[Federal Register Volume 61, Number 101 (Thursday, May 23, 1996)]
[Notices]
[Pages 25873-25882]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-12991]



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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

AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), 
Department of Health and Human Services (HHS).

ACTION: Notice.

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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

[[Page 25874]]

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 (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

[[Page 25875]]

    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.
     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.

[[Page 25876]]

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 
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.

[[Page 25877]]

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.

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

[[Page 25878]]

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.             
                                                    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.............  0.003 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 (CHLORO-ETHYL) 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  Nurological.             
                                                    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.............  0.007 mg/kg/day.....        3  Renal/Urinary.           
CARBON DISULFIDE..................     000075-15-0  INHALATION..........  CHRONIC.............  0.3 ppm.............       30  Neurolgical.             
                                                    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.           

[[Page 25879]]

                                                                                                                                                        
                                                    ORAL................  INTERMEDIATE........  0.0006 mg/kg/day....      100  Hepatic.                 
                                                    ORAL................  CHRONIC.............  0.000 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.............  0.002 mg/kg/day.....     1000  Neurological.            
CHLOROBENZENE.....................     000108-90-7  ORAL................  INTERMEDIATE........  0.4 mg/kg/day.......      100  Hepatic.                 
CHLORODIBROMOMETHANE..............     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.            
                                                    INHALATION..........  CHRONIC.............  0.00002 mg/m3.......       10  Respiratory.             
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/kb/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 gm/kg/day......      100  Reproductive.            
CYCLOTETRAMETHYLENE TETRANITRAMINE     002691-41-0  ORAL................  ACUTE...............  0.1 mg/kg/day.......     1000  Neurological.            
                                                    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.                 

[[Page 25880]]

                                                                                                                                                        
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.           
HEXACHLOROBUTADIENE...............     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...............  0.1 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.           
                                                    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  Neurological.            
                                                    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..........................     000106-64-3  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.                 

[[Page 25881]]

                                                                                                                                                        
TETRACHLOROETHYLENE...............     000127-18-4  INHALATION..........  ACUTE...............  0.2 ppm.............       10  Neurological.            
                                                    INHALATION..........  CHRONIC.............  0.04 PPM............      100  Neurological.            
                                                    ORAL................  ACUTE...............  0.5 mg/kg/day.......     1000  Development.             
TITANIUM TETRACHLORIDE............     007550-45-0  INHALATION..........  CHRONIC.............  0.001 mg/m\3\.......       90  Respiratory.             
TOLUENE...........................    0001108-88-3  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  Development.             
                                                    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  Development.             
                                                    ORAL................  INTERMEDIATE........  0.002 mg/kg/day.....      100  Development.             
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  Development.             
                                                    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.            
                                                    INHALATION..........  INTERMEDIATE........  0.7 ppm.............      100  Neurological.            
1,1,2,2-TETRA-CHLORO-ETHANE.......     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-TRI-CHLORO-ETHANE...........     000079-00-5  ORAL................  ACUTE...............  0.3 mg/kg/day.......      100  Neurological.            
                                                    ORAL................  INTERMEDIATE........  0.04 mg/kg/day......      100  Hepatic.                 
1,1-DI-CHLORO-ETHENE..............     000075-35-4  INHALATION..........  INTERMEDIATE........  0.02 ppm............      100  Hepatic.                 
                                                    ORAL................  CHRONIC.............  0.009 mg/kg/day.....     1000  Hepatic.                 
1,1-DI-METHYL-HYDRAZINE...........     000057-14-7  INHALATION..........  INTERMEDIATE........  0.000009 ppm........     1000  Hepatic.                 
                                                    INHALATION..........  CHRONIC.............  0.000009 ppm........     1000  Hepatic.                 
1,2,3-TRI-CHLORO-PROPANE..........     000096-18-4  INHALATION..........  ACUTE...............  0.0003 ppm..........      100  Respiratory.             
                                                    ORAL................  INTERMEDIATE........  0.06 mg/kg/day......      100  Hepatic.                 
1,2-DI-BROMO-3-CHLORO-PRO-PANE....     000096-12-8  INHALATION..........  INTERMEDIATE........  0.0002 ppm..........      100  Reproductive.            
                                                    ORAL................  INTERMEDIATE........  0.002 mg/kg/day.....     1000  Reproductive.            
1,2-DI-CHLORO-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-DI-CHLORO-ETHENE, CIS-........     000156-59-2  ORAL................  ACUTE...............  1 mg/kg/day.........      100  Hematological.           
                                                    ORAL................  INTERMEDIATE........  0.3 mg/kg/day.......      100  Hematological.           
1,2-DI-CHLORO-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-DI-CHLORO-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-DI-METHYL-HYDRAZINE...........     000540-73-8  ORAL................  INTERMEDIATE........  0.0008 mg/kg/day....     1000  Hepatic.                 

[[Page 25882]]

                                                                                                                                                        
1,3-DI-CHLORO-PROPENE.............     000542-75-6  INHALATION..........  INTERMEDIATE........  0.003 ppm...........      100  Respiratory.             
                                                    INHALATION..........  CHRONIC.............  0.002 ppm...........      100  Respiratory.             
1,3-DI-NITRO-BENZENE..............     000099-65-0  ORAL................  ACUTE...............  0.008 mg/kg/day.....      100  Reproductive.            
                                                    ORAL................  INTERMEDIATE........  0.0005 mg/kg/day....     1000  Hematological.           
1,4-DI-CHLORO-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-PENTA-CHLORO-DI-BENZO-       057117-31-4  ORAL................  ACUTE...............  0.000001 mg/kg/day..     3000  Immunological.           
 FURAN.                                                                                                                                                 
                                                    ORAL................  INTERMEDIATE........  0.00000003 mg/kg/day     3000  Hepatic.                 
2,3,7,8-TETR-ACHLORO-DIBENZO-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-TRI-CHLORO-PHENOL...........     000088-06-2  ORAL................  INTERMEDIATE........  0.04 mg/kg/day......      100  Reproductive.            
2,4,6-TRI-NITROTOL-UENE...........     000118-96-7  ORAL................  INTERMEDIATE........  0.0005 mg/kg/day....     1000  Hepatic.                 
2,4-DI-NITRO-PHENOL...............     000051-28-5  ORAL................  ACUTE...............  0.01 mg/kg/day......      100  Body Weight.             
2,4-DI-NITRO-TOLUENE..............     000121-14-2  ORAL................  ACUTE...............  0.06 mg/kg/day......     1000  Hematological.           
                                                    ORAL................  INTERMEDIATE........  0.05 mg/kg/day......      100  Reproductive.            
                                                    ORAL................  CHRONIC.............  0.002 mg/kg/day.....      100  Hematological.           
2,6-DI-NITRO-TOLUENE..............     000606-20-2  ORAL................  INTERMEDIATE........  0.04 mg/kg/day......      100  Neurological.            
4,4 deg.-METHYL-ENE-BIS (2-            000101-14-4  ORAL................  CHRONIC.............  0.003 mg/kg/day.....     3000  Hepatic.                 
 CHLOROANILINE).                                                                                                                                        
4,6-DI-NITRO-O-CRESOL.............     000534-52-1  ORAL................  ACUTE...............  0.004 mg/kg/day.....      100  Neurological.            
                                                    ORAL................  INTERMEDIATE........  0.004 mg/kg/day.....      100  Neurological.            
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[FR Doc. 96-12991 Filed 5-22-96; 8:45 am]
BILLING CODE 4163-70-P