Phosphine; Pesticide Tolerances

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 180, 185 and 186

[OPP-300865; FRL-6082-4]

RIN 2070-AB78

Phosphine; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: Tolerances are being revised and consolidated for residues of

phosphine in or on certain agricultural commodities and animal feeds.

None of these proposed tolerances are new, although this change would

facilitate new application methods. The Agency is merely changing the

tolerance expression to eliminate references

concerning how the phosphine gas is generated.

DATES: Comments, identified by the docket control number [OPP-300865],

must be received on or before July 9, 1999.

ADDRESSES: By mail, submit written comments to: Public Information and

Records Integrity Branch, Information Resources and Services Division

(7502C), Office of Pesticide Programs, Environmental Protection Agency,

401 M St., SW., Washington, DC 20460. In person, deliver comments to:

Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.

Comments and data may also be submitted electronically to: opp-

[email protected]. Follow the instructions under Unit VI. of this

document. No Confidential Business Information (CBI) should be

submitted through e-mail.

Information submitted as a comment concerning this document may be

claimed confidential by marking any part or all of that information as

CBI. Information so marked will not be disclosed except in accordance

with procedures set forth in 40 CFR part 2. A copy of the comment that

does not contain CBI must be submitted for inclusion in the public

record. Information not marked confidential will be included in the

public docket by EPA without prior notice. The public docket is

available for public inspection in Rm. 119 at the Virginia address

given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding

legal holidays

40 CFR part 2. A copy of the comment that

does not contain CBI must be submitted for inclusion in the public

record. Information not marked confidential will be included in the

public docket by EPA without prior notice. The public docket is

available for public inspection in Rm. 119 at the Virginia address

given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding

legal holidays.

Interested persons are invited to submit comments on the proposed

regulation. Comments must bear a notation indicating the docket control

number [OPP-300865].

FOR FURTHER INFORMATION CONTACT: By mail: Dennis McNeilly, Registration

Division [7505C], Office of Pesticide Programs, Environmental

Protection Agency, 401 M St., SW., Washington, DC 20460. Office

location, telephone number, and e-mail address: Crystal Mall #2, 1921

Jefferson Davis Hwy., Arlington, VA, (703) 308-6742, e-mail:

McN[email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of December 23,

1998, (FRL-6053-6), EPA announced the availability of the

Reregistration Eligibility Decision (RED) for aluminum and magnesium

phosphide, which was signed on September 30, 1998. This document

discusses in detail the Agency's risk assessment for these two very

similar pesticides.

Current tolerances established for aluminum and magnesium phosphide

are expressed in terms of residues of the fumigant phosphine resulting

from the use of aluminum and/or magnesium phosphide, respectively. Both

of these chemicals have very similar use patterns, chemical properties

and both result in the same residue (hydrogen phosphide), both

qualitatively and quantitatively. In fact, due to the high reactivity

and volatility of these two compounds the detection of finite residues

is not expected and the residue data indicate non- detectable levels of

phosphine, when label directions concerning aeration for 48 hours

before entering into commerce are followed

roperties

and both result in the same residue (hydrogen phosphide), both

qualitatively and quantitatively. In fact, due to the high reactivity

and volatility of these two compounds the detection of finite residues

is not expected and the residue data indicate non- detectable levels of

phosphine, when label directions concerning aeration for 48 hours

before entering into commerce are followed. The Agency has decided to

revise the current tolerance expressions because it does not matter

from a safety or practical standpoint, i.e. tolerance enforcement

purposes, whether residues of phosphine result from treatment with

aluminum phosphide or magnesium phosphide. In fact, having tolerances

expressed in this manner precludes treatment of the food and/or feed

commodities with phosphine gas delivered or generated via different

technology. Different application techniques involving direct

application of phosphine gas have the potential to reduce worker

exposure because fumigators would not need to enter the facility being

fumigated.

The aluminum and magnesium phosphide RED states that the tolerances

listed under 40 CFR 180.225 (a) and (b), 185.200, and 186.200 and

tolerances for magnesium phosphine listed under 40 CFR 180.375 (a) and

(b), 185.3800, and 186.3800 should be amended to consolidate all of

these tolerances in the Code of Federal Regulations. Following passage

of the Food Quality Protection Act (FQPA), tolerances for pesticide

residues in all types of food (raw or processed) are set under the same

provision of the law and EPA is including all such tolerances in part

180 of the Code of Federal Regulations. The Agency will list all

aluminum phosphide and magnesium phosphide tolerances under 40 CFR

180.225 and be subdivided into paragraphs (a)(1), (a)(2), (a)(3), and

ty Protection Act (FQPA), tolerances for pesticide

residues in all types of food (raw or processed) are set under the same

provision of the law and EPA is including all such tolerances in part

180 of the Code of Federal Regulations. The Agency will list all

aluminum phosphide and magnesium phosphide tolerances under 40 CFR

180.225 and be subdivided into paragraphs (a)(1), (a)(2), (a)(3), and

(a)(4). Tolerances in the new paragraph (a)(1) concern residues

resulting in or on Raw Agricultural Commodities (RACs) from post-

harvest fumigation uses. Tolerances in paragraph (a)(2) concern

residues in or on RACs from preharvest treatment of pest burrows in

agricultural and non-crop land areas. The Agency notes that this use

involves control of vector borne disease, especially in the

southwestern United States. Paragraph (a)(3) concerns residues

resulting from fumigation of processed foods. Finally, paragraph (a)(4)

concerns residues resulting from fumigation of animal feeds. There are

no tolerances established, nor are there any uses registered, for the

direct treatment of any field crop or greenhouse-grown food commodity.

The Agency recently updated the list of raw agricultural and

processed commodities and foodstuffs derived from crops (Table 1 OPPTS

GLN 860.1000). As a result of changes to this table, commodity

definitions used in the CFR also need to be updated. For example,

instead of a tolerance expressed as corn, it should now specify corn,

grain or corn, forage, etc. Further, since the tolerances for phosphide

will be combined under a single tolerance expression for phosphine,

several commodities with tolerances currently listed under both

aluminum and magnesium phosphide would need only one tolerance. The

Agency notes that it is impossible for a laboratory to determine from

strictly analytical methods whether phosphine residues resulted from Al

or Mg phosphide application and for risk assessment it is irrelevant

d under a single tolerance expression for phosphine,

several commodities with tolerances currently listed under both

aluminum and magnesium phosphide would need only one tolerance. The

Agency notes that it is impossible for a laboratory to determine from

strictly analytical methods whether phosphine residues resulted from Al

or Mg phosphide application and for risk assessment it is irrelevant.

In addition, with the required 48-hour aeration period required on all

labels, finite residues are not expected in/on any food commodity.

I. Risk Assessment and Statutory Findings

New section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a

tolerance (the legal limit for a pesticide chemical residue in or on a

food) only if EPA determines that the tolerance is ``safe.'' Section

408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable

certainty that no harm will result from aggregate exposure to the

pesticide chemical residue, including all anticipated dietary exposures

and all other exposures for which there is reliable information.'' This

includes exposure through drinking water and in residential settings,

but does not include occupational exposure. Section 408(b)(2)(C)

requires EPA to give special consideration to exposure of infants and

children to the pesticide chemical residue in establishing a tolerance

and to ``ensure that there is a reasonable certainty that no harm will

result to infants and children from aggregate exposure to the pesticide

chemical residue. . . .''

EPA performs a number of analyses to determine the risks from

aggregate exposure to pesticide residues. For further discussion of the

regulatory requirements of section 408 and a complete description of

the risk assessment process, see the Final Rule on Bifenthrin Pesticide

Tolerances (62

FR 62961, November 26, 1997)(FRL-5754-7).

II. Aggregate Risk Assessment and Determination of Safety

.''

EPA performs a number of analyses to determine the risks from

aggregate exposure to pesticide residues. For further discussion of the

regulatory requirements of section 408 and a complete description of

the risk assessment process, see the Final Rule on Bifenthrin Pesticide

Tolerances (62

FR 62961, November 26, 1997)(FRL-5754-7).

II. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D), EPA has reviewed the

available scientific data and other relevant information in support of

this action, EPA has sufficient data to assess the hazards of phosphine

and to make a determination on aggregate exposure, consistent with

section 408(b)(2), for residues of phosphine in or on almond, nutmeat

at 0.1 parts per million (ppm); avocadoes at 0.01 ppm; bananas at 0.01

ppm; barley, grain at 0.1 ppm; Brazil nut at 0.1 ppm; Cabbage,Chinese

at 0.01 ppm; cacao, bean at 0.1 ppm; cashews at 0.1 ppm; citrus, citron

at 0.01 ppm; coffee, bean, green at 0.1 ppm; corn, field, grain at 0.1

ppm; corn, pop, grain at 0.1 ppm; cotton, seed, undelinted at 0.1 ppm;

date, dried at 0.1 ppm; eggplants at 0.01 ppm; endive (escarole) at

0.01 ppm; filbert at 0.1 ppm; grapefruit at 0.01 ppm; kumquats at 0.01

ppm; Legume vegetables succulent or dried group(excluding soybeans) at

0.0 1 ppm; lemons at 0.01 ppm; lettuce at 0.01 ppm; limes at 0.01 ppm;

mangoes at 0.01 ppm; millet, grain at 0.1 ppm; mushrooms at 0.01 ppm;

oats, grain at 0.1 ppm; oranges at 0.01 ppm; papayas at 0.01 ppm;

peanut, nutmeat at 0.1 ppm; pecans at 0.1 ppm; peppers at 0.01 ppm;

persimmons at 0.0 1 ppm; pistachios at 0.1 ppm; rice, grain at 0.1 ppm;

rye at 0.1 ppm; safflower seed at 0.1 ppm; salsify tops at 0.01 ppm;

sesame seed at 0.1 ppm; sorghum grain at 0.1 ppm; soybeans at 0.1 ppm;

sunflower, seed at 0.1 ppm; sweet potatoes at 0.01 ppm; tangelos at

0.01 ppm; tangerines at 0.01 ppm; tomatoes at 0.01 ppm; walnuts at 0.1

ppm; wheat, grain at 0.1 ppm; all Raw Agricultural Commodities (RAC)

resulting from preharve

ice, grain at 0.1 ppm;

rye at 0.1 ppm; safflower seed at 0.1 ppm; salsify tops at 0.01 ppm;

sesame seed at 0.1 ppm; sorghum grain at 0.1 ppm; soybeans at 0.1 ppm;

sunflower, seed at 0.1 ppm; sweet potatoes at 0.01 ppm; tangelos at

0.01 ppm; tangerines at 0.01 ppm; tomatoes at 0.01 ppm; walnuts at 0.1

ppm; wheat, grain at 0.1 ppm; all Raw Agricultural Commodities (RAC)

resulting from preharvest treatment of pest burrows in agricultural and

non-cropland areas, 0.01 ppm; phosphine residues resulting from

fumigation of processed foods, 0.01 ppm; and phosphine residues

resulting from fumigation of animal feeds, 0.01 ppm.

EPA's assessment of the dietary exposures and risks associated with

establishing the tolerance follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered its

validity, completeness, and reliability as well as the relationship of

the results of the studies to human risk.

The Agency does not normally use inhalation studies for oral

(dietary) risk assessments. However, inhalation studies were used for

these chemicals because: (1) Use of an inhalation ``dose'' provides a

conservative approach for oral risk assessments; (2) these studies

enable the Agency to quantify the dosage of phosphine exposed to

laboratory animals; (3) the Agency required inhalation studies (rather

than oral studies) for this chemical because exposure to this chemical

via inhalation is much more likely for those individuals who would have

occupational exposure.

EPA has also considered available information concerning the

variability of the sensitivities of major identifiable subgroups of

consumers, including infants and children. The nature of the toxic

effects caused by phosphine are discussed below.

1. Acute toxicity. A rat acute inhalation study on phosphine

indicated an LC50 greater than 11 ppm, the highest dose

tested (HDT). This puts phosphine in Toxicity Category I, i.e., Highly

Toxic

concerning the

variability of the sensitivities of major identifiable subgroups of

consumers, including infants and children. The nature of the toxic

effects caused by phosphine are discussed below.

1. Acute toxicity. A rat acute inhalation study on phosphine

indicated an LC50 greater than 11 ppm, the highest dose

tested (HDT). This puts phosphine in Toxicity Category I, i.e., Highly

Toxic.

Given aluminum and magnesium phosphide's use patterns and chemical

characteristics, the other acute toxicity 81-series guideline studies

used to establish precautionary labeling were waived for these

chemicals as they would not change the Toxicity Category or effect

protective clothing requirements. The material of concern is phosphine

gas which is the material with pesticidal properties, when either

aluminum or magnesium phosphide are used.

2. Subchronic toxicity. In a 90 day rat inhalation study, Fischer

344 rats (10/sex/dose) were exposed to phosphine 6 hours/day, 5 days/

week for 13 weeks at levels of 0, 0.3, 1.0 or 3.0 ppm. Additional

groups (3-5/sex/group) were exposed at 0 or 10 ppm starting at week 8,

and 0 or 5 ppm starting at week 12. Recovery groups were included in

the study at each dose level and sacrificed after 4 weeks of post-

exposure observations. In the groups exposed at levels up to 3.0 ppm,

there was a transient decrease in body weight gain accompanied by

decreased food consumption. Red blood cell counts, hemoglobin

concentration, and hematocrit values were slightly decreased in males

exposed at 3.0 ppm (at 4 weeks only), but no effects were observed in

these males at 13 weeks or in females at either interval. No exposure-

related gross or histologic findings were observed at levels up to and

including 3.0 ppm. Exposure at 10 ppm for 3 days caused 40% mortality

in females but no mortality in males. Exposure at 10 ppm for 4 weeks

caused 80% death in females

creased in males

exposed at 3.0 ppm (at 4 weeks only), but no effects were observed in

these males at 13 weeks or in females at either interval. No exposure-

related gross or histologic findings were observed at levels up to and

including 3.0 ppm. Exposure at 10 ppm for 3 days caused 40% mortality

in females but no mortality in males. Exposure at 10 ppm for 4 weeks

caused 80% death in females. Both males and females exposed at 10 ppm

had coagulative necrosis in the tubules of the kidneys and pulmonary

congestion was observed in the females that died. No histologic

findings related to dosing were apparent in the rats exposed for 2

weeks at 5 ppm; an increase in the BUN and alkaline phosphatase were

observed in males but not females exposed at 5 ppm. An LEL for

subchronic exposure (13 weeks) was not established in this study. The

no-observed adverse effect level (NOAEL) for 13 weeks was 3 ppm (HDT).

An LEL of 10 ppm for 4 weeks was based on lethality (4/5 deaths for

females) due to the sharp dose-response curve.

3. Chronic toxicity/carcinogenity. In a 2-year rat feeding study,

diets were treated with Phostoxin pellets at 48 and 90 gm/metric ton,

fumigated for 48 hours and 72 hours, mixed for 2 hours, and then

aerated for one hour. The feed was then stored frozen in small sealed

containers until used as laboratory rat feed. Sixteen separate batches

of feed were treated utilizing this methodology over the 2-year period.

Samples of diet were taken to determine phosphine at the time the feed

was removed from the freezer. Phosphine levels ranged from 0.2 to 7.5

ppm and averaged approximately 1 ppm. The amounts of phosphine that

remained in the feed offered to the rats as food was not measured (but

would be expected to be less because of dissipation). Therefore, the

actual dosages in this study are unknown. Two groups of 60 rats each

(30 males and 30 females) were used, one as treatment group and other

as controls

phine levels ranged from 0.2 to 7.5

ppm and averaged approximately 1 ppm. The amounts of phosphine that

remained in the feed offered to the rats as food was not measured (but

would be expected to be less because of dissipation). Therefore, the

actual dosages in this study are unknown. Two groups of 60 rats each

(30 males and 30 females) were used, one as treatment group and other

as controls. The rats were observed for the effects on growth, food

consumption, survival, morbidity, hematology, blood chemistry and gross

and microscopic pathology. No differences were seen between the

controls and the treated animals for any toxicity parameter. No

increased oncogenicity resulted from fumigation residues. The study was

not considered guideline since toxicity, secondary to phosphine

residues, is not possible when aeration is adequate. However, the study

shows that toxic levels of residues were not achieved even with the

excessive fumigation treatment rates.

In a chronic/oncogenicity study, Charles River Fischer CDF Rats

(60/sex/group) were exposed, under dynamic chamber conditions, to 0,

0.3, 1 and 3 ppm of phosphine. The rats were kept under standard

laboratory conditions, observed twice daily and sacrificed (10/sex/

group) during week 52 of the study. Body weights; food consumption;

routine hematologic, serum biochemical and urinary analyses were all

comparable to control animals. There were no adverse effects observed

for the initial 12 month period. Body weights;

s, to 0,

0.3, 1 and 3 ppm of phosphine. The rats were kept under standard

laboratory conditions, observed twice daily and sacrificed (10/sex/

group) during week 52 of the study. Body weights; food consumption;

routine hematologic, serum biochemical and urinary analyses were all

comparable to control animals. There were no adverse effects observed

for the initial 12 month period. Body weights;

food consumption; routine hematologic, serum biochemical and urinary

analyses were all comparable to control animals. Ophthalmological

observations, gross pathology, organ weights and histopathology

indicated no adverse effects from the phosphine exposures. The NOAEL

for the 52 week period was 3.0 ppm, the HDT.

4. Mutagencity. In a Salmonella typhimurium reverse gene mutation

assay, the test was negative with hydrogen phosphide (PH3)

in all strains up to cytotoxic concentrations (488 ppm/plate

+/-S9).

i. Chromosome aberrations. In an in vitro cytogenetic assay with

Chinese hamster ovary (CHO) cells phosphine was positive at 2,500 and

5,000 ppm without S9 activation. This resulted in a significant but not

dose-related increases in the frequency of cells with structural

chromosome aberrations. Significant clastogenic effects were also noted

at 2,500 ppm with S9 activation but not at the HDT (5,000 ppm).

ii. Other genotoxic mechanisms. In an in vivo unscheduled DNA

Synthesis (UDS) in primary rat hepatocytes, the test was negative in

male Fischer rats exposed via inhalation to PH3 doses of 0,

4.8, 13, 18 or 23 ppm (equiv. to 0, 11.4, 30.8, 42.6 or 54.5 mg/

m3, respectively) for 6 hours. Overt toxicity (i.e.,

difficulty in breathing) but no target cell cytotoxicity was observed

at the HTD.

Based on the findings reported by Garry et al., (1989) that

pesticide applicators exposed to phosphine had increased levels of

chromosome damage, the USEPA sponsored a series of acute (Kligerman et

al.,1994a) and subacute (Kligerman et al., 1994b) inhalation

cytogenetic studies with phosphine

t toxicity (i.e.,

difficulty in breathing) but no target cell cytotoxicity was observed

at the HTD.

Based on the findings reported by Garry et al., (1989) that

pesticide applicators exposed to phosphine had increased levels of

chromosome damage, the USEPA sponsored a series of acute (Kligerman et

al.,1994a) and subacute (Kligerman et al., 1994b) inhalation

cytogenetic studies with phosphine. A summary of these studies are as

follows:

(a) Phosphine was negative for the induction of micronucleated

polychromatic erythrocytes (MPE) in bone marrow cells and splenocytes

and negative for the induction of sister chromatid exchange or

chromosomal aberrations in splenocytes of CD-1 male mice exposed by

inhalation to 0, 5, 10 or 15 ppm for 6 hours. Overt toxicity,

manifested as lethargy and shallow breathing was seen at the HDT. There

was a dose-related and significant reduction of splenocyte cell cycling

at all levels, which indicates that phosphine was cytotoxic to

splenocytes. There was, however, no adverse effect on bone marrow cells

(Kligerman, et al., 1994).

(b) Male B6C3F1 mice and male F344 rats were exposed by inhalation

to 0, 1.25, 2.5 or 5.0 ppm phosphine, 6 hours/day, 5 days/week over an

11-day period. Bone marrow cells and/or peripheral blood lymphocytes

were harvested and examined for sister chromatid exchanges and

chromosomal aberrations (mouse and rat peripheral blood lymphocytes)

and for MPEs (rat bone marrow and mouse bone marrow and peripheral

blood lymphocytes). In addition, B6C3F1 males were exposed via

inhalation to 0 or 5 ppm as above over a 12-day period and mated with

untreated females in a dominant lethal assay. Results show that

phosphine was not genotoxic at any endpoint.

iii. Additional in vivo data summarized below were available for

review:

ymphocytes)

and for MPEs (rat bone marrow and mouse bone marrow and peripheral

blood lymphocytes). In addition, B6C3F1 males were exposed via

inhalation to 0 or 5 ppm as above over a 12-day period and mated with

untreated females in a dominant lethal assay. Results show that

phosphine was not genotoxic at any endpoint.

iii. Additional in vivo data summarized below were available for

review:

(a) Following subchronic inhalation exposure (0, 0.3, 1.0 or 4.5

ppm, 6 hours/ day, 5 days/week for 13 weeks) but not acute inhalation

exposure (0 or 5.5 ppm, 2 weeks, 6 hours/day, 5 days/week for 2 weeks),

phosphine at 4.5 ppm caused a statistically significant increase in

micronucleus induction in the spleen lymphocytes and bone marrow cells

of Balb-c male and female mice. There was, however, no increase in gene

mutations at the hypoxanthine guanine phosphoribosyl transferase locus

in the recovered spleen lymphocytes.

(b) After 6 hours of inhalation exposure, phosphine, at the HDT (19

ppm) induced a significant increase in chromosomal aberrations in the

bone marrow of Sprague Dawley male rats but not in the female rats. The

effect is considered equivocal because increased chromosomal aberration

frequencies were only seen in high-dose males with severely reduced

mitotic indices (MIs). Females did not show increased chromosome

aberrations and did not have decreased MIs. There was also no effect on

peripheral lymphocytes.

al aberrations in the

bone marrow of Sprague Dawley male rats but not in the female rats. The

effect is considered equivocal because increased chromosomal aberration

frequencies were only seen in high-dose males with severely reduced

mitotic indices (MIs). Females did not show increased chromosome

aberrations and did not have decreased MIs. There was also no effect on

peripheral lymphocytes.

(c) In an Australian study of workers exposed to phosphine, 31

phosphine fumigators and 21 controls, all employed at the New South

Wales Grain Corporation, were examined for micronucleus incidence in

peripheral blood lymphocytes and their concentrated urine was assessed

for mutagenicity in TA100 and TA98 strains of S. typhimurium. In

addition, serum bile acids were measured. The subjects, all males, were

matched for medication, X-ray exposure within the past year and smoking

habits. There was no indication how often the fumigators were exposed,

or the most recent exposure date or the length of the various

fumigators employed. No individual data were presented to identify if

certain individuals showed unusually high micronuclei incidence, or

presence of mutagens in the urine.

Urine samples were concentrated 75-fold and the procedure of

Yamaski and Ames (1977) was used to test mutagenicity to TA100 and TA98

in the presence or absence of metabolic activation (S9). There was no

increase in the mutagenicity of urine from the fumigators (N-27) vs

controls (N=-19) in this assay.

Serum bile acids showed no changes related to phosphine exposure.

Cholesterol and some liver enzymes (gamma-glutamyl transferase were

elevated in the exposed group. Micronuclei formation was measured in

isolated peripheral blood lymphocytes cultured for 44 hours in the

presence of phytohemagglutinin to stimulate mitosis, arrested at

metaphase with cytochalasin-B and harvested by cytocentrifugation after

72 hours in culture

es related to phosphine exposure.

Cholesterol and some liver enzymes (gamma-glutamyl transferase were

elevated in the exposed group. Micronuclei formation was measured in

isolated peripheral blood lymphocytes cultured for 44 hours in the

presence of phytohemagglutinin to stimulate mitosis, arrested at

metaphase with cytochalasin-B and harvested by cytocentrifugation after

72 hours in culture. The micronucleus incidence was comparable among

the fumigators and the control groups (overall MI for fumigators = 6.9

vs 7.1 for controls).

Phosphine is not mutagenic in bacteria but is clastogenic in vitro.

Both the negative Ames test and the positive CHO cell chromosome assay

are consistent with the in vitro test results for zinc phosphide.

Studies conducted in vivo indicate that phosphine is not clastogenic in

mice or rats and does not cause dominant lethal mutations in mice

following acute exposures for up to 2 weeks. There is, however,

evidence that inhalation exposures of phosphine for up to 13 weeks

induced significant clastogenic and/or an euploidogenic effects in male

and female mice. The biological relevance of this finding can not be

fully ascertained until the results of the 2-year rat inhalation study

currently underway are submitted and reviewed.

5. Neurotoxicity. In an acute neurotoxicity study, 11

Crl:CDBR VAF/Plus rats/sex/exposure group were

exposed to 0, 20, 30, or 40 ppm of phosphine (1% a.i. in nitrogen) for

four hours. Each treatment group was exposed on a different day, with

the first exposure occurring six days prior to the final exposure. 11

rats/sex/exposure group were selected for functional observational

battery (FOB) and motor activity (MA) testing prior to and following

exposure, and on days 7 and 14 post-exposure; six rats/sex/exposure

group were perfused for neuropathology. All animals survived to

scheduled termination. There were no exposure-related clinical signs

xposure occurring six days prior to the final exposure. 11

rats/sex/exposure group were selected for functional observational

battery (FOB) and motor activity (MA) testing prior to and following

exposure, and on days 7 and 14 post-exposure; six rats/sex/exposure

group were perfused for neuropathology. All animals survived to

scheduled termination. There were no exposure-related clinical signs.

FOB and MA parameters were characterized by variability both within and

among control and exposed groups; this variability (which may be partly

due to the unbalanced treatment schedule) confounded interpretation of

some of

the results. Palpebral closure was noted in some exposed groups on day

1 and was significant in females exposed to 30 and 40 ppm and in males

at 20 and 40 ppm. Body temperatures were significantly lowered for

males and females on day 1 in all exposure groups. The remainder of the

differences in the FOB parameters were random statistical variations

that occurred both pre- and post-test, were not dose related, and were

not consistent between the sexes. Motor activity (horizontal, vertical,

total distance, and stereotypic time) was decreased at 20, 30, and 40

ppm, primarily during the 10 and 20 minute post-exposure time intervals

(data comparing motor activity for the entire 30-minute assessment

period was neither presented nor analyzed). With one exception, these

reductions no longer occurred at 7 or 14 days after exposure. For males

during the first 10-minute post-exposure interval, horizontal activity

decreased significantly by 76.4, 71.7 and 83.8% in the 20, 30, and 40

ppm groups, respectively. Males in the 20 ppm group had the following

decreases in horizontal activity: 76.4%, 77.6% (both statistically

significant), and 89.4% (non-statistically significant) during the 10,

20, and 30 minute intervals, respectively

les

during the first 10-minute post-exposure interval, horizontal activity

decreased significantly by 76.4, 71.7 and 83.8% in the 20, 30, and 40

ppm groups, respectively. Males in the 20 ppm group had the following

decreases in horizontal activity: 76.4%, 77.6% (both statistically

significant), and 89.4% (non-statistically significant) during the 10,

20, and 30 minute intervals, respectively. For females during the first

10-minute post-exposure interval, horizontal activity decreased

significantly by 71.3, 48.0, and 83.5% in the 20, 30, and 40 ppm

groups, respectively. Females in the 20 ppm group had the following

decreases in horizontal activity: 71.3%, 85.8% (both significant), and

54.1% (non-statistically significant) during the 10, 20, and 30 minute

intervals, respectively. Similar decreases occurred for both sexes for

vertical activity, total distance, and stereotypic time. No phosphine-

related neuropathological changes were observed in any exposure group.

Significant increases in absolute and relative (body and brain weights)

adrenal gland weights in males from the 40 ppm group were of

questionable biological significance and did not show a concentration-

response relationship. The significant decrease in temperature and

motor activity, seen at all exposure levels in spite of the flaws in

the study, are considered treatment-related. The LOEL for

neurobehavioral findings is 20 ppm based on decreased body temperatures

and decreased motor activity in males and females. The NOAEL is BE VAF/Plus rats/sex/exposure group were

exposed to phosphine (1% a.i. in nitrogen) for six hours/day, 5 days/

week for approximately 90 days at 0, 0.3, 1, or 3 ppm. An additional

six rats/sex were assigned to the 0 and 3 ppm groups for a 2-week

recovery group. Eleven rats/sex/exposure group were assigned for

neurobehavioral evaluations. Six of the eleven rats/sex/exposure group

were designated for neuropathological evaluations. No exposure-related

deaths occurred in this study

six hours/day, 5 days/

week for approximately 90 days at 0, 0.3, 1, or 3 ppm. An additional

six rats/sex were assigned to the 0 and 3 ppm groups for a 2-week

recovery group. Eleven rats/sex/exposure group were assigned for

neurobehavioral evaluations. Six of the eleven rats/sex/exposure group

were designated for neuropathological evaluations. No exposure-related

deaths occurred in this study. Body weights were slightly higher in

high-concentration males (2.4%) and females (1.2%) after 13 weeks of

treatment, and became equal or less than the control body weights after

the 2 week recovery period. Palpebral closure was consistently

increased in high-concentration animals compared to controls. The

increase was significant (p 0.05) in high-concentration

males at week 4 and was exposure related. The increased palpebral

closure in high-concentration females was not significantly different

from the control group. The incidence of high-concentration males found

sleeping was consistently higher than the controls and was

significantly higher (p 0.05) at week 4. The sleep

incidence in males showed an exposure effect at weeks 4 and 13. A

similar trend was observed in females, but the differences were not

statistically significant. Body temperatures of high-concentration

males were consistently lower than the controls and reached statistical

significance (p 0.05) at week 13. The decreased body

temperature was exposure- related at weeks 4 and 13. Females did not

show a treatment-related change in body temperature. The horizontal and

vertical motor activities were significantly lower in high-

concentration males than the control group at week 13, and were

consistently, but not significantly lower at other time intervals.

Motor activity measurements in females were compromised by high

variations and significant decreases in the high-concentration group at

the pretest interval. There were no treatment-related findings at

necropsy or during the neurohistopathological examination of collected

tissues

es than the control group at week 13, and were

consistently, but not significantly lower at other time intervals.

Motor activity measurements in females were compromised by high

variations and significant decreases in the high-concentration group at

the pretest interval. There were no treatment-related findings at

necropsy or during the neurohistopathological examination of collected

tissues. The effects seen in high-concentration males that could be

treatment-related are slight, but are consistent and mutually

supportive. The effects in females either did not occur, were not

statistically significant, or were compromised by variations in pretest

measurements. Due to the equivocal nature of the effects seen in high-

concentration males, and the lack of effects seen in females, the

tentative NOAEL for systemic/neurobehavioral findings is 3.0 ppm for

males and females, a LOEL was not determined in this study. Since the

procedures used in this study have not been validated, and since

positive effects may be obscured by insensitive methods, the NOAEL is

tentative and will be re-evaluated upon receipt of information

requested from the sponsor. It must be noted that the Agency has asked

for additional information regarding this study and has not accepted

the study until the requested data are submitted and reviewed.

B. Toxicological Endpoints

1. Acute toxicity. The acute dietary endpoint is based upon the

results of the 90-day inhalation study. The dose and endpoint for risk

assessment was 5 ppm or 1.8 milligrams/kilogram/day (mg/kg/day) based

on the lack of treatment-related effects following 15 days of exposure.

This includes a 100 fold Uf to account for inter and intra species

variation.

2. Short - and intermediate - term toxicity. Based on the use

pattern and the fact that phosphine is a gas, an end-point and risk

assessment were not conducted for short- and intermediate-term, oral or

dermal exposures.

3. Chronic toxicity

ed

on the lack of treatment-related effects following 15 days of exposure.

This includes a 100 fold Uf to account for inter and intra species

variation.

2. Short - and intermediate - term toxicity. Based on the use

pattern and the fact that phosphine is a gas, an end-point and risk

assessment were not conducted for short- and intermediate-term, oral or

dermal exposures.

3. Chronic toxicity. EPA has established the chronic reference

dose (RfD) for phosphine at 0.0113 mg/kg/day. This RfD is based on an

interim report (one year) for a 2-year chronic/oncogenicity inhalation

toxicity in rats. The dose for the risk assessment was a NOAEL=3 ppm =

0.004 mg/L=1.13 mg/kg/day. A 100 fold Uf was applied to account for

inter and intra species variation.

4. Carcinogenicity. The results of a non-guideline 2-year rat

feeding study did not indicate a carcinogenic concern. Additionally, an

interim (one year) report for a 2-year inhalation carcinogenicity study

has been reviewed and does not indicate a carcinogenic concern. The

final report was submitted to the Agency in November, 1998 and is being

reviewed; however, it is unlikely to change the Agency's evaluation of

phosphine's carcinogenic potential.

C. Exposures and Risks

1. From food and feed uses. Tolerances have been established under

(40 CFR 180.225 (a) and (b), 185.200, 186.200, 180.375, 185.3800, and

186.3800) for the residues of phosphine, in or on a variety of raw

agricultural

ricultural commodities and processed foods that confirm, with

adequate aeration (48 hours is required) there will not be finite

residues in or on food commodities. Still the FDA does at times sample

RACs before the further processing described above occurs and there is

the potential that small amounts of unreacted phosphine residues of up

to 0.1 ppm could be observed in one of the RACs listed. All aluminum

and magnesium phosphide product labels are carefully reviewed to

restrict direct addition of the fumigant to commodities that are

further processed in a manner that it would preclude the possibility of

unreacted fumigant being in or on the food supply presented to the

consumer. Risk assessments were conducted by EPA to assess dietary

exposures and risks from phosphine as follows:

i. Acute exposure and risk. Acute dietary risk assessments are

performed for a food-use pesticide if a toxicological study has

indicated the possibility of an effect of concern occurring as a result

of a one day or single exposure. Dietary exposure to aluminum and

magnesium phosphide can potentially occur via residues of phosphine gas

remaining in treated commodities. A large number of studies involving

numerous types of raw agricultural commodities and processed

commodities submitted to the Agency for establishment of food

tolerances indicate that residues of phosphine gas will be non-

detectable with adequate aeration. One of these studies involved the

analysis of 49 different processed foods, with all residues being

[email protected]

Electronic comments must be submitted as an ASCII file avoiding the

use of special characters and any form of encryption. Comment and data

will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file

format. All comments and data in electronic form must be identified by

the docket control number [OPP-300865]. Electronic comments on this

proposed rule may be filed online at many Federal Depository Libraries.

VII. Regulatory Assessment Requirements

the

use of special characters and any form of encryption. Comment and data

will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file

format. All comments and data in electronic form must be identified by

the docket control number [OPP-300865]. Electronic comments on this

proposed rule may be filed online at many Federal Depository Libraries.

VII. Regulatory Assessment Requirements

Under Executive Order 12866 (58 FR 51735, October 4, 1993), this

action is not a ``significant regulatory action'' and since this action

does not impose any information collection requirements subject to

approval under the Paperwork Reduction Act, 44 U.S.C. 3501 et. seq., it

is not subject to review by the Office of Management and Budget. In

addition, this action does not impose any enforceable duty, or contain

any ``unfunded mandates'' as described in Title II of the Unfunded

Mandates Reform Act of 1995 (Public Law 104-4), or require prior

consultation as specified by executive Order 12875 (58 FR 58093,

October 28, 1993), or special considerations as required by Executive

Order 12898 (59 FR 7629, February 16, 1994).

Pursuant to the requirements of the Regulatory Flexibility Act

(Public Law 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator

has determined that regulations establishing exemptions from tolerance

requirements do not have a significant economic impact on a substantial

number of small entities. A

certification statement explaining the factual basis for this

determination was published in the Federal Register of May 4, 1981 (46

FR 24950).

A. Executive Order 12875

, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator

has determined that regulations establishing exemptions from tolerance

requirements do not have a significant economic impact on a substantial

number of small entities. A

certification statement explaining the factual basis for this

determination was published in the Federal Register of May 4, 1981 (46

FR 24950).

A. Executive Order 12875

Under Executive Order 12875, entitled Enhancing Intergovernmental

Partnerships (58 FR 58093, October 28, 1993), EPA may not issue a

regulation that is not required by statute and that creates a mandate

upon a State, local or tribal government, unless the Federal government

provides the funds necessary to pay the direct compliance costs

incurred by those governments. If the mandate is unfunded, EPA must

provide to the Office of Management and Budget (OMB) a description of

the extent of EPA's prior consultation with representatives of affected

State, local and tribal governments, the nature of their concerns,

copies of any written communications from the governments, and a

statement supporting the need to issue the regulation. In addition,

Executive Order 12875 requires EPA to develop an effective process

permitting elected officials and other representatives of State, local

and tribal governments ``to provide meaningful and timely input in the

development of regulatory proposals containing significant unfunded

mandates.''

Today's proposed rule does not create an unfunded federal mandate

on State, local or tribal governments. The rule does not impose any

enforceable duties on these entities. Accordingly, the requirements of

section 1(a) of Executive Order 12875 do not apply to this rule.

B. Executive Order 13084

imely input in the

development of regulatory proposals containing significant unfunded

mandates.''

Today's proposed rule does not create an unfunded federal mandate

on State, local or tribal governments. The rule does not impose any

enforceable duties on these entities. Accordingly, the requirements of

section 1(a) of Executive Order 12875 do not apply to this rule.

B. Executive Order 13084

Under Executive Order 13084, entitled Consultation and Coordination

with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not

issue a regulation that is not required by statute, that significantly

or uniquely affects the communities of Indian tribal governments, and

that imposes substantial direct compliance costs on those communities,

unless the Federal government provides the funds necessary to pay the

direct compliance costs incurred by the tribal governments. If the

mandate is unfunded, EPA must provide OMB, in a separately identified

section of the preamble to the rule, a description of the extent of

EPA's prior consultation with representatives of affected tribal

governments, a summary of the nature of their concerns, and a statement

supporting the need to issue the regulation. In addition, Executive

Order 13084 requires EPA to develop an effective process permitting

elected and other representatives of Indian tribal governments ``to

provide meaningful and timely input in the development of regulatory

policies on matters that significantly or uniquely affect their

communities.''

Today's proposed rule does not significantly or uniquely affect the

communities of Indian tribal governments. This action does not involve

or impose any requirements that affect Indian Tribes. Accordingly, the

requirements of section 3(b) of Executive Order 13084 do not apply to

this rule.

List of Subjects

40 CFR Part 180

Environmental protection, Administrative practice and procedure,

Agricultural commodities, Pesticides and pests, Reporting and

recordkeeping requirements.

40 CFR Part 185

ents. This action does not involve

or impose any requirements that affect Indian Tribes. Accordingly, the

requirements of section 3(b) of Executive Order 13084 do not apply to

this rule.

List of Subjects

40 CFR Part 180

Environmental protection, Administrative practice and procedure,

Agricultural commodities, Pesticides and pests, Reporting and

recordkeeping requirements.

40 CFR Part 185

Environmental protection, Food additives, Pesticides and pests.

40 CFR Part 186

Environmental protection, Animal feeds, Pesticides and pests.

Dated: May 25, 1999.

James Jones

Director, Registration Division.

Therefore, it is proposed that 40 CFR chapter 1 be amended as

follows.

PART 180--[AMENDED]

1. In part 180:

a. The authority citation for part 180 continues to read as

follows:

Authority: 21 U.S.C. 321(q), 346(a) and 371.

b. Section 180.225 is revised to read as follows:

Sec. 180.225 Phosphine; tolerances for residues.

(a) General. (1) Tolerances are established for residues of the

insecticide phosphine in or on the following raw agricultural

commodities resulting from post-harvest fumigation:

------------------------------------------------------------------------

Commodity Parts per million

------------------------------------------------------------------------

Almond, nutmeat...................................... 0.1

Avocadoes............................................ 0.01

Bananas (includes Plantains)......................... 0.01

Barley, grain........................................ 0.1

Brazil nuts.......................................... 0.1

Cabbage, Chinese..................................... 0.01

Cacao bean........................................... 0.1

Cashews.............................................. 0.1

Citrus citron........................................ 0.01

Cocoa bean........................................... 0.1

Coffee, bean, green.................................. 0.1

Corn, field, grain..................................

bbage, Chinese..................................... 0.01

Cacao bean........................................... 0.1

Cashews.............................................. 0.1

Citrus citron........................................ 0.01

Cocoa bean........................................... 0.1

Coffee, bean, green.................................. 0.1

Corn, field, grain................................... 0.1

Corn, pop, grain..................................... 0.1

Cotton, seed, undelinted............................. 0.1

Date, dried.......................................... 0.1

Eggplants............................................ 0.01

Endive/Ecarole....................................... 0.01

Filberts............................................. 0.1

Grapefruit........................................... 0.01

Kumquats............................................. 0.01

Lemons............................................... 0.01

Lettuce.............................................. 0.01

Limes................................................ 0.01

Mangoes.............................................. 0.01

Legume vegetables (succulent or dried group, 0.01

excluding soybeans).................................

Millet, grain........................................ 0.1

Mushrooms............................................ 0.01

Oats................................................. 0.1

Oranges.............................................. 0.01

Papayas.............................................. 0.01

Peanut, nutmeat...................................... 0.1

Pecans............................................... 0.1

Peppers.............................................. 0.01

Persimmons........................................... 0.01

Pimentos............................................. 0.01

Pistachio............................................ 0.1

Rice, grain.......................................... 0.1

Rye, grain........................................... 0.1

Safflower, seed.....................................

pers.............................................. 0.01

Persimmons........................................... 0.01

Pimentos............................................. 0.01

Pistachio............................................ 0.1

Rice, grain.......................................... 0.1

Rye, grain........................................... 0.1

Safflower, seed...................................... 0.1

Salsify tops......................................... 0.01

Sesame, seed......................................... 0.1

Sorghum, grain....................................... 0.1

Soybeans............................................. 0.1

Sunflower, seed...................................... 0.1

Sweet potatoes....................................... 0.01

Tangelos............................................. 0.01

Tangerines........................................... 0.01

Tomatoes............................................. 0.01

Walnuts.............................................. 0.1

Wheat................................................ 0.1

------------------------------------------------------------------------

(2) Tolerances are established for residues of the fumigant

phosphine in or on all raw agricultural commodities (RAC) resulting

from preharvest treatment of pest burrows in agricultural and non-crop

land areas as listed in the following table:

------------------------------------------------------------------------

Commodity Parts per million

------------------------------------------------------------------------

All RACs resulting from preharvest treatment of pest 0.01

burrows.............................................

------------------------------------------------------------------------

eas as listed in the following table:

------------------------------------------------------------------------

Commodity Parts per million

------------------------------------------------------------------------

All RACs resulting from preharvest treatment of pest 0.01

burrows.............................................

------------------------------------------------------------------------

(3) Residues resulting from fumigation of processed foods:

------------------------------------------------------------------------

Commodity Parts per million

------------------------------------------------------------------------

Processed foods...................................... 0.01

------------------------------------------------------------------------

(4) Residues resulting from fumigation of animal feeds:

------------------------------------------------------------------------

Commodity Parts per million

------------------------------------------------------------------------

Animal feeds......................................... 0.01

------------------------------------------------------------------------

(5) To assure safe use of this pesticide, it must be used in

compliance with the labeling conforming to that registered by the U.S.

Environmental Protection Agency (EPA) under FIFRA. Labeling shall bear

a restriction to aerate the finished food for 48 hours before it is

offered to the consumer, unless EPA specifically determines that a

different time period is appropriate. Where appropriate, a warning

shall state that under no condition should any formulation containing

aluminum or magnesium phosphide be used so that it will come in contact

with any processed food, except processed brewer's rice, malt, and corn

grits stored in breweries for use in the manufacture of beer.

(b) Section 18 emergency exemptions. [Reserved]

(c) Tolerances with regional registrations. [Reserved]

iate, a warning

shall state that under no condition should any formulation containing

aluminum or magnesium phosphide be used so that it will come in contact

with any processed food, except processed brewer's rice, malt, and corn

grits stored in breweries for use in the manufacture of beer.

(b) Section 18 emergency exemptions. [Reserved]

(c) Tolerances with regional registrations. [Reserved]

(d) Indirect or inadvertent residues. [Reserved]

Sec. 180.375 [Removed]

b. Section 180.375 is removed.

PART 185--[AMENDED]

2. In part 185:

a. The authority citation for part 185 continues to read as

follows:

Authority: 21 U.S.C. 346a and 348.

Sec. 185.200 [Removed]

b. Section 185.200 is removed.

Sec. 185.3800 [Removed]

c. Section 185.3800 is removed.

PART 186--[AMENDED]

3. In part 186:

a. The authority citation for part 186 continues to read as

follows:

Authority: 21 U.S.C. 342, 348, and 371.

Sec. 186.200 [Removed]

b. Section 186.200 is removed.

Sec. 186.3800 [Removed]

c. Section 186.3800 is removed.

[FR Doc. 99-14069 Filed 6-8-99; 8:45 am]

BILLING CODE 6560-50-F