Minimal Risk Levels for Priority Substances and Guidance for Derivation; Republication

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Toxic Substances and Disease Registry

[ATSDR-110]

Minimal Risk Levels for Priority Substances and Guidance for

Derivation; Republication

Editorial Note: The document set forth below was originally

published at 61 FR 25873, May 23, 1996, and is reprinted because of

typesetting errors.

AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR),

Department of Health and Human Services (HHS).

ACTION: Notice.

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

SUMMARY: The Comprehensive Environmental Response, Compensation, and

Liability Act (CERCLA) (42 U.S.C. 9604 et seq.), as amended by the

Superfund Amendments and Reauthorization Act (SARA) (Pub. L. 99-499),

requires that ATSDR develop jointly with the U.S. Environmental

Protection Agency (EPA), in order of priority, a list of hazardous

substances most commonly found at facilities on the CERCLA National

Priorities List (NPL) (42 U.S.C. 9604(i)(2)); prepare toxicological

profiles for each substance included on the priority list of hazardous

substances, and to ascertain in the toxicological profiles, significant

human exposure levels (SHELs) for hazardous substances in the

environment, and the associated acute, subacute, and chronic health

effects (42 U.S.C. 9604(i)(3)); and assure the initiation of a research

program to fill identified data needs associated with the substances

(42 U.S.C. 9604(i)(5)). The ATSDR Minimal Risk Levels (MRLs) were

developed in response to the mandate for SHELs and to provide screening

levels for health assessors and other responders to identify

contaminants and potential health effects that may be of concern at

hazardous waste sites and releases.

This notice announces the internal guidance for derivation of MRLs

for priority hazardous substances by ATSDR. The guidance represents the

agency's current approach to deriving MRLs and reflects the most

current scientific assessment. Comments from the public on the process

of deriving MRLs are welcome. The MRLs for a particular substance are

published in the toxicological profile for that substance. A listing of

the current published MRLs is provided at the end of the notice.

ADDRESSES: Comments on this notice should bear the docket control

number ATSDR-110 and should be submitted to: Division of Toxicology,

Agency for Toxic Substances and Disease Registry, Mailstop E-29, 1600

Clifton Road, NE., Atlanta, Georgia 30333.

FOR FURTHER INFORMATION CONTACT: Dr. Selene Chou, Division of

Toxicology, Agency for Toxic Substances and Disease Registry, 1600

Clifton Road, NE., Mailstop E-29, Atlanta, Georgia 30333, telephone

(404)639-6308 or FAX (404)639-6315.

SUPPLEMENTARY INFORMATION: CERCLA requires that ATSDR prepare

toxicological profiles for priority hazardous substances, and to

ascertain significant human exposure levels for these substances in the

environment, and the associated acute, subacute, and chronic health

effects (42 U.S.C. 9604(i)(3)). Minimal Risk Levels (MRLs) were

developed as an initial response to the mandate. Following discussions

with scientists within the HHS and the EPA, ATSDR chose to adopt a

practice similar to that of the EPA's Reference Dose (RfD) and

Reference Concentration (RfC) for deriving substance-specific levels.

An MRL is an estimate of the daily human exposure to a hazardous

substance that is likely to be without appreciable risk of adverse

noncancer health effects over a specified duration of exposure. These

substance- specific estimates, which are intended to serve as screening

levels, are used by ATSDR health assessors and other responders to

identify contaminants and potential health effects that may be of

concern at hazardous waste sites and releases. It is important to note

that MRLs are not intended to define clean-up or action levels for

ATSDR or other Agencies.

The toxicological profiles include an examination, summary, and

interpretation of available toxicological information and epidemiologic

evaluations of a hazardous substance. During the development of

toxicological profiles, MRLs are derived when ATSDR determines that

reliable and sufficient data exist to identify the target organ(s) of

effect, or the most sensitive health effect(s) for a specific exposure

duration for a given route of exposure to the substance. MRLs are based

on noncancer health effects only and are not based on a consideration

of cancer effects. Inhalation MRLs are exposure concentrations

expressed in units of parts per million (ppm) for gases and volatiles,

or milligrams per cubic meter

[[Page 33512]]

(mg/m3) for particles. Oral MRLs are expressed as daily human doses in

units of milligrams per kilogram per day (mg/kg/day).

ATSDR uses the no-observed-adverse-effect-level/uncertainty factor

approach to derive MRLs for hazardous substances. The MRLs are set

below levels that, based on current information, might cause adverse

health effects in the people most sensitive to such substance-induced

effects (Barnes and Dourson 1988; EPA 1990). MRLs are derived for acute

(1-14 days), intermediate (15-364 days), and chronic (365 days and

longer) exposure durations and for the oral and inhalation routes of

exposure. Currently, MRLs for the dermal route of exposure are not

derived because ATSDR has not yet identified a method suitable for this

route of exposure. MRLs are generally based on the most sensitive

substance-induced end point considered to be of relevance to humans.

ATSDR does not use serious health effects (such as irreparable damage

to the liver or kidneys, or birth defects) as a basis for establishing

MRLs. Exposure to a level above the MRL does not mean that adverse

health effects will occur.

MRLs are intended to serve as a screening tool to help public

health professionals decide where to look more closely. They may also

be viewed as a mechanism to identify those hazardous waste sites or

other hazardous substance exposures that are not expected to cause

adverse health effects. Most MRLs contain some degree of uncertainty

because of the lack of precise toxicological information on the people

who might be most sensitive (e.g., infants, elderly, and nutritionally

or immunologically compromised) to the effects of hazardous substances.

ATSDR uses a conservative (i.e., protective) approach to address these

uncertainties, consistent with the public health principle of

prevention. Although human data are preferred, MRLs often must be based

on results of animal studies because relevant human studies are

lacking. In the absence of evidence to the contrary, ATSDR assumes that

humans are more sensitive than animals to the effects of hazardous

substances, and that certain persons may be particularly sensitive.

Thus, the resulting MRL may be as much as a hundredfold below levels

shown to be nontoxic in laboratory animals.

Proposed MRLs undergo a rigorous review process. They are reviewed

by the Health Effects/MRL Workgroup within the Division of Toxicology;

an expert panel of peer reviewers; the agency wide MRL Workgroup, with

participation from other federal agencies, including EPA; and are

submitted for public comment through the toxicological profile public

comment period. Each MRL is subject to change as new information

becomes available concomitant with updating the toxicological profile

of the substance. MRLs in the most recent toxicological profiles

supersede previously published levels. A listing of the current

published MRLs is provided at the end of this notice.

Categories Used to Derive MRLs

The following health effect end points can be used to derive MRLs:

Systemic

Respiratory

Cardiovascular

Gastrointestinal

Hematological

Musculoskeletal

Hepatic

Renal

Endocrine

Dermal

Ocular

Metabolic

Body weight change

Other systemic effects

Immunological and Lymphoreticular

Neurological

Reproductive

Developmental

To provide a better analysis of the toxic potential of the profiled

substance, the same effect can be considered under more than one system

category; for example, behavioral effects in the offspring can be

either neurological or developmental. However, only one system category

per exposure route and duration should be chosen as the basis for

deriving the MRL. If two different effects within two different systems

would result in the same MRL value, the MRL should be derived from the

one that is best supported by data from all exposure routes and

durations.

Classification of End Points as NOAELs, Less Serious LOAELs or

Serious LOAELs

MRLs are derived from no-observed-adverse-effect levels (NOAELs).

In the absence of NOAELs, MRLs can be derived from less serious lowest-

observed-adverse-effect levels (LOAELs). MRLs are not derived from

serious LOAELs. In its 1986-1988 Biennial Report Volume II, ATSDR

defines an adverse health effect as a harmful or potentially harmful

change in the physiologic function, psychologic state, or organ

structure that may result in an observed deleterious health outcome.

Adverse health effects may be manifested in pathophysiologic changes in

target organs, psychologic effects, or overt disease. This definition

is interpreted to indicate that any effect that enhances the

susceptibility of an organism to the deleterious effects of other

chemical, physical, microbiological, or environmental influences should

be considered adverse.

ATSDR acknowledges that a considerable amount of judgement is

required in this process and that, in some cases, there will be

insufficient data to decide whether or not an effect will lead to

significant dysfunction. ATSDR generally will not derive an MRL if no

adverse health effect has been reported in the published peer reviewed

literature in any target organ (e.g., all free standing NOAELs) for a

given duration. However, data from other durations and routes of

exposure may lend support for selecting an appropriate end point to

derive an MRL.

Deciding whether an end point is a NOAEL or a LOAEL depends in part

upon the toxicity that occurs at other doses in the studies evaluated,

and in part upon knowledge regarding the mechanism of toxicity of the

substance. The distinction between less serious and serious LOAEL is

intended to help the users of the toxicological profiles see at what

levels of exposure ``major'' effects begin to appear, and whether the

less serious effects occur at approximately the same levels as serious

effects or at substantially lower levels of exposure. In general, a

dose that evokes failure in a biological system and can lead to

morbidity or mortality (e.g., acute respiratory distress or death) is

referred to as a serious LOAEL. A more specific classification scheme

is as follows.

No Adverse Effects

Weight loss or decrease in body weight gain of less than

10%.

Changes in organ weight of nontarget organ tissues not

associated with abnormal morphologic or biochemical changes.

Increased mortality over controls that is not

statistically significant (p > 0.05).

Some adaptive responses.

Less Serious Adverse Effects

Reversible cellular alterations at the ultrastructural

level (e.g., dilated endoplasmic reticulum) and at the light-

microscopy level (e.g., cloudy swelling, fatty change).

Necrosis (dependent upon location, distribution,

reversibility or the degree of associated dysfunction), metaplasia, or

atrophy with no apparent decrement of organ function.

[[Page 33513]]

Serum chemistry changes, e.g., moderate elevations of

serum aspartate aminotransferase (SGOT), serum alanine aminotransferase

(SGPT).

Weight loss or decrease in body weight gain of 10%-19%.

Some adaptive responses.

Serious Effects

Death

Clinical effects of significant organ impairment (e.g.,

convulsions, icterus, cyanosis).

Morphologic changes in organ tissues that potentially

could result in severe dysfunction (e.g., marked necrosis of

hepatocytes or renal tubules).

Weight loss or decrease in body weight gain of 20% or

greater.

Serum chemistry changes (e.g., major elevations of SGOT,

SGPT)

Major metabolic effects (e.g., ketosis, acidosis,

alkalosis).

Cancer effects.

Additional guidance on the assessment of end-point-specific health

effects is available upon request.

The Adequacy of Database for Derivation of an MRL

It is difficult to provide strict rules governing this

determination. Each profiled substance presents its own unique

situation. The following key points should be considered:

Good quality human data are generally preferred over

animal data.

Only one MRL is derived per exposure period (acute,

intermediate, or chronic) for each route of exposure.

The MRL is generally based on the highest NOAEL (that does

not exceed a LOAEL) or the lowest LOAEL for the most sensitive end

point for that route and exposure period.

Although not a preferred end point for MRL derivation,

decreased body weight gain can be used when the decrease is greater

than 10% and when the study provides some indication that weight loss

is due to a systemic effect of toxicant and not reduced food and/or

water intake.

It is preferable to derive MRLs using data for each

exposure duration. However, when this is not possible because of

limitations of the database for a given duration, an MRL derived for

one duration may sometimes be applicable to MRL(s) for other

duration(s) of the same route based on consideration of the overall

database.

Selection of Most Sensitive Effect

The MRLs are based on the concept that a threshold level

of exposure exists below which no noncancer health effect is likely to

occur, and, therefore, an exposure level protective against the most

sensitive effect would also be protective against all other effects.

The most sensitive effect is the first adverse effect that occurs or is

expected to occur in humans as dose increases. However, information on

the mechanisms of action should be considered when assessing the

significance of the effects. Where the target organ of effect is not

clearly identified, an MRL is usually not derived. However, the lack of

quantitative data for a particular system category does not preclude

derivation of an MRL if other evidence, such as information from human

case studies, toxicokinetics, and other exposure routes, indicates that

this system would not be expected to be most sensitive to the substance

for the exposure route and duration of concern.

Toxicokinetics data enter into consideration when comparing

information across species, routes, and durations for determination of

the most sensitive effect. Comparison of the metabolism of the compound

exhibiting the toxic effect in animals with its metabolism in humans

may affect the choice of the most sensitive end point. Toxicokinetic

differences among species and for various chemical forms of the

compound may help to explain an apparent inconsistency among studies.

Differences across routes of exposure can also be explained by

different rates of absorption, metabolism (both detoxication and

activation), and excretion.

Selection of a Representative, Quality Study for MRL Derivation

ATSDR emphasizes its preference for using data from humans whenever

such data are reliable and appropriate for MRL derivation. However,

human studies must be of sufficient duration and contain an adequate

number of documented exposed individuals to be useful in risk

assessment. In the absence of adequate human studies, animal studies

are used. The author(s) of the study must provide enough information on

the oral dose or inhalation exposure concentration administered to the

treated animals to allow for estimation of an equivalent human oral

dose or inhalation exposure. For both oral and inhalation studies, the

data presented in the study should at least include the air, water, or

food concentration, the duration of exposure, the frequency of exposure

(i.e., per day and per week), the age of the animals, and evidence that

the food and water consumption rates were not abnormal (e.g., from

weight gain data) for an animal of similar age.

Background documents on general factors that ATSDR considers in

evaluating the quality of a study are available upon request. Other

general principles that have been accepted in practice when evaluating

studies include:

Considerations to the exposure scenario more likely to

occur in environmental exposures. For example, drinking water or

feeding studies are preferred over gavage oil studies for oral

exposures.

Determination whether the study data show a dose-response

consistent with other studies.

The following effects are not used for MRL derivation:

Increased incidence of mortality.

Serious LOAELs.

Health effects that occur in test species as a result of

mechanisms, or metabolic processes that are not found in humans (e.g.,

2-globulin nephropathy in male rats).

Spontaneously occurring disorders that are species and

gender related (e.g., chronic progressive nephropathy in male rats).

Effects of unknown biological significance, based on

mechanism of action, that do not affect known target organs.

Cancer effects.

Computation of Inhalation MRLs

1. Extrapolating From Animals to Humans

When animal data is used in the absence of adequate quantitative

human data, exposure concentrations should be converted to human

equivalent concentrations by using dosimetry adjustment in accordance

with EPA (1990), ``Interim Methods for Development of Inhalation

Reference Doses'' (EPA/600/8-90/066A, August 1990). Standard reference

values should be obtained from EPA (1988): ``Recommendations for and

Documentation of Biological Values for Use in Risk Assessment'' (EPA

600-6-87/008, February, 1988).

For inhalation exposures to gases or vapors, it may be necessary to

convert to human equivalent exposures for respiratory effects (e.g.,

using the regional gas dose ratio for the targeted region of the

respiratory tract) or extra-respiratory effects (e.g., using the blood

to air partition coefficient ratio).

For inhalation exposure to particles, it may also be necessary to

convert to human equivalent exposures for respiratory effects (e.g.,

using the regional deposited dose ratio for the targeted region of the

respiratory tract), or extrarespiratory effects (e.g., using the

[[Page 33514]]

regional deposited dose ratio and uptake from the entire respiratory

system).

2. Adjusting From Intermittent to Continuous Dosing

ATSDR defines an MRL as ``an estimate of the daily human exposure

to a hazardous substance that is likely to be without appreciable risk

of adverse noncancer health effects over a specified duration of

exposure''. The ideal study would involve continuous dosing over the

course of the study. If a study did not involve continuous dosing over

the entire exposure period, an adjustment is usually made. The

``intermittent exposure dose'' (either the NOAEL or LOAEL of the

critical effect selected to be used for MRL derivation) is multiplied

by correction factors to adjust for full day and week exposures. For

example, in intermediate (longer than 14 days) or chronic (longer than

364 days) studies in which the experimental animals were dosed for 6

hours a day for 5 days a week, the estimated ``adjusted dose'' becomes:

Adjusted dose = Intermittent dose x (6 hours/24 hours) x (5 days/7

days)

Intermediate and chronic duration inhalation studies are usually

dose-adjusted for day and week exposures; acute duration inhalation

studies can be duration adjusted from intermittent exposures to 24

hours continuous exposure, but are not adjusted to 1 week. For example,

acute studies in which animals were exposed for 6 hours/day for 3 days

can be adjusted as follows:

Adjusted dose = Intermittent dose x (6 hours/24 hours)

However, making duration adjustments may not be appropriate in

every instance. The toxicokinetics and mechanism of action should be

examined to the fullest extent possible before a determination is made

to adjust for intermittent exposures. The following are some factors to

consider in adjusting for dose and duration.

When the critical effects are mainly dependent on the

exposure concentrations and the substance being tested is rapidly

metabolized and/or excreted, dose adjustment is inappropriate.

If the effects being examined are mainly duration

dependent (e.g., longer periods of exposure increase the severity of

the effects being studied) and metabolism/excretion is moderate to

slow, or the study identifies a cumulative effect, duration adjustment

may be appropriate.

3. Converting From Salt to Parent Substance

Salt concentrations or doses are converted to equivalent

concentrations or doses of the parent substance by multiplying by the

molecular weight ratio of parent to salt.

Computation of Oral MRLs

1. Converting From Concentration to Dose

For feeding studies, the equation for the conversion from food

concentrations is:

(ppm in food) x (f/kg body weight) = mg/kg/day

The food consumption factor (f) is kg of food consumed per day.

Unless the food consumption rate and body weights are available,

standard reference values should be obtained from EPA (1988).

For drinking water studies, the equation for conversion from water

concentrations is:

(ppm in water) x (C/kg body weight) = mg/kg/day

The water consumption rate (C) is liters of water consumed per day.

Unless C and body weights are provided in the study, standard reference

values should be obtained from EPA (1988) or EPA (1986), as

appropriate.

2. Converting From Intermittent to Daily Dosing

By definition an MRL is ``an estimate of the daily human exposure

to a hazardous substance that is likely to be without an appreciable

risk of adverse noncancer health effects over a specified duration of

exposure''. If the principal study did not involve daily dosing over

the entire exposure period, an adjustment is usually made. The

``intermittent dose'' is multiplied by the fraction of the study days

over which the test animals were actively dosed. Acute oral studies are

not adjusted to 1 week; intermediate and chronic oral studies are

usually dose-adjusted to full week exposures. For example, for animals

orally dosed weekly 5 days a week, the estimated ``continuous dose''

becomes:

adjusted dose = intermittent dose x (5 days/7 days)

Uncertainty factors and modifying factor

When sufficient human data are not available to allow an accurate

assessment of noncancer health risks, ATSDR may extrapolate from

available information using uncertainty factors (UFs) to account for

different areas of uncertainty in the database to derive MRLs. In

addition, a modifying factor (MF) may be applied to reflect additional

scientific judgement on the database.

MRLs are derived from human equivalent no-observed-adverse-effect

levels and are calculated as follows:

MRL = (NOAEL) HEC / (UF x MF)

When an appropriate NOAEL does not exist, the lowest LOAEL should

be used and a UF is applied for the use of a LOAEL. Additional

uncertainty factors for human variability to protect sensitive

subpopulations, for interspecies extrapolation when animal studies are

used for derivation of MRLs, and for extrapolation across exposure

durations are also used.

The default value for each individual UF is 10; if complete

certainty in data exists, a value of one can be used; and an

intermediate value is three. By multiplying these individual

uncertainty factors, a combined UF is obtained.

The use of UFs and MFs should be based on scientific judgement on a

case-by-case basis. General guidelines are as follows:

Intrahuman variation

An UF of 10 is generally used to account for intrahuman variation.

However, a UF of 3 or 1 may be applied when a large epidemiologic study

or a study of the sensitive population was used.

Interspecies Extrapolation

In the absence of adequate human data, animal data are used; a UF

of 10 is generally used to account for extrapolation from animals to

humans. However, a UF of 3 or 1 may also be used when comparative

toxicological data indicate that similar effects are expected in humans

at comparable exposure levels. For inhalation MRLs, when dosimetry

adjustment is made for converting animal exposure levels to human

equivalent concentrations, a UF of 3 is generally applied to account

for any remaining uncertainty (Jarabek and Segal 1994).

LOAEL to NOAEL Extrapolation

MRLs are derived from NOAELs. In the absence of a NOAEL, the lowest

LOAEL that causes less serious adverse health effects is used, and a UF

of 10 is generally applied. When the less serious LOAEL approaches the

threshold level, that is, only minimal effects are observed

representing an early indication of toxicity, the effect level is

considered to be a minimal LOAEL, and a UF of 3 may be used.

[[Page 33515]]

Extrapolation Across Durations

It is preferable to derive MRLs using data for each exposure

duration. However, when the database supports extrapolation across

acute, intermediate, or chronic exposure durations, a UF may be applied

based on scientific judgement. For example, the chronic inhalation MRL

for chlordane was derived from the intermediate inhalation MRL with an

additional UF of 10 to account for across duration extrapolation; the

chronic inhalation MRL was supported by the limited data on chronic

exposure as well as the data on oral exposure.

Modifying Factor (MF)

An MF greater than zero and up to 10 may be applied to reflect

additional concerns about the database not covered by the UFs. The

default value for MF is 1. An example is the use of an MF of 3 to

account for the incomplete database in deriving the chronic oral MRL

for 4,4'-methylenebis(2-chloroaniline). Another possible consideration

is that if a test substance is known to bioaccumulate, some studies may

overestimate the dose needed to cause effects. In such cases, a

modifying factor may be applied.

EPA RfDs and ATSDR MRLs

The current approach for MRL derivation by ATSDR is similar to the

methods used by EPA to derive Reference Doses (RfDs) and Reference

Concentrations (RfCs) for chronic exposures. The following table shows

the difference in methodology used by ATSDR and EPA in deriving MRLs

and RfDs/RfCs respectively.

As with RfD methodology, in deriving MRLs, ATSDR uses UFs and MFs

to account for extrapolation from animals to humans, from LOAEL to

NOAEL, for intraspecies variation, for across duration extrapolation,

and for professional judgement on the database. In addition, EPA uses a

UF for an incomplete database (EPA 1990) whereas ATSDR incorporates

scientific judgement, including an incomplete database in the MF.

However, ATSDR does not extrapolate across route of exposure at this

time. It is recognized that the EPA derives RfDs as part of its

regulatory decision-making process. Extrapolation across route of

exposure (most commonly using data from inhalation studies to estimate

levels by the oral route) is sometimes used to develop an RfD where

there is inadequate route-specific information.

Because MRLs may be based on more recent data and are derived using

a slightly different methodology, or because MRLs are derived as a

result of different scientific judgement, MRLs and RfDs (or RfCs) for

the same substance are not necessarily of the same value.

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

MRL RfD/RfC

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

Exposure duration.............. Acute Chronic.

Intermediate ..................

Chronic ..................

Route of exposure.............. Oral............... Oral.

Inhalation Inhalation.

UFs used:

Human variability............ Yes................ Yes.

Interspecies extrapolation... Yes................ Yes.

LOAEL to NOAEL............... Yes................ Yes.

Extrapolation across duration Yes................ Yes.

Incomplete database.......... No................. Yes.

Across route extrapolation... No................. Yes.

MF............................. Yes................ Yes.

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

MRLs for Essential Trace Elements

Since many nutritionally essential elements have been found to be

common contaminants at some toxic waste sites, consideration was given

to both essentiality and toxicity when deriving MRLs for these

substances. Special reference was given to background levels and levels

that have been published as Recommended Dietary Allowances (RDA) or

Estimated Safe and Adequate Daily Dietary Intakes (ESADDIs) by the Food

and Nutrition Board of the National Research Council. MRLs should not

be in conflict with the corresponding RDAs and should be protective for

all age groups.

MRLs vs. Ambient Levels

Since MRLs serve as screening tools for health assessors, it is

important to compare MRLs with ambient levels reported in environmental

monitoring studies. When MRLs are lower than ambient levels, the

relevance of the MRLs is in question, and special consideration is

warranted.

Future Approaches

ATSDR is considering the application of physiologically based

pharmacokinetic (PBPK) modeling to enhance understanding of dose and

across-route extrapolations. In addition, ATSDR is evaluating the

utility of Benchmark Dose modelling, to obtain low-incidence response

exposure levels calculated from mathematically fitted dose-response

curves, as an adjunct to the current NOAEL/LOAEL approach in deriving

MRLs.

References

Barnes DG and Dourson M (1988). Reference Dose (RfD): Description

and Use in Health Risk Assessments. Regulatory Toxicology and

Pharmacology 8:471-486.

EPA (1986). Research and Development: Reference Values for Risk

Assessment. (ECAO-CIN-477 September 1986).

EPA (1988). Recommendations for and Documentation of Biological

Values for Use in Risk Assessment. (EPA 600-6-87/008 February 1988).

EPA (1990). Interim Methods for Development of Inhalation Reference

Concentrations. (EPA/600/8-90/066A August 1990).

Jarabek AM and Segal SA. (1994). Noncancer Toxicity of Inhaled Air

Pollutants: Available Approaches for Risk Assessment and Risk

Management. In: Patrick DR, ed. Toxic Air Pollution Handbook. New

York: Van Nostrand Reinhold, pp. 529-541.

Dated: May 17, 1996.

Claire V. Broome,

Deputy Administrator, Agency for Toxic Substances and Disease Registry.

ATSDR Minimal Risk Levels (MRLs) For Hazardous Substances

[March 1996]

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

Substance name CAS No. Route Duration Value Factors End point

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

ACENAPHTHENE...................... 000083-32-9 ORAL................ INTERMEDIATE........ 0.6 mg/kg/day....... 300 Hepatic.

ACETONE........................... 000067-64-1 INHALATION.......... ACUTE............... 26 ppm.............. 9 Neurological.

INHALATION.......... INTERMEDIATE........ 13 ppm.............. 100 Neurological.

INHALATION.......... CHRONIC............. 13 ppm.............. 100 Neurological.

ORAL................ INTERMEDIATE........ 2 mg/kg/day......... 100 Hematological.

ACROLEIN.......................... 000107-02-8 INHALATION.......... ACUTE............... 0.00005 ppm......... 100 Ocular.

INHALATION.......... INTERMEDIATE........ 0.000009 ppm........ 1000 Respiratory.

[[Page 33516]]

ORAL................ CHRONIC............. 0.0005 mg/kg/day.... 100 Hematological.

ACRYLONITRILE..................... 000107-13-1 INHALATION.......... ACUTE............... 0.1 ppm............. 10 Neurological.

ORAL................ ACUTE............... 0.1 mg/kg/day....... 100 Developmental.

ORAL................ INTERMEDIATE........ 0.01 mg/kg/day...... 1000 Reproductive.

ORAL................ CHRONIC............. 0.04 mg/kg/day...... 100 Hematological.

ALDRIN............................ 000309-00-2 ORAL................ ACUTE............... 0.002 mg/kg/day..... 1000 Developmental.

ORAL................ CHRONIC............. 0.00003 mg/kg/day... 1000 Hepatic.

AMMONIA........................... 007664-41-7 INHALATION.......... ACUTE............... 0.5 ppm............. 100 Respiratory.

INHALATION.......... CHRONIC............. 0.3 ppm............. 10 Respiratory.

ORAL................ INTERMEDIATE........ 0.3 mg/kg/day....... 100 Other.

ANTHRACENE........................ 000120-12-7 ORAL................ INTERMEDIATE........ 10 mg/kg/day........ 100 Hepatic.

ARSENIC........................... 007440-38-2 ORAL................ CHRONIC............. 0.0003 mg/kg/day.... 3 Dermal.

BENZENE........................... 000071-43-2 INHALATION.......... ACUTE............... 0.05 ppm............ 300 Immunological.

BIS (2-CHLORO-ETHYL) ETHER........ 000111-44-4 INHALATION.......... INTERMEDIATE........ 0.02 ppm............ 1000 Body Weight.

BIS (CHLOROMETHYL) ETHER.......... 000542-88-1 INHALATION.......... INTERMEDIATE........ 0.0003 ppm.......... 100 Respiratory.

BORON............................. 007440-42-8 ORAL................ INTERMEDIATE........ 0.01 mg/kg/day...... 1000 Developmental.

BROMODICHLOROMETHANE.............. 000075-27-4 ORAL................ ACUTE............... 0.04 mg/kg/day...... 1000 Hepatic.

ORAL................ CHRONIC............. 0.02 mg/kg/day...... 1000 Renal/Urinary

BROMOFORM......................... 000075-25-2 ORAL................ ACUTE............... 0.6 mg/kg/day....... 100 Neurological.

ORAL................ CHRONIC............. 0.2 mg/kg/day....... 100 Hepatic.

BROMOMETHANE...................... 000074-83-9 INHALATION.......... ACUTE............... 0.05 ppm............ 100 Neurological.

INHALATION.......... INTERMEDIATE........ 0.05 ppm............ 100 Neurological.

INHALATION.......... CHRONIC............. 0.005 ppm........... 100 Neurological.

ORAL................ INTERMEDIATE........ 0.003 mg/kg/day..... 100 Gastrointestinal.

CADMIUM........................... 007440-43-9 INHALATION.......... CHRONIC............. 0.0002 mg/m3........ 10 Renal/Urinary.

ORAL................ CHRONIC............. 0.0007 mg/kg/day.... 3 Renal/Urinary.

CARBON DISULFIDE.................. 000075-15-0 INHALATION.......... CHRONIC............. 0.3 ppm............. 30 Neurological.

ORAL................ ACUTE............... 0.01 mg/kg/day...... 300 Hepatic.

CARBON TETRACHLORIDE.............. 000056-23-5 INHALATION.......... ACUTE............... 0.2 ppm............. 300 Hepatic.

INHALATION.......... INTERMEDIATE........ 0.05 ppm............ 100 Hepatic.

ORAL................ ACUTE............... 0.02 mg/kg/day...... 300 Hepatic.

ORAL................ INTERMEDIATE........ 0.007 mg/kg/day..... 100 Hepatic.

CHLORDANE......................... 000057-74-9 INHALATION.......... INTERMEDIATE........ 0.0002 mg/m3........ 100 Hepatic.

INHALATION.......... CHRONIC............. 0.00002 mg/m3....... 1000 Hepatic.

ORAL................ ACUTE............... 0.001 mg/kg/day..... 1000 Developmental.

ORAL................ INTERMEDIATE........ 0.0006 mg/kg/day.... 100 Hepatic.

ORAL................ CHRONIC............. 0.0006 mg/kg/day.... 100 Hepatic.

CHLORFENVIN PHOS.................. 000470-90-6 ORAL................ ACUTE............... 0.002 mg/kg/day..... 1000 Neurological.

ORAL................ INTERMEDIATE........ 0.002 mg/kg/day..... 1000 Lymphoreticular.

ORAL................ CHRONIC............. 0.0007 mg/kg/day.... 1000 Neurological.

CHLOROBENZENE..................... 000108-90-7 ORAL................ INTERMEDIATE........ 0.4 mg/kg/day....... 100 Hepatic.

CHLORODIBROMO-METHANE............. 000124-48-1 ORAL................ ACUTE............... 0.04 mg/kg/day...... 1000 Renal/Urinary.

ORAL................ CHRONIC............. 0.03 mg/kg/day...... 1000 Hepatic.

CHLOROETHANE...................... 000075-00-3 INHALATION.......... ACUTE............... 1300 ppm............ 10 Neurological.

INHALATION.......... INTERMEDIATE........ 76 ppm.............. 100 Body Weight.

CHLOROFORM........................ 000067-66-3 INHALATION.......... ACUTE............... 1 ppm............... 30 Hepatic.

INHALATION.......... INTERMEDIATE........ 0.05 ppm............ 100 Hepatic.

INHALATION.......... CHRONIC............. 0.02 ppm............ 100 Hepatic

ORAL................ ACUTE............... 0.3 mg/kg/day....... 100 Hepatic.

ORAL................ INTERMEDIATE........ 0.1 mg/kg/day....... 100 Hepatic.

ORAL................ CHRONIC............. 0.01 mg/kg/day...... 1000 Hepatic.

CHLOROMETHANE..................... 000074-87-3 INHALATION.......... ACUTE............... 0.5 ppm............. 100 Neurological.

INHALATION.......... INTERMEDIATE........ 0.4 ppm............. 100 Body Weight.

INHALATION.......... CHRONIC............. 0.4 ppm............. 100 Body Weight.

CHLORPYRIFOS...................... 002921-88-2 ORAL................ ACUTE............... 0.003 mg/kg/day..... 10 Neurological.

ORAL................ INTERMEDIATE........ 0.003 mg/kg/day..... 10 Neurological.

CHROMIUM, HEXAVALENT.............. 018540-29-9 INHALATION.......... INTERMEDIATE........ 0.00002 mg/m3....... 10 Respiratory.

INHALATION.......... CHRONIC............. 0.00002 mg/m3....... 10 Respiratory.

COBALT............................ 007440-48-4 INHALATION.......... INTERMEDIATE........ 0.00003 mg/m3....... 1000 Respiratory.

CRESOL, META-..................... 000108-39-4 ORAL................ ACUTE............... 0.05 mg/kg/day...... 100 Respiratory.

CRESOL, ORTHO-.................... 000095-48-7 ORAL................ ACUTE............... 0.05 mg/kg/day...... 100 Neurological.

CRESOL, PARA-..................... 000106-44-5 ORAL................ ACUTE............... 0.05 mg/kg/day...... 100 Neurological.

CYANIDE........................... 000057-12-5 ORAL................ INTERMEDIATE........ 0.05 mg/kg/day...... 100 Reproductive.

[[Page 33517]]

CYCLOTETRAMETH- YLENE TETRANITR- 002691-41-0 ORAL................ ACUTE............... 0.1 mg/kg/day....... 1000 Neurological.

AMINE.

ORAL................ INTERMEDIATE........ 0.05 mg/kg/day...... 1000 Hepatic.

CYCLOTRIMETHY LENETRINITRAMINE 000121-82-4 ORAL................ ACUTE............... 0.06 mg/kg/day...... 100 Neurological.

(RDX).

ORAL................ INTERMEDIATE........ 0.03 mg/kg/day...... 300 Reproductive.

DDT, P,P'-........................ 000050-29-3 ORAL................ ACUTE............... 0.0005 mg/kg/day.... 1000 Developmental.

ORAL................ INTERMEDIATE........ 0.0005 mg/kg/day.... 100 Hepatic.

DI(2-ETHYLHEXYL) PHTHALATE........ 000117-81-7 ORAL................ ACUTE............... 1 mg/kg/day......... 100 Reproductive.

ORAL................ INTERMEDIATE........ 0.4 mg/kg/day....... 100 Developmental.

DI-N-BUTYL PHTHALATE.............. 000084-74-2 ORAL................ INTERMEDIATE........ 0.6 mg/kg/day....... 100 Developmental .

DI-N-OCTYL PHTHALATE.............. 000117-84-0 ORAL................ ACUTE............... 2 mg/kg/day......... 1000 Hepatic.

DIAZINON.......................... 000333-41-5 ORAL................ INTERMEDIATE........ 0.0002 mg/kg/day.... 1000 Developmental.

DICHLORVOS........................ 000062-73-7 INHALATION.......... ACUTE............... 0.002 ppm........... 100 Neurological.

INHALATION.......... INTERMEDIATE........ 0.0003 ppm.......... 100 Neurological.

INHALATION.......... CHRONIC............. 0.00006 ppm......... 100 Neurological.

ORAL................ ACUTE............... 0.004 mg/kg/day..... 1000 Neurological.

ORAL................ INTERMEDIATE........ 0.003 mg/kg/day..... 10 Neurological.

DIELDRIN.......................... 000060-57-1 ORAL................ ACUTE............... 0.00007 mg/kg/day... 1000 Immunological.

ORAL................ CHRONIC............. 0.00005 mg/kg/day... 100 Hepatic.

DIETHYL PHTHALATE................. 000084-66-2 ORAL................ ACUTE............... 7 mg/kg/day......... 300 Reproductive.

ORAL................ INTERMEDIATE........ 6 mg/kg/day......... 300 Hepatic.

DISULFOTON........................ 000298-04-4 INHALATION.......... ACUTE............... 0.006 mg/m3......... 30 Neurological.

INHALATION.......... INTERMEDIATE........ 2E-4 mg/m3.......... 30 Neurological.

ORAL................ ACUTE............... 0.001 mg/kg/day..... 100 Neurological.

ORAL................ INTERMEDIATE........ 9E-5 mg/kg/day...... 100 Developmental.

ORAL................ CHRONIC............. 6E-5 mg/kg/day...... 1000 Neurological.

ENDOSULFAN........................ 000115-29-7 ORAL................ INTERMEDIATE........ 0.002 mg/kg/day..... 100 Immunological.

ORAL................ CHRONIC............. 0.002 mg/kg/day..... 100 Hepatic.

ENDRIN............................ 000072-20-8 ORAL................ INTERMEDIATE........ 0.002 mg/kg/day..... 100 Neurological.

ORAL................ CHRONIC............. 0.0003 mg/kg/day.... 100 Neurological.

EHTYL BENZENE..................... 000100-41-4 INHALATION.......... INTERMEDIATE........ 0.3 ppm............. 100 Developmental.

ETHYLENE GLYCOL................... 000107-21-1 ORAL................ CHRONIC............. 2 mg/kg/day......... 100 Renal/Urinary.

ETHYLENE OXIDE.................... 000075-21-8 INHALATION.......... INTERMEDIATE........ 0.09 ppm............ 100 Renal/Urinary.

FLUORANTHENE...................... 000206-44-0 ORAL................ INTERMEDIATE........ 0.4 mg/kg/day....... 300 Hepatic.

FLUORENE.......................... 000086-73-7 ORAL................ INTERMEDIATE........ 0.4 mg/kg/day....... 300 Hepatic.

FUEL OIL NO. 2.................... 068476-30-2 INHALATION.......... ACUTE............... 0.02 mg/m3.......... 1000 Neurological.

HEXACHLOROBENZENE................. 000118-74-1 ORAL................ ACUTE............... 0.008 mg/kg/day..... 300 Developmental.

ORAL................ INTERMEDIATE........ 0.0003 mg/kg/day.... 300 Reproductive.

ORAL................ CHRONIC............. 0.00002 mg/kg/day... 1000 Developmental.

HEXACHLOROBUTA-DIENE.............. 000087-68-3 ORAL................ INTERMEDIATE........ 0.0002 mg/kg/day.... 1000 Renal/Urinary.

HEXACHLOROCYCLOHEXANE, BETA-...... 000319-85-7 ORAL................ INTERMEDIATE........ 0.0003 mg/kg/day.... 300 Hepatic.

HEXACHLOROCYCLOHEXANE, GAMMA-..... 000058-89-9 ORAL................ ACUTE............... 0.01 mg/kg/day...... 300 Neurological.

ORAL................ INTERMEDIATE........ 0.00004 mg/kg/day... 300 Immunological.

HEXACHLOROETHANE.................. 000067-72-1 INHALATION.......... ACUTE............... 0.5 ppm............. 100 Neurological.

INHALATION.......... INTERMEDIATE........ 0.09 ppm............ 100 Respiratory.

ORAL................ ACUTE............... 1 mg/kg/day......... 100 Hepatic.

ORAL................ INTERMEDIATE........ 0.01 mg/kg/day...... 100 Hepatic.

HYDRAZINE......................... 000302-01-2 INHALATION.......... INTERMEDIATE........ 0.0002 ppm.......... 1000 Hepatic.

ISOPHORONE........................ 000078-59-1 ORAL................ INTERMEDIATE........ 3 mg/kg/day......... 100 Other.

ORAL................ CHRONIC............. 0.2 mg/kg/day....... 1000 Hepatic.

JP-4 JET FUEL..................... 050815-00-4 INHALATION.......... INTERMEDIATE........ 9 mg/m3............. 300 Hepatic.

JP-7 JET FUEL..................... HZ0600-22-T INHALATION.......... CHRONIC............. 0.3 mg/m3........... 300 Hepatic.

KEPONE............................ 000143-50-0 ORAL................ ACUTE............... 0.01 mg/kg/day...... 100 Neurological.

ORAL................ INTERMEDIATE........ 0.0005 mg/kg/day.... 100 Renal/Urinary.

ORAL................ CHRONIC............. 0.0005 mg/kg/day.... 100 Renal/Urinary.

KEROSENE.......................... 008008-20-6 INHALATION.......... INTERMEDIATE........ 0.01 mg/m3.......... 1000 Hepatic.

M-XYLENE.......................... 000108-38-3 ORAL................ INTERMEDIATE........ 0.6 mg/kg/day....... 1000 Hepatic.

MANGANESE......................... 007439-96-5 INHALATION.......... CHRONIC............. 0.0003 mg/m3........ 100 Neurological.

MERCURY, INORGANIC................ HZ0900-19-T ORAL................ ACUTE............... 0.007 mg/kg/day..... 100 Renal/Urinary.

ORAL................ INTERMEDIATE........ 0.002 mg/kg/day..... 100 Renal/Urinary.

MERCURY, METALLIC................. 007439-97-6 INHALATION.......... ACUTE............... 0.00002 mg/m3....... 100 Developmental.

[[Page 33518]]

INHALATION.......... CHRONIC............. 0.000014 mg/m3...... 100 Neurological.

METHOXYCHLOR...................... 000072-43-5 ORAL................ ACUTE............... 0.02 mg/kg/day...... 1000 Reproductive.

ORAL................ INTERMEDIATE........ 0.02 mg/kg/day...... 1000 Reproductive.

METHYL PARATHION.................. 000298-00-0 ORAL................ CHRONIC............. 0.0003 mg/kg/day.... 100 Neurological.

METHYL-T-BUTYL ETHER.............. 001634-04-4 INHALATION.......... ACUTE............... 2 ppm............... 100 Neuorlogical.

INHALATION.......... INTERMEDIATE........ 0.7 ppm............. 100 Neurological.

INHALATION.......... CHRONIC............. 0.7 ppm............. 100 Renal/Urinary.

ORAL................ ACUTE............... 0.4 mg/kg/day....... 100 Neurological.

ORAL................ INTERMEDIATE........ 0.3 mg/kg/day....... 300 Hepatic.

METHYLENE CHLORIDE................ 000075-09-2 INHALATION.......... ACUTE............... 0.4 ppm............. 100 Neurological.

INHALATION.......... INTERMEDIATE........ 0.03 ppm............ 1000 Hepatic.

ORAL................ CHRONIC............. 0.06 mg/kg/day...... 100 Hepatic.

METHYLMERCURIC CHLORIDE........... 000115-09-3 ORAL................ ACUTE............... 0.00012 mg/kg/day... 10 Developmental.

ORAL................ INTERMEDIATE........ 0.00012 mg/kg/day... 10 Developmental.

MIREX............................. 002385-85-5 ORAL................ CHRONIC............. 0.0008 mg/kg/day.... 100 Hepatic.

N-NITROSODI-N-PROPYLAMINE......... 000621-64-7 ORAL................ ACUTE............... 0.095 mg/kg/day..... 100 Hepatic.

NAPHTHALENE....................... 000091-20-3 INHALATION.......... CHRONIC............. 0.002 ppm........... 1000 Respiratory.

ORAL................ ACUTE............... 0.05 mg/kg/day...... 1000 Neurological.

ORAL................ INTERMEDIATE........ 0.02 mg/kg/day...... 300 Hepatic.

NICKEL............................ 007440-02-0 INHALATION.......... INTERMEDIATE........ 0.00004 mg/m\3\..... 100 Respiratory

P-XYLENE.......................... 000106-42-3 ORAL................ ACUTE............... 1 mg/kg/day......... 100 Neurological.

PENTACHLOROPHENOL................. 000087-86-5 ORAL................ ACUTE............... 0.005 mg/kg/day..... 1000 Developmental.

ORAL................ INTERMEDIATE........ 0.001 mg/kg/day..... 1000 Hepatic.

PHENOL............................ 000108-95-2 ORAL................ ACUTE............... 0.6 mg/kg/day....... 100 Developmental.

POLYBROMINATED BIPHENYLS.......... 067774-32-7 ORAL................ ACUTE............... 0.01 mg/kg/day...... 100 Endocrine.

POLYCHLORINATED BIPHENYLS......... 001336-36-3 ORAL................ CHRONIC............. 0.00002 mg/kg/day... 300 Immunological.

PROPYLENE GLYCOL DINITRATE........ 006423-43-4 INHALATION.......... ACUTE............... 0.003 ppm........... 10 Neurological.

INHALATION.......... INTERMEDIATE........ 0.00004 ppm......... 1000 Hematological.

INHALATION.......... CHRONIC............. 0.00004 ppm......... 1000 Hematological.

SELENIUM.......................... 007782-49-2 ORAL................ CHRONIC............. 0.002 mg/kg/day..... 10 Dermal.

SODIUM FLUORIDE................... 007681-49-4 ORAL................ CHRONIC............. 0.05 mg/kg/day...... 10 Musculoskeletal.

STYRENE........................... 000100-42-5 INHALATION.......... CHRONIC............. 0.06 ppm............ 100 Neurological.

ORAL................ INTERMEDIATE........ 0.2 mg/kg/day....... 1000 Hepatic.

TETRACHLOROETHYLENE............... 000127-18-4 INHALATION.......... ACUTE............... 0.2 ppm............. 10 Neurological.

INHALATION.......... CHRONIC............. 0.04 ppm............ 100 Neurological.

ORAL................ ACUTE............... 0.05 mg/kg/day...... 1000 Developmental.

TITANIUM TETRACHLORIDE............ 007550-45-0 INHALATION.......... CHRONIC............. 0.001 mg/m\3\....... 90 Respiratory.

TOLUENE........................... 000108-88-3 INHALATION.......... ACUTE............... 3 ppm............... 30 Neurological.

INHALATION.......... CHRONIC............. 1 ppm............... 30 Neurological.

ORAL................ ACUTE............... 0.8 mg/kg/day....... 300 Neurological.

ORAL................ INTERMEDIATE........ 0.02 mg/kg/day...... 300 Neurological.

TOTAL XYLENES..................... 001330-20-7 INHALATION.......... ACUTE............... 1 ppm............... 100 Neurological.

INHALATION.......... INTERMEDIATE........ 0.7 ppm............. 300 Developmental.

INHALATION.......... CHRONIC............. 0.1 ppm............. 100 Neurological.

ORAL................ INTERMEDIATE........ 0.2 mg/kg/day....... 1000 Renal/Urinary.

TOXAPHENE......................... 008001-35-2 ORAL................ ACUTE............... 0.005 mg/kg/day..... 1000 Hepatic.

ORAL................ INTERMEDIATE........ 0.001 mg/kg/day..... 100 Hepatic.

TRICHLOROETHYLENE................. 000079-01-6 INHALATION.......... ACUTE............... 2 ppm............... 30 Neurological.

INHALATION.......... INTERMEDIATE........ 0.1 ppm............. 300 Neurological.

ORAL................ ACUTE............... 0.5 mg/kg/day....... 100 Developmental.

ORAL................ INTERMEDIATE........ 0.002 mg/kg/day..... 100 Developmental.

VANADIUM.......................... 007440-62-2 INHALATION.......... ACUTE............... 0.0002 mg/m\3\...... 100 Respiratory.

ORAL................ INTERMEDIATE........ 0.003 mg/kg/day..... 100 Renal/Urinary.

VINYL ACETATE..................... 000108-05-4 INHALATION.......... INTERMEDIATE........ 0.01 ppm............ 100 Respiratory.

VINYL CHLORIDE.................... 000075-01-4 INHALATION.......... ACUTE............... 0.5ppm.............. 100 Developmental.

INHALATION.......... INTERMEDIATE........ 0.03 ppm............ 300 Hepatic.

ORAL................ CHRONIC............. 0.00002 mg/kg/day... 1000 Hepatic.

ZINC.............................. 007440-66-6 ORAL................ INTERMEDIATE........ 0.3 mg/kg/day....... 3 Hematological.

ORAL................ CHRONIC............. 0.3 mg/kg/day....... 3 Hematological.

1,1,1-TRICHLOROETHANE............. 000071-55-6 INHALATION.......... ACUTE............... 2 ppm............... 100 Neurological.

[[Page 33519]]

INHALATION.......... INTERMEDIATE........ 0.7 ppm............. 100 Neurological.

1,1,2,2-TETRA-CHLOROETHANE........ 000079-34-5 INHALATION.......... ACUTE............... 1 ppm............... 10 Neurological.

INHALATION.......... INTERMEDIATE........ 0.4 ppm............. 300 Hepatic.

ORAL................ ACUTE............... 0.3 mg/kg/day....... 100 Hepatic.

ORAL................ INTERMEDIATE........ 0.3 mg/kg/day....... 300 Body Weight.

ORAL................ CHRONIC............. 0.3 mg/kg/day....... 300 Body Weight.

1,1,2-TRICHLORO-ETHANE............ 000079-00-5 ORAL................ ACUTE............... 0.3 mg/kg/day....... 100 Neurological.

ORAL................ INTERMEDIATE........ 0.04 mg/kg/day...... 100 Hepatic.

1,1-DICHLORO-ETHENE............... 000075-35-4 INHALATION.......... INTERMEDIATE........ 0.02 ppm............ 100 Hepatic.

ORAL................ CHRONIC............. 0.009 mg/kg/day..... 1000 Hepatic.

1,1-DIMETHYLHYDRAZINE............. 000057-14-7 INHALATION.......... INTERMEDIATE........ 0.000009 ppm........ 1000 Hepatic.

INHALATION.......... CHRONIC............. 0.000009 ppm........ 1000 Hepatic.

1,2,3-TRICHLORO-PROPANE........... 000096-18-4 INHALATION.......... ACUTE............... 0.0003 ppm.......... 100 Respiratory.

ORAL................ INTERMEDIATE........ 0.06 mg/kg/day...... 100 Hepatic.

1,2-DIBROMO-3-CHLOROPROPANE....... 000096-12-8 INHALATION.......... INTERMEDIATE........ 0.0002 ppm.......... 100 Reproductive.

ORAL................ INTERMEDIATE........ 0.002 mg/kg/day..... 1000 Reproductive.

1,2-DICHLORO-ETHANE............... 000107-06-2 INHALATION.......... ACUTE............... 0.2 ppm............. 100 Immunological.

INHALATION.......... CHRONIC............. 0.2 ppm............. 300 Hepatic.

ORAL................ INTERMEDIATE........ 0.2 mg/kg/day....... 300 Renal/Urinary.

1,2-DICHLORO-ETHENE, CIS-......... 000156-59-2 ORAL................ ACUTE............... 1 mg/kg/day......... 100 Hematological.

ORAL................ INTERMEDIATE........ 0.3 mg/kg/day....... 100 Hematological.

1,2-DICHLORO-ETHENE, TRANS-....... 000156-60-5 INHALATION.......... ACUTE............... 0.2 ppm............. 1000 Hepatic.

INHALATION.......... INTERMEDIATE........ 0.2 ppm............. 1000 Hepatic.

ORAL................ INTERMEDIATE........ 0.2 mg/kg/day....... 100 Hepatic.

1,2-DICHLORO-PROPANE.............. 000078-87-5 INHALATION.......... ACUTE............... 0.05 ppm............ 1000 Respiratory.

INHALATION.......... INTERMEDIATE........ 0.007 ppm........... 1000 Respiratory.

ORAL................ ACUTE............... 0.1 mg/kg/day....... 1000 Neurological.

ORAL................ INTERMEDIATE........ 0.07 mg/kg/day...... 1000 Hematological.

ORAL................ CHRONIC............. 0.09 mg/kg/day...... 1000 Hepatic.

1,2-DIMETHYL-HYDRAZINE............ 000540-73-8 ORAL................ INTERMEDIATE........ 0.0008 mg/kg/day.... 1000 Hepatic.

1,3-DICHLORO-PROPENE.............. 000542-75-6 INHALATION.......... INTERMEDIATE........ 0.003 ppm........... 100 Respiratory.

INHALATION.......... CHRONIC............. 0.002 ppm........... 100 Respiratory.

1,3-DINITRO-BENZENE............... 000099-65-0 ORAL................ ACUTE............... 0.008 mg/kg/day..... 100 Reproductive.

ORAL................ INTERMEDIATE........ 0.0005 mg/kg/day.... 1000 Hematological.

1,4-DICHLORO-BENZENE.............. 000106-46-7 INHALATION.......... INTERMEDIATE........ 0.2 ppm............. 100 Hepatic.

ORAL................ INTERMEDIATE........ 0.1 mg/kg/day....... 100 Hepatic.

1-METHYLNAPHTHALENE............... 000090-12-0 ORAL................ CHRONIC............. 0.07 mg/kg/day...... 1000 Respiratory.

2,3,4,7,8-PENTACHLORODIBENZO-FURAN 057117-31-4 ORAL................ ACUTE............... 0.000001 mg/kg/day.. 3000 Immunological.

ORAL................ INTERMEDIATE........ 0.00000003 mg/kg/day 3000 Hepatic.

2,3,7,8-TETRACHLORODIBENZO-P- 001746-01-6 ORAL................ ACUTE............... 0.0000001 mg/kg/day. 1000 Hepatic.

DIOXIN.

ORAL................ INTERMEDIATE........ 0.000000001 mg/kg/ 1000 Reproductive.

day.

ORAL................ CHRONIC............. 0.000000001 mg/kg/ 1000 Reproductive.

day.

2,4,6-TRICHLORO-PHENOL............ 000088-06-2 ORAL................ INTERMEDIATE........ 0.04 mg/kg/day...... 100 Reproductive.

2,4,6-TRINITROTOL-UENE............ 000118-96-7 ORAL................ INTERMEDIATE........ 0.0005 mg/kg/day.... 1000 Hepatic.

2,4-DINITROPHENOL................. 000051-28-5 ORAL................ ACUTE............... 0.01 mg/kg/day...... 100 Body Weight.

2,4-DINITROTOLUENE................ 000121-14-2 ORAL................ ACUTE............... 0.06 mg/kg/day...... 1000 Hematological.

ORAL................ INTERMEDIATE........ 0.05 mg/kg/day...... 100 Reproductive.

[[Page 33520]]

ORAL................ CHRONIC............. 0.002 mg/kg/day..... 100 Hematological.

2,6-DINITROTOLUENE................ 000606-20-2 ORAL................ INTERMEDIATE........ 0.04 mg/kg/day...... 100 Neurological.

4,4'-METHYLENE-BIS (2- 000101-14-4 ORAL................ CHRONIC............. 0.003 mg/kg/day..... 3000 Hepatic.

CHLOROANILINE).

4,6-DINITRO-O-CRESOL.............. 000534-52-1 ORAL................ ACUTE............... 0.004 mg/kg/day..... 100 Neurological.

ORAL................ INTERMEDIATE........ 0.004 mg/kg/day..... 100 Neurological.

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

[FR Doc. 96-12991 Filed 5-22-96; 8:45 am]

BILLING CODE 1505-01-D