[Federal Register Volume 61, Number 125 (Thursday, June 27, 1996)]
[Notices]
[Pages 33511-33520]
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; 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.
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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 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.
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[FR Doc. 96-12991 Filed 5-22-96; 8:45 am]
BILLING CODE 1505-01-D
