? If we did, then we could use even $1 million worth of resources to achieve substantially more health benefits both within the benzene related industries and in other industries. I guess what I would recommend for action is to un- derstand that we do not have the appropriate informa- tion that would enable OSHA to adopt, to reject, or to modify its standards. What is needed now are analyses to compute the total benefits from various levels of stand- ards and also information which was not provided on marginal benefits and costs. Unless we have this information, any decision taken by OSHA now must reflect an emotional or political re- sponse to an uncharted situation where the information isn’t available. [2112] I would hope that intelligent and well informed decision making should be giver a chance. Thank you. » * * _ [2141] MR. LE SOURD: Let me turn to Dr. Zeckhauser’s testimony if I may. Do I understand, Dr. Zeckhauser, that you are advocat- 46 ing the use of the techniques of the discipline called policy analysis and specifically that the application of cost ef- fectiveness analysis in the formulation of occupational health standards? I am correct? DR. ZECKHAUSER: I would say it is more than policy analysis. It is basically the way most effective government decisions are made and are sometimes put under that head. It is part of economics. It is part of government decision making. MR. LE SOURD: You are recommending cost effec- tiveness? DR. ZECKHAUSER: Yes, I am. MR. LE SOURD: Yes. Further, are you recommend- ing that no action be taken to promulgate such a stan- dard as this proposal? DR. ZECKHAUSER: I wouldn’t make that recom- mendation. The reason being all that I have learned from reading the Arthur D. Little report and I have not reviewed the medical evidence. I have heard a little bit of it. I have discussed it with people at API and with their legal counsel. All we know is the cost of [2142] this information, It is $1 billion. We know nothing about the benefits of this information. That strikes me as mak- ing a decision in ignorance. I think we should get some notion of what the effectiveness will be before we decide to make a decision of this sort. So my answer would be yes. We have no basis to make any possible decision. However, there are some improvements we could make even if we had to make a decision. I tried to be cost ef- fective within the standard. Looked to see which expen- ditures seemed most wasteful. But I would prefer to get the basic information as to what level of protection, if any, would be afforded. MR. LE SOURD: Is cost effectiveness always of the dr tn principal for use in regulatory action of this sort? DR. ZECKHAUSER: In protective regulation, it is frequently very useful. There are some times where a government regulatory agency may feel that it can put a price on a level of protection that is afforded. Otherwise it might chose to value a life. 47 I generally don’t think that that is very helpful. OSHA has objected violently to it and has therefore stopped its analysis more or less burrying its head in the sand. Cost effectiveness analysis just gives you a way of utilizing information to see, for example, that here maybe we are saving a life at a cost of $50 million where as we are failing to save lives, for example with the CAT scanner that I [2143] mentioned earlier, that would cost $500,000. We put more of our resources into CAT scan- ners which has been identified as a rather wasteful! technology by the government and less into protecting workers in this way possibly offering very minimal bene- fit, then we would be using cost effective analysis to do that determination. The basic principal is that it high- lights the trade off’s and allows decision makers at all levels. As you know, the President of the United States has expressed an interest in OSHA’s decision making processes to learn what is being gained at what cost. This is precisely the information, for example, that the workers in the refineries themeselves and the other establishments would use if they owned the refinery and had to make the decision, should we protect ourselves? My guess that if they did attempt to make that decision, they might decide that it was worthwhile living with a little more protective equipment. As you know, that is a very cost effective way of protecting people, but as you know that is also ruled out by traditional OSHA pro- cedures. I think that quantifying the effectiveness and the costs of various types of impositions would immediately inform decision makers within OSHA, within the govern- ment and within the nation as a whole as to what is be- ing gained at what cost and would enable OSHA to ration- alize its interventions getting more occupational safety and health for whatever level of re- [2144] sources that are spent. [2149] MR. LESOURD: Dr. Zeckhauser, you have said that the guiding principle of cost effective analysis is that for whatever level of resource expenditure we are undertaking we should attempt the maximum possible 48 level of effectiveness. Is this a correct definition, then, of cost effectiveness analysis? DR. ZECKHAUSER: That is part of it. The other part of it is that ultimately the decision maker should look at cost and effectiveness and decide what level of resources we want to spend. But, yes, that is an import- ant component, and we want to get maximum effective- ness for whatever level of resources we expend. MR. LESOURD: Would you agree that it is OSHA’s obligation to provide insofar as can be accomplished a safe and healthful workplace for workers? DR. ZECKHAUSER: As I remember the original enabling legislation, it was insofar as possible. Also, in the original legislation there was the term feasible, which has generally been interpreted to include technologically feasible. I think that any decision maker concerned for the total resources of cur nation—and this is the lesson of economics that you shouldn’t forget anything when you make your decision— [2150] would want to interpret that as being economically feasible as well. We shouldn’t buy miniscule protection for an extra-ordinarily high amount. The problem with saying safe and healthful is how safe is safe? At what level? Why one part per mil- lion? Why not .001 parts per million Why not zero parts per million and put the petroleum industry maybe out of business if we got an absolute zero because there is no way you can assure nothing will creep through any mode of protection? So the problem with saying safe and healthful by it- self, without qualification, is that there is no level that is safe and healthful. OSHA has run into this problem with regard to a number of its standards in that they haven’t been able to define that level. We had a stand- ard of ten parts per million. If that was safe and health- ful, then it is still safe and healthful. It is not as though the biology has changed at all. That was a decision we chose to make at that time on the basis of not very good information. We now it seems do not have much more good information, and we are just changing our standard. dout being killed in a hurricane. Now this might be true in the United States, but it may not be true in another country where hurricanes are an annual hazard. So isn’t it a question of selection of priorities? DR. WILSON: Oh, absolutely. Risk is certainly right to question. Of course, there are numbers on hurricanes in the United States which is also very important to note that although a hurricane is widely defined to be an act of God and of course in that sense it is. Nonetheless you can protect against it and reduce your risk, and a [2735] cautious person would look, in fact it is quite notable the people who calculate risks in this business of calculating risks, calculating them will in fact start avoiding hurri- canes and choosing their airlines rather carefully and so on. MS. KALARIS: Would you agree, then, if one’s prime objective is to protect as many workers as possible, one may not be willing to accept a risk which entails a few workers being exposed to a hazard? DR. WILSON: I am sorry, I don’t understand the question. MS. KALARIS: We said that, if I understood you correctly, you agreed that risks are relative. DR. WILSON: Correct. MS. KALARIS: Ok. If one’s primary objective is to protect as many workers as possible from a particular risk, one may not be willing to accept the risk which entails few workers being exposed to the hazard. In that case doesn’t the risk become a significant risk rather than an insignificant one? DR. WILSON: I am still not quite sure to understand it but let me try to answer and see if I have got it correctly. There is a prime objective for protecting human life, that is correct. In the framework of this hearing, [2736] re 87 one can talk about that limit that particular groups of people who are working people. Now indeed risk is a variable question and as I said, it is somewhat an in- dividual question. It is important not only to make sure that the risk to all of society be small, but there is no individual group in society which is unfairly being called upon to shoulder a very large section of the risks. I believe that that is perhaps what you were trying at in that question. I would agree with that that you should not ask one limited section of people to take unusually large risks merely for the benefit of the rest of society without some concomitant benefit for these people or giving them perhaps the opportunity of rejecting that particular option of accepting that risk. I will give an example. We all know that being an astronaut is a very risky business. Quite apart from the risk of the thing failing and exposed to cosmic rays and radiation at a level far exceeding the ordinary industrial level. Approximately one trip to the moon is 20 times the yearly dose for an occupational worker. The astronaut is asked to shoulder that risk. They shoulder it willingly; they would have an opportunity declining. Although they are exposed to a larger share of risk than anyone of the general population, I don’t think it is unreasonable. MS. KALARIS: On Tables III & IV, would you turn to [2737] those please? You state that on the basis of these tables, occupational exposure to benzene presents an insignificant risk. Are the risks calculated for these tables all hypothetical risks? DR. WILSON: No, they are not. Some of them are real. Some of them are known. Let’s see. MS. KALARIS: What — DR. WILSON: —Some of them are rather certain, and the ones on benzene are hypothetical and may be overstated. MS. KALARIS: Ok. What did you hypothesize? Or what assumptions did you make in calculating the risk of benzene? DR. WILSON: Oh, I went back. That is back on several pages back. That is a fairly normal, if I may go through the assumptions I made. 88 Starting with Figure 4, my Figure 4, I tried to make sense out of this highly discorded set of data. As I plot the data, I put various dotted lines on it. I have tried to assume that no one was completely wrong; that no one was actually lying or anything like this, but there was some misinterpretations of some parts of the data. Mr. Aksoy, for example, he found twice the standard cancer in Turkey, 13 parts per thousand. It is possible he missed quite a few cases so one can, I didn’t put it on the figure, but one [2738] might assume as Pat Faulker that twice as many cases is the dose level I thought was 200 parts per million. I believe he stated that. Faulker could clearly have missed some cases and one could go upwards on that. I was not quite sure what to make of recent NIOSH study. I had assumed as had Dr. Tabershaw gave testi- mony yesterday, that he was talking about these cases being 15 parts per million. I am not quite sure that he still holds to that, but we looked at it last night. It doesn’t explicitly say. Anyway, I was guessing that he had understated it, and that was more like to be 100 parts per million or even some different chemical. Because otherwise it is very hard to make sense of that data and at the same time assume that there aren’t too many shoemakers left in Turkey. Vigliani’s data, I assume, was slightly high. So I took the bottom curve on this, bottom line, the risk liner 1.8 times 10° per year at one part per million dosage. That is the slope of that line. That probably what the data really is assuming a straight line instance. That is saying a straight line is pessimistic. I could have taken one of the other lines with this discordant set of data, but I was reluctant to admit that everyone in Turkey was going barefoot. Then I said I have seven other cancer case in tobacco smoking, for [2739] example, we all know that the first case we found was lung cancer. Yet that there are lots bladder cancers we now come across, perhaps twice as many cancers as the number in the final cite. So I doubled that risk and brought it up to 3.5 times 10° at one part per million. Now, this would be risk—Oh, this risk by the way is 89 slightly overestimated risk, because that is by taking the ratio to the normal instance. Now if you look at, now the one reason for taking the ratio to a normal instance is to save myself work, and to use the work that other people have done. Because when you want to calculate the normal instance, you have got to complicate age correction on what the age of the people concerned with. I didn’t want to go through that work, but the people who have done these studies have done that work. By taking that ratio, you can factorize that part out. Now, this risk then becomes correct if people were ex- posed to this benzene not only their working life but until they die. But in fact, they are not exposed to the benzene for age 65 to age 80, and it is quite likely therefore the risk is overstated by a fact of two. Nonetheless, I have left that stand. So that number, 3.5 times 10°° per year at one part per million becomes 3.5 times 10-° per year at 10 parts per million. That is I calculated that risk. [2740] DR. WILSON: I don’t know that benzene might be a direct carcinogen. If it is a co-carcinogen only, then it is wildly overstated. MS. KALARIS: Doctor, what is the risk at 10 ppm as compared with the risk at one ppm? DR. WILSON: According to this way of calculating, it will be 10 times as much. Incidentally, that is one of the advantages of taking a linear calculation. Everytime people plan to do risk calculations and do these general calculations; Dr. Pochin, myself, other people; we always try and assume over a wide range there is a straight line curve. If you don’t do this, the calculations become tricky. It becomes much harder to visualize them, and so on, and so although this is perhaps overstating the benzene figure, I believe if you want to do public policy on a risk ealeu- lation basis, this is a fairly prudent and slightly conserva- tive thing to do. MS. KALARIS: Thank you. On page 28 of this state- ment, you assume that 30,000 people are now exposed to three ppm benzene concentrations. DR. WILSON: Yes, that was— MS. KALARIS: Can you explain the basis? 90 DR. WILSON: Yes. MS. KALARIS: For the level assumption? [2741] DR. WILSON: Yes, I was taking this report, the report of Arthur D. Little for OSHA. Now, the page number I have got here, Page six, second paragraph, was from the preliminary draft of this, and I must apologize. I only got the final thing a couple of days ago, and I should have updated that page reference. But they say in there somewhere, and it was page SIX, second paragraph, that the standard would effect 150,000 people, and only 30,000 of these now have concentrations above one part per million. I tried to get out of that study a number, a sort of graph of who is exposed to what. Maybe it is in there, but I didn’t find it. It is not very clear. It seems to me perhaps a weakness, it is not clear. I shouldn’t be grumbling about a report not being clear because many of mine aren’t either, but I couldn’t find that so I made the estimate; there is clearly going to be some distribu- tion. They won’t all be at the top. So I made a very rough guess that they were three parts per million. I believe that if you are to do this job properly, you are supposed to improve my risk estimate and go over this rather carefully and probably do a complete integra- tion over these numbers, but I am trying here to pull in what is, I believe, a major gap in the justification [2742] OSHA had for what they are doing, what they are pro- posing, and outline the method by which OSHA would do it. MS. KALARIS: On page 29, I believe you stated that only a few 100 people would be regularly exposed to 10 ppm of benzene concentration. Can you explain the basis of that statement? DR. WILSON: That is maybe incorrect. It came out of a page in this report here, and again, they were vague on this particular question. Therefore, I am a little vague on it. Probably, as I was thinking about it last night, I think a few hundreds; it is probably closer to 1,000 than 100, but I really don’t know. * * * * eT ee Srse 91 [2753] DR. LLOYD: Dr. Wilson, on page four, the paragraph on the [2754] page, you say, “I wish to make it clear that, of course, we did testify. I satisfied myself that benefits should be included. The manufacturing of benzene at ten parts per million level up-graded the potential risks associated therewith.” I would ask, bene- fits to whom and risks to whom? DR. WILSON: Okay. I possibly answer that ques- tion, of course, just now. There is a point here which your question brings out, that in fact, the potential risk will be to the benzene worker. It is going to be in my view a considerable benefit to society. There is an im- portant feature in any one of these cases, as in fact in all cases where anyone that is employed in any sort of occupation riding a bus or an aeroplane that some meas- ure of this benefit be passed upon individual workers, and there are various ways of doing it in society. A classic way in a really dangerous occupation, which this isn’t, is giving a worker hazard pay, but this is no way near that. But this has to be born in mind. DR. LLOYD: And then you do that since in com- parison to other risks which society regards as insig- nificant. Would you say that that little worker is insig- nificant? DR. WILSON: Pardon? DR. LLOYD: Would you say that the death of a [2755] worker is insignificant? DR. WILSON: The said the risks can be insignificant. I have never regarded death as insignificant. I can re- gard a risk as insignificant, but not a death. DR. LLOYD: Well, then, what are you referring to when you say, “Society regards them as insignificant.” What do you mean by “insignificant”? DR. WILSON: “Insignificant” in this case is much less than other—“Insignificant” would be in this regard a risk which in most people’s ordinary caiculation of what to do from one day to the next, you would not take account of even if you were aware of the details of the calculation. DR. LLOYD: Is that what we are talking about here ee “4p are talking about workers who died from leu- emia 92 DR. WILSON: Iam sorry. That is what I was talk- ing about on page five. Indeed, that is why I think the main important feature is my table, Table Three and Table Four. I think. Table Three is particularly im- portant. It is particularly important, it seems to me, to make sure that society is not asking a worker in a benzene factory to shoulder a risk which is appreciably greater than risk in any other occupation. That is the reason why I listed some of these. * * - * [2772] DR. LLOYD: When you said you estimated the risk of the benzene-leukemia problem, you described it as inspired guesswork. DR. WILSON: No. I think it is—in one direction it is a guess. In the following sense: I have, we have some data. It is a lousy set of data as we have had several times during this hearing. It is data on the interpretation of which people have disagreed, and now I have made a estimate, I think it is slightly better than a guess, on what the risk might be. Now you might—it is open to other people to disagree, but the reason why I think that it is more than a guess is, for example, suppose I was to assume that the latest NIOSH study of Infante and Young and people was literally correct and was five times the normal instance at ten parts per million of benzene. [2773] And I was also to assume that there was a plot which was approximately linear and no worse than linear between effect and dose. I see no reason why it should turn over. Then it would be very hard to say why at two hundred parts per million you would not just be getting five times the normal instance, you would of course have to be getting one hundred times the normal instance. As I said before, I just don’t see how there can be a shoemaker in Turkey left. And although I know, no doubt, there are some people in Turkey that go without shoes, I don’t think everybody does. And therefore, I don’t believe that it is merely guess- work. It is correlated. Trying to correlate this piece of information, trying to explain—that is why somewhere in here I may have said it is very hard to take that study aii na. 93 completely literally. Of course, I must say that I made an error in my reading. I don’t think they said that those cases were ten parts per million. There may have been some sort of implication there, that I thought there was. If there are higher figures, or in fact due to other chemi- cals, then that could be the explanation of that figures. It is hard to say that it turned out not to be benzene at that dose level. It might be, but that would be very much upsetting all the indications that we have got. * * * * [2820] MR. MACDONALD: Your Honor, we do know that Dr. Aksoy has done extensive industry research. DR. WILSON: I knew that and I forgot that. DR. LLOYD: You have made reference a number of times to Dr. Aksoy and to shoemakers. In reference to your statement that all of the shoemakers in Turkey should be dead on the basis of the Infante estimate— DR. WILSON: Yes. No. Not on the Infante esti- mates but upon the estimates of the Iufante Study if they were at 10 parts per million. DR. LLOYD: I realize what you are saying. Now, couldn’t it be that with benzene we might have a situa- tion analogous to what we have in beryllium and with asbestos where the people who are at the very high ex- posures show an acute disease which is not presented as cancer as is presented in beryllium and asbestos and it turns out in the end result when we look at these patients that the people who have the long latent disease are people who got essentially lower exposures. Couldn’t that be the case with benzene? Particularly in light of Dr. Aksoy’s report with so many of the shoemakers dying from their blood dysecrasia. DR. WILSON: What you are suggesting to me is that there might be really different dose-response curves for this particular case? DR. LLOYD: Yes. [2821] DR. WILSON: It is conceivable, I suppose, that any dose—response curve is possible. I would— It would be a rather unusual, almost I think, revolutionary con- tribution to the literature on cancer to have a dose- response curve on cancer. 94 DR. LLOYD: You agree with what I am describing is true for beryllium and for asbestos? DR. WILSON: Well, beryllium is not a carcinogenic in this way. DR. LLOYD: It i: not a carcinogen? DR. WILSON: Not in this way. I mean it is not a direct carcinogen. I don’t know that it is direct. The people I know who had beryllium poisoning have not died from a carcinogen. It does not have the carcinogenic properties. They have mostly died of ankylinicosis which is not a carcinogen. DR. LLOYD: Are you going to be attending the beryllium hearings? DR. WILSON: No. DR. LLOYD: I would suggest you do. DR. WILSON: I haven’t time to attend all hearings and still try and understand what is going on in one or two of them. DR. LLOYD: Now in reference to insignificant [2822] risk when talking about risk as a personal guess in compared to other things and how you do this yourself relative to matters like jumping off— DR. WILSON: That is right. DR. LLOYD: Do you know whether in general work- ers exposed to benzene, or for that matter, any person, were ever given a chance to make such a conscious choice? DR. WILSON: Yes. Some workers are. I don’t know if all workers are. A person is given—certainly in the radiation field which I know a little more than in the carcinogenicist’s field. A person who is employed is told that he is a radiation worker and told to carry a film badge and can deem to accept this job or you can accept it if you wish. And you can take another job, maybe in the same company. 95 [Exhibit 2-46 (list of references omitted in printing) | OSHA TRANSLATION OSHA-76-62 Med Lavoro 46:194-198, 1955 STUDY OF THE PERCUTANEOUS BENZENE ABSORPTION By G. L. Conea and A. Maltagliati “L. Devoto” Labor Clinic, Milan University Director: Prof. Enrico C. Vigliani We believe that a study of percuteaneous benzene ab- sorption is timely; accordingly, we performed a series of experiments in man, involving direct contact with liquid benzene, i.e., the tests were implemented under conditions which actually reproduce those forms of contact which occur during industrial use. For a prolonged period of time—we may safely say ever since the professional study of benzene pathology started—various authors investigated the possible pene- tration of the toxin through the cutis surface. The characteristics of the substance which is a power- ful lipid solvent, soon led to the assumption that benzene with its significant lipolytic properties active at skin level. could break through the protective cutaneous barrier; it was suspected that the substance enters the circulation over that path and disperses in the organism. Santesson was first to investigate the problem experi- mentally in 1897. His tests were performed in rabbits with the application of pure benzene pads on the shaved cutis. He reached the conclusion that benzene absorption does occur. Translated for US Department of Labor, OSHA from Italian by LEO KANNER ASSOCIATES, P.O. Box 5187, Redwood City, Cali- fornia 94063, (415) 365-3046, October, 1975. 96 [2] Later Mauro, Lazarew, Brussilowskaja, Lawrow and Lifshitz, expressed analogous opinions, always on the basis of animal experiments. Mauro used guinea pigs, placing pure benzene packs on their cutis and leaving these in place for two hours every second day. Introducing an alternative of the Santesson method, depilation was used instead of shaving the guinea pigs so as to avoid abrasions through which benzene might penetrate. LORE Lazarew, Brussilowskaja, Lawrow and Lifshitz experi- mented with rabbits, soaking a paw in a pure benzene bath and attempting to prevent the animals from inhaling vapors originating from the bath. In a monographie study on solvent pathology, Lehmann and Flury contested the conclusions reached by the above authors. They found instead that no cutaneous absorption could take place, nor would the absorption be of any interest in practice; they limited the question to an ex- clusively theoretical level. Petrilla conducted interesting research work in labora- tory animals. He tested 15 guinea pigs, in part with intact fur, in part after mechanical or chemical depila- tion. The animals were subjected to benzene evaporation involving the cutis of the entire body, excepting the head. The presence of intoxication symptoms was verified in almost all animals, including some guinea pigs with intact fur. The last-mentioned animals showed, after 6 days of testing, cutaneous modifications as well as macroscopic changes such as hyperemia, edemas and chapped skin lesions. The author interpreted the results by confirming the possible capacity of benzene to transgress the cuta- neous barrier, even when said barrier is intact. More recently, Nunziante Cesaro showed interest in the problem. This [3] author refers to experiments per- formed in man. Individuals with perfectly sound cutis were placed for a period of 20 to 30 minutes into a metal tank in which the atmosphere was saturated with ben- zene. The head of the test subject was kept outside through an opening in the tank; a rubber tube linked to a face mask provided inhalation of vapor-free air. The dosage of the urinary sulfate derivatives was determined 97 before, immediately after, one hour after and two hours after the start of the experiment. The practically unchanged SI/ST ratio and the absence of benzene in the air led the author to the conclusion that percutaneous absorption does not take place, at least not when the cutis is perfectly intact. Subsequent investigations resulted negative as well; they involved the application of cotton wool layers satu- rated with benzene on the upper limb cutis of some test subjects. The limb was kept for 20 to 30 minutes in a sealable sleeve. No benzene was recovered, not even in traces, from the exhaled air of this second test subject group. Based on the total opinions stated in literature, the conclusion can be reached that two diametrically opposite views exist, both supported by a considerable number of authoritative researchers. However, early experiments performed in animals are readily subject to criticism because the applied techniques either fail to guarantee the perfect integrity of cutaneous surfaces in contact with benzene, or do not strictly exclude possible inhalation of the toxin. On the other hand, under close scrutiny even research in man does not prove to be entirely convincing. In our opinion, the principal objection against the work of these authors concerns the use of air saturated with benzene and the use of pads saturated with the solvent; these contact methods can be defined as “indirect”. [4} Said methodology can be justified by the attempt made to preserve the test subject from any morbid symp- toms, including their cutaneous forms; the method never- theless results in a questionable solution of the problem since (said method) is incomplete. We do not believe—even from a purely theoretical viewpoint—that it is actually suitable to investigate possible percutaneous absorption of a liquid such as ben- zene in contact with the skin of a worker by using vapors in saturated form or by extending the contact over the entire body surface; physiologic knowledge concerning cutaneous permeability does a priori exclude any absorp- tion in that form in case of lipo-solvents as well. 98 bove objection essentially also applies to the use of perio wool tae with benzene, placed on the cutis of a limb in a sealed sleeve. Under such conditions a transient and incomplete contact with the liquid ehh will evidently occur; but, since benzene evaporates rapi y; it will never be present in a volume sufficient for vee absorption, and the result will merely be a vapor-saturate ere in the sleeve. “S) an above-mentioned reasons our research work pased on different criteria. We alectaa test subjects, including a female, to evaluate the effect of individual cutaneous characteristics. The tests were performed on alternate days. Direct contact with the toxin was accomplished by im- mersion in “commercial” benzene of the type used by a large factory manufacturing rubber articles. Maximal contact duration was limited to 25-35 minutes because already after a contact duration of 5 to 10 minutes from the start of testing the exposed cutis surface became in- tensely and increasingly painful; the [5] pain was char- acterized by a burning sensation. The following technique was applied (see the photo- graphic description of the instruments) : The subject introduces a hand and 2/3 of the forearm into a metal tank supported by a tripod; the surface of the tank has an opening fitted with a rubber sleeve and can be completely sealed; a face mask with double valve is then applied to the subject who starts to inhale, through a long rubber tube, air from the external environment. This protects against vapor inhalation during the test. Benzene is introduced in to the tank through a tube at- tached to a suitable container. Towards the end of the testing period a hog bladder with an approximate capacity of 3 liters is attached to the exhalation valve of the mask; it becomes thus possible to collect an air sample and verify whether it contains any benzene vapors. [Figure 1 omitted in printing] We used two methods to determine the eventual per- cutaneous penetration [6] of benzene. With these meth- 99 ods, the elimination of the toxin from the organism can be controlled, i.e., the dosage of urinary sulfa derivatives can be determined and the presence of benzene in the exhaled air can be investigated. We applied the Folin gravimetric method to determine the urinary sulfa derivatives. We took urine specimens before and two hours after terminating the experiment when—according to various authors—the elimination of sulfa derivatives, caused by the absorption of benzene, is maximal. For benzene verification in exhaled air we used the following procedure: the air exhaled by the test subject during the final minutes of the experiment is collected in a hog bladder, it is subjected to effervescence (bub- bling) with the use of a suitable pump (Orsat apparatus) in a solution constituted by 10 ce of H.SO, and 1 ce of 40% formaldehyde. The presence of benzene in the bubbling air causes brownish-red discoloration of the solution, which is colorimetrically compared with a solu- tion sample containing 1% nitroprussiate of sodium. With the aid of a suitable scale, benzene concentration in the exhaled air is determined from the number of pump- ing strokes (pompate) needed to obtain a coloration simi- lar to the color of the control sample. The obtained results are shown in the Table, see next page. On the basis of these results we exclude the possible percutaneous penetration of benzene under the testing conditions adopted by us, i.e., with intact cutis, by means of contact between liquid benzene and a limb surface including the hand and two thirds of the forearm, during 25 to 35 minutes. The above statement is confirmed by the collected data, primarily by the constant absence of benzene, even in [Table I omitted in printing] minimal traces, from the air exhaled [7] by the subject at the termination of the experiment; secondly, the above is confirmed by variations of urinary sulfa derivative excretion which do not exceed physiologic fluctuations con- i all 100 sidered normal (Vigliani and Gemelli: maximal daily variation = + 7; hour by hour variations = + 2). Moreover, we feund that none of the tested subjects complained during or after the experiments about dis- orders of a general or local type which could be inter- preted as benzene intoxication symptoms; nor were al- terations or lesions of any kind found on cutis surfaces exposed to contact with the toxin. We therefore share the opinion of researchers who con- tend that the penetration of benzene into the organism through the skin is impossible and [8] that the problem is not significant for practice. The penetration did in fact prove to be non-existent, even when testing methods were applied which involved direct contact maintained to the limit of the test subject’s sensitivity, according to systems which do not only reproduce, but even emphasize systems used in industrial practice. SUMMARY An experiment was carried out to study the possibility of benzene being absorbed through the skin. Three sound men were subjected to the immersion of their hands and forearms in commercial benzene for 25-35 minutes. Urine sulfates were then determinated and researches made for benzene in the expired air. No benzene was found in the air expired by the subjects at the end of the experiment; no modification was noted in the inorganic-total urine sulfates ratio. The possibility of a percutaneous passage of benzene in the experimental conditions adopted is therefore rejected. 101 [Exhibit 2-47 (listing references omitted in printing) ] OSHA TRANSLATION OSHA-76-60 Med Lavoro 37:151-56, 1946 IS PERCUTANEOUS BENZENE ABSORPTION POSSIBLE? By Dr. Angelo Nunziante Cesaro, volunteer assistant “Luigi Devoto” Labor Clinic, Milan University (Director: Prof. Enrico C. Vigliani) Percutaneous penetration is mentioned among the pene- tration modes of benzene into the human organism. We refer to Santesson (1897) (Ref. 1), who was one of the first researchers to state that such a possibility definitely exists. His experimental research was carried out in rabbits to the cutis of which pure benzene packs were applied after removal of the fur; the packs were kept in place with bandages. Subsequently (1925) Mauro (Ref. 2), obtained a similar result when testing chemically depilated guinea pigs: packs of pure benzene were applied for 2 hours each for two days. Said author, while never able to verify death among these animals, observed modi- fications of the morphologic-hematic aspect, a definite indication of starting intoxication. Lazarew, Brussilowskaja, Lawrow and Lifschitz (Ref. 3) kept the paw of a rabbit immersed in a benzene bath, while preventing the animal from inhaling vapors origi- nating from the bath; they likewise determined the pres- ence of benzene in the exhaled air and therefore reached the conclusion that percutaneous absorption of the solvent is possible. Translated for US Department of Labor, OSHA from the Italian by LEO KANNER ASSOCIATES, P.O. Box 5187, Redwood City, Cali- fornia 94063, (415) 365-3046, October, 1975. 102 At variance from the above, K. B. Lehmann and F. Flury (Ref. 4), in [2] their monograph on solvent path- ology, state that the penetration of benzene through the cutis should be considered from a theoretical standpoint only, since they were never able to determine the per- cutaneous absorption of the toxin chemically. Recently, the problem was re-examined by Petrilli (Ref. 5). This author experimented with five groups of guinea pigs. Each group included three guinea pigs weighing 450 to 600 g each. The five groups differed as follows: No. 1 guinea pigs with intact fur; No., 2 fur sheared off with scissors; No. 3 depilated with a razor; No. 4 depilated with chemical agents; No: 5 control ani- mals. Benzene was applied to them by means of vaporiza- tion while the animals were sealed in appropriate devices; their heads were kept outside of the environment con- taining the vaporized solvent. The overall result of the investigation revealed that the animals of Groups No. 1— of primary interest here because they were intact— showed slight intoxication symptoms on the 4th day; but only two of the three animals were affected. The author states that the animals showed cutaneous changes on the 6th day, evident to the unaided eye, such as hyperemia, edema, scaly skin lesions; he believes that benzene is able to break through the cutaneous barrier, even in some cases when said barrier is intact. A critical evaluation of the research work carried out by the cited authors prompts us to divide their work into two groups; the first includes Santesson and Mauro’s studies and the second those of Lazarew, Brussilowskaja, Lawrow and Lifschitz and Petrilli. The investigations of Santesson and Mauro are of con- siderable interest insofar as these authors were among the first to provide some data on slow benzene intoxica- tion. But the possibility cannot be entirely excluded that [3] the animals on whom the benzene packs were applied might have inhaled the toxin. Therefore the work of these authors cannot be taken into consideration for the pur- poses of present study. On the other hand, said authors mainly intended to investigate the first symptoms of slow benzene intoxication. 103 The research work of Lazarew, Brussilowskaja, Lawrow and Lifschitz and of Petrilli are subject to criticism inso- far as it cannot be ascertained whether the cutis of the animals treated by them were entirely intact. In fact, Petrilli found macroscopic cutaneous lesions already on the 6th day of treatment, while the first slight intoxi- cation symptoms appeared only two days earlier. The possibility can therefore not be entirely excluded that cutaneous lesions caused by fur shaving or by the pro- longed effect of benzene on the cutis—while roughly de- terminable only—could already have been active during the days preceding the appearance of the initial symp- toms. * * * * Since the actual status of the problem had reached this point, we believed that a study of the question would by useful, also in view of the authoritative statements made by Lehmann and Flury. We used men free from skin lesions as test subjects. A few days before the experiment, we prescribed a diet » ‘ch in carbohydrates (bread, potatoes, etc.) and green vege- tables. The diet contained very little protein, so as to reduce matter causing intestinal putrefaction to a mini- mum. Each test subject was placed nude into a metal tank for 20’ to 30’. The tank had a capacity of 8,317 me and was perfectly airtight. The head of the subject remained out- side, for which purpose the tank lid had an aperture; rubber sleeves prevented the escape of air from the inside of the tank to its exterior, and sealed the aperture through which the subject’s neck was [4] passed. Moreover, after closing the subject’s nostrils with a clasp, a mask was applied. The subject breathed through the mouth, using the 5 meter-long rubber tube fitted to the mask, and in- haled air originating from a courtyard beyond the cham- ber where the tank was located; the tube passed through a window. A benzene-saturated atmosphere was obtained in the tank by introducing several cotten wool pads soaked with the solvent. Furthermore, the subject applied liquid benzene to his skin within the tank, using cotton wood pads, also saturated with the solvent (see Fig. 1). [Figure 1 omitted in printing] 104 Urine eliminated before the subject was placed into the tank, eliminated immediately after placement in the tank, one hour and two hours later was used for the determi- nation of total inorganic sulfates with the aid of the Folin gravimetric method. [5] We wish to premise, so as to justify the research work and sulfate dosage as well as the ratio between in- organic sulfates: total sulfates, that the research work of Yant, Schrenk, Sayers, Horwarth and Renharth (Ref. 6), Yant, Schrenk and Patty (Ref. 7), Gueffroy and Luce (Ref. 8), Vigliani and Giannini (Ref. 9), Girino (Ref. 10), Vigliani and Gemelli (Ref. 11) showed a rapid and significant decrease in the ratio between inorganic sul- fates and total sulfates. As a consequence of benzene absorption, the first diminish while the second increase. The modifications reach their maximum two hours after the termination of the test subject’s exposure to benzene vapors. Urine sulfate dosage determination is carried out with the Folin method, which we will briefly describe here. INORGANIC SULFATES.—25 ce urine is filled into an Erlenmeyer of 200 to 250 cc; then 100 cc H.O and 10 ce HCl, diluted in H.O with a volumetric ratio of 1:4 is added. 10 cc of an aqueous 5% BaCl, solution is added drop by drop during continuous agitation with a glass rod. The mixture is left standing for one hour; filtration of the same follows through a Schleicher-Schull filter (blue band) ; the filtration is carefully accelerated, using a vacuum bottle connected with a water pump. The filter is burned in a porcelain crucible which had been ac- curately weighed; the crucible is kept at a temperature of 700 to 800° for a couple of hours. Cooling follows in the desiccator and a final exact weighing is performed. The weight difference in mg is the (weight of) in- organic sulfates contained in 25 ce of urine. TOTAL SULFATES.—25 ce urine and 20 ec HCl, diluted as specified above, are filled into an Erlenmeyer of 200 ce capacity. Boiling for at least 20’ follows, while the Erlenmeyer’s outlet is covered with a crucibie slide {6] (vetrino da crogiolo) which has the overall function 105 of cooling, heating and regulating the boiling process, moderating the same to prevent the desiccation of the container. The container is then cooled under running water for 2’-3’; 50 ce of H.O is added; then 60 ce of 5% BaCl, is added drop by drop during continuous agitation with a glass rod. The next steps are similar to the procecure followed in case of inorganic sulfates. [Table omitted in printing] [7] Our investigations show that the ratio inorganic sulfates, total sulfates was not significantly modified as a consequence of cutis exposure to benzene vapors and simultaneous cutaneous application of the liquid solvent. The observed slight variations are within the limits of fluctuations found in normal subjects, since the S.I. : S.T. ratio is near-constant at various hours of the day; fluctu- ations generally do not exceed + 2%. (Vigliani and Gemelli). (1.c.). In addition to the examination of urine sulfates, we also investigated the benzene content of air exhaled by the same test subjects. For this purpose, the apparatus suggested by the British Home Office was used, previously tested in this Clinic by Vigliani and Reina (Ref. 12). The apparatus proved to be suitable for the determination of minor solvent volumes in the exhaled air as well, and it is suitable for the qualitative verification of traces. The apparatus consists of a mechanism to activate bubbling of the exhaled air through a solution of formalin in concentrated sulfuric acid. The presence of benzene causes brownish discoloration of the solution, which is more or less accentuated. The color is comparable to a test tube containing a 1% solution of sodium nitroprus- siate. Starting from the air volume needed for bubbling, so as to obtain a color equal to the sample color, the benzene concentration in the air is determinable with the aid of a suitable calibration table. The examination of benzene in air exhaled while the test subjects remained in the tank and while their cutis was exposed to benzene vapors and kept in contact with liquid benzene, always resulted negative. 106 Another investigation involved the application of ample cotton wool [8] layers soaked in pure benzene on the [Figure 2 omitted in printing] cutis of an upper limb of all test subjects. These re- mained on the limb which was kept in a cardboard tube, sealed at its end and perfectly airtight, fitted with rubber sleeves (see Fig. 2). During the final minutes of the test, for approximately 20’ to 30’, the possible presence of benzene was examined in the air, with the aid of the above-mentioned method. Not even traces of the solvent could ever be determined nor recovered in any of the performed experiments. In view of our experiments, we can therefore exclude a percutaneous absorption of benzene, at least to any ap- preciable extent, through intact cutis. SUMMARY An investigation was performed to determine whether benzene absorption through the intact cutis of man is possible. The cutis of the trunk and the limbs of 8 sound [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40385006_0035%3A05. Public record. Not legal advice.