&EPA
Umtea Stales
Environmental Protection
Agency
Office of Water Regulations
and Standards
Washington. DC 20460
Water Quality
Criteria Methodology
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FINAL REPORT
on
WATER QUALITY CRITERIA METHODOLOGY
to
U.S. ENVIRONMENTAL PROTECTION AGENCY
Criteria and Standards Division
August 6, 1990
Contract No. 68-03-3534
Work Assignment No. H2-52
BATTELLE
Washington Environmental Program Office
2101 Wilson Boulevard, Suite 800
Arlington, Virginia 22201
Revised October 22, 1990
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This report is a work prepared for the United States by
Battelle. In no event shall either the United States or
Battelle have any responsibility or liability for any
consequences of any use, misuse, inability to use, or
reliance upon the information contained herein, nor does
either warrant or otherwise represent in any way the
accuracy, adequacy, efficacy, or applicability of the contents
hereof.
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1.0 BACKGROUND
EPA's water quality criteria are developed under the authority of Section
304(a)(l) of the Clean Water Act which reads as follows:
"The [EPA] Administrator, after consultation with appropriate Federal and State
agencies and other interested persons shall develop and publish, within one year
after the date of enactment of this title (and from time to time thereafter revise)
criteria for water quality accurately reflecting the latest scientific knowledge (A)
on the kind and extent of all identifiable effects on health and welfare including
but not limited to, plankton, fish, shellfish, wildlife, plant life, shorelines,
beaches, esthetics, and recreation which may be expected from the presence of
pollutants in any body of water, including ground water; (B) on the
concentration and dispersal of pollutants, or their by products, through
biological, physical, and chemical processes; and (C) on the effects of pollutants
on biological community diversity, productivity, and stability, including
information on the factors affecting rates of eutrophication and rates of organic
and inorganic sedimentation for varying types of receiving waters."
The Section 304 (a) (1) requirement for development of criteria supports the goal of
fishable swimmable waters given in Section 101 (a)(2) which states that:
"it is the national goal that, wherever attainable, an interim goal of water
quality which provides for the protection and propagation of fish, shellfish, and
wildlife and provides for recreation in and on the water be achieved by July 1,
1983."
The Section 304(a)(l) water quality criteria are issued as guidance to the States.
These criteria are not enforceable regulations. Rather, these criteria present scientific
data and provide guidance on the environmental effects of pollutants which can be
useful in deriving regulatory requirements based on consideration of water quality
impacts. Under the Clean Water Act, these regulatory requirements may include the
promulgation of water quality-based effluent limitations under Section 302, water
quality standards under Section 303, or toxic pollutant effluent standards under
Section 307. The States are responsible for developing State standards. States may
simply adopt EPA's criteria, modify them on a site-specific basis (i.e., develop site-
specific criteria), or use an entirely different number, provided that the new number is
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scientifically defensible. State standards are submitted to EPA for approval, and if
EPA disapproves, either the State must promulgate a new standard, or in rare cases,
EPA may promulgate standards for the State if the State fails to develop acceptable
standards in a timely manner. For example, prompted by the 1987 CWA, EPA is
currently promulgating State toxics standards for certain States which have not done
so.
EPA issues both criteria to protect aquatic life and criteria to protect human
health. This document confines itself to the methodology for developing criteria to
protect human health. The methodology described in this document was published in
the Federal Register on November 28, 1980, "Water Quality Criteria Documents;
Availability, Appendix C - Guidelines and Methodology Used in the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria Documents"
(45 FR 79347). This methodology has been reviewed and approved by EPA's Science
Advisory Board. A copy of these guidelines is included in Appendix A of this
document.
The purpose of human health criteria is to estimate the ambient water
concentration of a pollutant which does not represent a significant risk to the public.
Ambient water quality criteria for human health are primarily based on two types of
biological endpoints: (1) carcinogenicity and (2) toxicity (i.e., all adverse effects other
than cancer). Also, criteria may in some cases be based on organoleptic effects
(thresholds for taste or odor). There are essentially two procedures for assessing
health effects; one which addresses carcinogens and one which addresses non-
carcinogens. The reason for having two methodologies is that, for the purpose of
deriving ambient water quality criteria, carcinogenicity is regarded as a non-threshold
phenomenon, whereas toxicity is regarded as having a threshold below which there
will not be an effect.
Under the assumption that carcinogenicity is a "non-threshold phenomenon,"
there are no "safe" or "no effect" levels, because even extremely small doses are
assumed to elicit a finite increase in the incidence of the response. Therefore, water
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quality criteria for carcinogens are presented as a range of pollutant concentrations
associated with corresponding incremental increases in the risk of developing cancer.
For compounds which do not manifest any apparent carcinogenic effect, the
assumption used to derive a criterion is that the compound has a threshold below
which no effects will be observed. This assumption is based on the premise that a
physiological reserve capacity (or defense mechanism) exists within the organism
which is thought to be depleted before clinical disease ensues. Alternatively, it may
be assumed that the rate of damage will be insignificant over the lifespan of the
organism. Thus, ambient water quality criteria are also derived for non-carcinogenic
chemicals, and presumably result in no-observable-adverse-effect levels (NOAELs) in
human populations.
In some instances, criteria are based on organoleptic characteristics, i.e.,
thresholds for taste or odor. Such criteria are established when insufficient
information is available on toxicologic effects, or when the estimate of the
organoleptic effect level of the pollutant in ambient water is lower than the level
calculated from toxicologic data. It should be recognized that criteria based solely on
organoleptic effects do not necessarily represent approximations of acceptable risk
levels for human health. Development of these criteria will not be discussed further
in this document.
This document describes the methodology used to develop human health criteria
for both carcinogens and non-carcinogens. The methodology used includes four steps:
hazard identification, dose-response assessment, exposure assessment, and a risk
management decision. Each of these steps will be discussed in a separate section
below. The criteria developed from this methodology are published in criteria
documents for each of the compounds or groups of compounds evaluated. These
criteria documents provide the scientific base used to support development of the
criteria. As discussed in more detail below, the methodology was not developed to
assess fish contamination directly, but can be utilized for this purpose. One goal of
this document is to discuss the methodology in detail so that an informed decision can
be made concerning its utility for this purpose.
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2.0 HAZARD IDENTIFICATION
Hazard identification involves gathering and evaluating data on the types of
health injury or disease that may be produced by a chemical, and data on the
conditions of exposure under which injury or disease may be produced. It may also
involve characterization of the behavior of a chemical within the body and the
interactions it undergoes with organs, cells or even part of cells. Data of the latter
types may be of value in answering the ultimate question of whether the forms of
toxicity known to be produced by a substance in one population group or in
experimental settings are also likely to be produced in humans. Hazard identification
is not risk assessment; rather it is simply the process of determining whether exposure
to an agent can cause an increase in the incidence of an adverse health effect. It
includes an associated characterization of the nature and strength of the evidence of
causation.
Information for hazard identification can be obtained from EPA's approved
toxicology data source, the Integrated Risk Information System (IRIS). IRIS is an
electronic data base containing health risk and EPA regulatory information on specific
chemicals. It was developed for EPA staff in response to a growing demand for
consistent risk information on chemical substances for use in decision-making and
regulatory activities. The heart of the IRIS system is its collection of computer files
covering individual chemicals. IRIS can be accessed to obtain summaries of key
toxicological data to be used in hazard identification.
The results of the hazard identification process influence the nature and the
extent of subsequent steps in risk analysis. For example, the endpoint of concern in a
dose-response assessment may be selected based on the most severe adverse effect
identified in the hazard identification.
In the hazard assessment, an attempt is made to include the known relevant
hazard information. The relevant hazard information for a particular compound is
summarized in the criteria document prepared to support the derivation of the criteria
for that compound. Review articles and reports are often used in the process of data
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evaluation and synthesis. Scientific judgement is exercised in the review and
evaluation of the data and in the identification of the adverse effects for which
protective criteria are developed. The criteria documents are peer reviewed by a
committee of scientists familiar with the specific compound(s). These work groups
evaluate the quality of the available data, the completeness of the data summary, and
the validity of the derived criterion. As noted below, EPA is not developing any new
human health criteria at the present time.
In the analysis and organization of the data an attempt is made to be consistent
with respect to the format and the application of acceptable scientific principles.
Evaluation procedures used in the hazard identification process follow the principles
outlined by the National Academy of Sciences in "Drinking Water and Health" (1977),
and the guidelines of the Carcinogen Assessment Group of the U.S. EPA.
Chemicals for which human health criteria have been published by EPA include
most of the 126 toxic priority pollutants listed under Section 307 (a) of the Clean
Water Act (see Table 1). The method used in developing the priority pollutant list is
unclear; however, toxicity and production were considered in the selection process.
EPA has not issued any new human health criteria since 1984, but will issue new
ones as needed; existing criteria are being revised to reflect current science.
The detection limits and methods available for analyzing pollutant concentrations
are not considered in setting water quality criteria. However, for other purposes, EPA
has spent considerable resources in developing standard analytical methods for these
pollutants in a number of matrices, and in extending detection limits to the state of
the art. Analytical methods are published in 40 CFR Part 136, "Guidelines
Establishing Test Procedures for the Analysis of Pollutants Under the Clean Water Act"
(49 Federal Register 2, October 26, 1984). These analytical procedures are used for
compliance monitoring and to express pollutant quantities, characteristics, or
properties in effluent limitations guidelines and ambient water quality standards.
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TABLE 1. LIST OF 126 PRIORITY POLLUTANTS
Acenaphthene
Acrolein
Acrylonitrile
Benzene
Benzidine
Carbon tetrachloride (tetra-
chloromethane)
Chlorobenzene
* 1,2,4-Tri ch1orobenzene
Hexachlorobenzene
1,2-Dichloroethane
1,1-1-Trichloroethane
Hexachloroethane
*1,1-Dichloroethane
1,1,2-Trichloroethane
1,1,2,2,-Tetrach1oroethane
* Chioroethane
Bis(2-chloroethyl)ether
2-Chloroethyl vinyl ether
(mixed)
* 2-Chloronaphthalene
2,4,6-Tri chlorophenol
* Parachlorometacresol
Chloroform(trichloromethane)
2-Chlorophenol
1,2-Di ch1orobenzene
1,3-Dichlorobenzene
1,4-Dichlorobenzene
3,3-Dichlorobenzidine
1,1-Dichloroethylene
1,2-Trans-dichloroethylene
2,4-Dichlorophenol
* 1,2-Dichloropropane
1,3-Dichloropropylene
•# 2,4-Dimethylphenol
* 2,4-Dinitrotoluene
* 2,6-Dinitrotoluene
1,2-Diphyeny1hydrazine
Ethylbenzene
Fluoranthene
# 4-Chlorophenyl phenyl ether
* 4-Bromophenyl phenyl ether
Bi s(2-ch1oroisopropyl)ether
«t Bis (2-chloroethoxy)methane
Methylene chloride (dichloro-
methane)
Vinyl chloride (chloroethylene)
Dieldrin
Chlordane (tech. mixture
& metabolites)
4,4-DDT
4,4-DDE (p.pDOX)
4,4-DDE (p.p-TDE)
Alpha-endosulfan
Beta-endosulfan
Endosulfan sulfate
Endrin
Endrin aldehyde
Methyl chloride (chloro-
methane)
Methyl bromide
Bromoform (tribromomethane)
Dichlorobromomethane
Chlorodibromomethane
Hexachlorobutadi ene
Hexach1orocyc1opentadi ene
Isophorone
4 Naphthalene
Nitrobenzene
* 2-Nitrophenol
* 4-Nitrophenol
2,4-Dinitrophenol
4,6-Di ni tro-o-cresol
N-nitrosodimethylamine
N-nitrosodiphenylamine
N-nitrosodi-n-propylamine
Pentachlorophenol
Phenol (4APP method)
Bis(2-ethylhexyl)phthalate
Butyl benzyl phthalate
Di-n-butyl phthalate
* Di-n-octyl phthalate
Diethyl phthalate
Dimethyl phthalate
Benzo(a)anthracene (1,2
benzanthracene)
Benzo(a)pyrene(3,4-benzo-
pyrene)
3,4-Benzof1uoranthene
Benzo(k)fluoranthane (11,
12-benzof1uoranthene)
Chrysene
Acenaphthylene
Anthracene
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TABLE 1. LIST OF 126 PRIORITY POLLUTANTS (Continued)
Aldrin
Benzo(ghi)perylene (1,12-
benzoperylene)
Fluorene
Phenanthrene
Dibenzo(a.h)anthracene
Indeno(li2,3-cd)pyrene
Pyrene
Tetrach1oroethy1ene
Toluene
Tr i ch1oroethy1ene
Heptachlor
Heptachlor expoxide
Alpha-BHC
Beta-BHC
Gamma-BHC(lindane)
Delta-BHC
PCB-1242
PCB-1254
PCB-1221
PCB-1232
PCB-1248
PCB-1260
PCB-1016
Aroclor 1242
Aroclor 1254
Aroclor 1221
Aroclor 1232)
Aroclor 1248)
Aroclor 1260)
Aroclor 1016)
Toxaphene
Antimony (total)
Arsenic (total)
Asbestos (fibrous)
Beryllium (total)
Cadmium (total)
Chromium (total)
Copper (total)
Cyanide (total)
Lead (total)
Mercury (total)
Nickel (total)
Selenium (total)
Silver (total)
Thallium (total)
Zinc (total)
2,3,7,8-Tetrachlorodibenzo-
p-dioxin (TCOO)
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3.0 DOSE-RESPONSE ASSESSMENT
The human health risks of a substance cannot be determined with any degree of
confidence unless dose-response relationships are quantified, even if the substance is
known to be toxic. Therefore, a dose-response assessment is required before a
criterion can be calculated. The dose-response assessment determines the quantitative
relationship between the amount of exposure to a substance and the onset of toxic
injury or disease. Data for determining dose-response relationships are typically
derived from animal studies, or less frequently, from epidemiologic studies in exposed
populations. Dose-response data for use in calculation of water quality criteria are
taken from the IRIS system, described in the previous section. Data in IRIS are taken
from the literature and peer reviewed within EPA before entering on the system.
The dose-response information needed for carcinogens is an estimate of the
carcinogenic potency of the compound. Carcinogenic potency is defined here as a
general term for a chemical's human cancer-causing potential. This term is often used
loosely to refer to the more specific carcinogenic slope factor. Carcinogenic slope
factor is defined here as an estimate of carcinogenic potency derived using animal
studies or epidemiological data on human exposure. It is based on extrapolation from
typical test exposures at high dose levels over short periods of time to more realistic
low dose levels over a lifetime exposure period by using a linear model. EPA
generally assumes a 70 year lifetime in these calculations. The carcinogenic slope
factor is the estimate of carcinogenic potency which is used in developing the criteria.
This estimate of carcinogenic potency is generally regarded as a conservative, upper
bound estimate.
For non-carcinogens, EPA uses the reference dose (RfD) as the dose response
parameter in calculating the criteria. The RfD was formerly referred to as an
"Acceptable Daily Intake" or ADI. The RfD is useful as a reference point for gauging
the potential effects of other doses. Usually, doses that are less than the RfD are not
likely to be associated with any health risks, and are therefore less likely to be of
regulatory concern. As the frequency of exposures exceeding the RfD increases and as
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the size of the excess increases, the probability increases that adverse effects may be
observed in a human population. Nonetheless, a clear conclusion cannot be
categorically drawn that all doses below the RfD are "acceptable" and that all doses in
excess of the RfD are "unacceptable."
In extrapolating non-carcinogen animal test data to humans, EPA uses an
uncertainty factor (formerly known as a safety factor). The uncertainty factor is
based upon professional judgment and ranges from 10 to 1000.
IRIS maintains files containing reference doses for chronic noncarcinogenic
health effects, and slope factors and unit risks for chronic exposures to carcinogens.
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4.0 EXPOSURE ASSESSMENT AND KEY ASSUMPTIONS
Once the hazard identification and dose-response assessment have been
completed, the next step is exposure assessment to determine safe exposure levels.
Exposure assessment is the process of characterizing the human populations exposed
to the chemicals of concern, the environmental transport and fate pathways of those
chemicals, and the frequency, magnitude, and duration of the exposure dose. In the
water quality criteria methodology, the exposure assessment includes calculation of the
ambient water concentrations which do not represent a significant risk to human
health. The exposure assessments used in calculating the criteria are limited with
respect to accounting for other sources of exposure to a pollutant. In the case of
carcinogens, exposure assessments assume that all exposure to a pollutant occurs
through ingestion of water and contaminated fish and shellfish and incremental risks
are calculated on this basis. In the case of non-carcinogens, the equation used has the
ability to include both intake from other dietary sources and intake from air.
However, if there is insufficient data for air and other dietary sources, it is assumed
that exposure is only from ingestion of water and fish.
Ideally, ambient water quality criteria should represent levels for compounds in
ambient water that do not pose a hazard to human populations. However, in any
realistic assessment of human health hazard, it is not possible to attain completely
eliminate hazards or achieve zero risk. Ideally, criteria would be based on detailed
knowledge of dose-response relationships in humans, including all sources of chemical
exposure, the types of toxic effects elicited, if any, the existence of thresholds for the
toxic effects, the significance of toxicant interactions, and the variances of sensitivities
and exposure levels within human populations. In practice, such absolute criteria
cannot be established because of deficiencies in both the available data and the means
of interpreting this information. Consequently, the human health criteria proposed for
carcinogens are designed to minimize, or at least specify the potential risk to humans
due to substances in ambient water. Human health criteria for non-carcinogens are
designed to minimize the human health hazard.
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Potential social or economic costs and benefits are not considered in the
formulation of the criteria. Also, analytical detection limits are not considered in
recommending criteria.
In the exposure assessment, information is reviewed on current levels of human
exposure to the individual pollutant from all sources. Much of the data are obtained
from monitoring studies of air, water, food, soil, and human or animal tissue residues.
The major purpose of this review is to provide background information on the
contribution of water exposure relative to all other sources.
Information on exposure can be valuable in developing and assessing a water
quality criterion. In these documents exposure from consumption of contaminated
water and contaminated fish and shellfish products is used in criterion formulation.
Data for all modes of exposure are useful in relating total intake to the expected
contribution from contaminated water, fish, and shellfish. In addition, information on
all routes of exposure, not limited to drinking water and fish and shellfish ingestion,
can be used to justify or assess the feasibility of the formulation of criteria for
ambient water.
In development of the criteria, several key assumptions are made and should be
recognized when applying the criteria to a given situation. First, the criteria are not
based on water quality monitoring data and, as noted above, the criteria represent
modeled risks, as opposed to actual risks. The target population is a national average
population. States may adjust the exposure assumptions to reflect local conditions,
although in practice this has been the exception rather than the rule.
Second, it is important to recognize that calculation of the criteria does not take
into account special groups of the population which may be more sensitive to the
effects of a particular chemical, such as pregnant women, young children, or the
elderly. Also, the calculation is explicitly done for a 70 kg adult. Nor does it take
into account groups which may receive additional exposure to the chemical from other
sources such as occupational exposure. It also does not take into account groups
which may consume large quantities of fish, such as sport fishermen.
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Third, exposure pathways considered in calculating the criteria are ingestion of
drinking water (EPA assumes 2 liters/day contaminated at the criteria concentration),
and consumption of fish (EPA assumes6.5 grams/day, contaminated at the criteria
concentration multiplied by a bioconcentration factor). The assumed water
consumption of 2 liters/day is taken from the National Academy of Sciences
publication "Drinking Water and Health" (1977). The 2 liters/day amount was also
used by EPA in calculating interim drinking water standards (NAS, 1977). This factor
may be eliminated for water which is not an actual or potential source of drinking
water. In the water quality criteria calculations, an estimated consumption of 6.5
grams/day is assumed for commercially and recreationally harvested fish and shellfish
from estuarine and fresh waters. The value of 6.5 g/day is an average per-capita
consumption rate for the U.S. population, including non-consumers (U.S. EPA, 1989).
The inclusion of non-consumers may make the number somewhat under conservative.
As these criteria must serve as national guidance, no attempt is made in the
calculation of the criteria to account for variation among individuals in the amount of
fish consumed. Also, estimates of average U.S. consumption do not account for
subpopulations in areas (such as the Great Lakes) that may consume large quantities
(e.g. 20 g/day) of locally caught sport fish.
The use of fish consumption as an exposure factor requires the quantification of
pollutant residues in the edible portions of the ingested species. Accordingly,
bioconcentration factors (BCFs) are used to relate pollutant residues in aquatic
organisms to the pollutant concentration in the ambient waters in which they reside.
Strictly speaking, the BCF is defined as the theoretical ratio between the concentration
of a chemical in a fish and the concentration of a pollutant in the surrounding water,
at fqirilihriimv Depending on the mechanisms and rates of chemical transfer (through
the gills, through ingestion, through excretion) a fish may not be at equilibrium and
therefore may exhibit a different ratio. The term bioaccumulation factor (BAF) refers
to the measured value of this ratio in a field situation. The terms are frequently used
imprecisely and misunderstandings can occur.
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One common usage is to consider the BCF only to include intake from water,
and the BAF to additionally include food input. One reason this is misleading is that
BCFs so measured are often measured for short periods of time (to preclude feeding)
and no equilibrium is reached. These BCFs are, therefore, frequently less than field
measured BAFs. However, a true BCF represents an upper limit which should not be
exceeded. Should a fish consume an amount in excess of that determined by the true
BCF, it would simply excrete the excess or actually serve as a source of the pollutant
to the water, through the gills. There have, however, been some studies which
suggest thermodynamic equilibrium may not always be present in the environment.
Three different procedures are used to estimate the BCF, depending upon the
lipid solubility of the chemical and the availability of bioconcentration data. For lipid-
soluble compounds, the average BCF is calculated from the weighted average percent
lipids in the edible portions of consumed freshwater and estuarine fish and shellfish.
This weighted average was calculated to be 3.0 percent using data on consumption of
each species and its corresponding percent lipids. Because the steady-state BCFs for
lipid-soluble compounds are proportional to percent lipids in tissues, BCFs for fish and
shellfish can be adjusted to the average percent lipids for aquatic organisms consumed
by the U.S. population. For many lipid-soluble pollutants, at least one BCF has been
determined for which the percent lipid value was measured in the exposed tissues.
With 3.0 percent as the weighted average percent lipids for freshwater and
estuarine fish and shellfish in the average diet, a BCF, and a corresponding percent
lipid value, the weighted average bioconcentration factor can be calculated. For
example, where:
Weighted average percent lipids for average diet = 3.0 %, and
Measured BCF for Trichloroethylene with bluegills at 4.8% lipids = 17
Weighted average BCF for average diet equals:
BCF = 17 x 3.0% = 10.6
4.8%
As an estimate, 10.6 is used for the BCF for the water quality criteria.
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In those cases where an appropriate bioconcentration factor is not available, the
equation "Log BCF = (0.85 Log P) - 0.70" has beeen used by EPA to estimate the BCF
for aquatic organisms containing about 7.6 percent lipids from the octanol/water
partition coefficient P. An adjustment for percent lipids in the average diet versus 7.6
percent is made in order to derive the weighted average bioconcentration factor.
There are other similar equations in general use.
For non-lipid-soluble compounds, the available BCFs for the edible portion of
consumed freshwater and estuarine fish and shellfish are weighted according to
consumption factors for these various types of fish to determine a weighted BCF
representative of the average diet.
Human body weight is assumed to be 70 kg in calculations of ambient water
quality criteria. It should be noted that this body weight is not protective of pregnant
women and children. In other risk calculations, EPA has used 50 kg to represent
pregnant women.
As noted in the previous sections on hazard identification and dose response
relationships, the existing toxicity data must be reviewed to determine the type of
effects of the chemical and the dose response relationship. If the chemical is classified
as a carcinogen, it is assumed to have no threshold, and the incremental risks of
developing cancer are calculated. If the compound is not classified as a carcinogen, it
is assumed to have a threshold below which effects will not be observed, and the
criterion is calculated based on this RfD. Examples of calculations for both a
carcinogen and a noncarcinogen are given below.
4.1 Calculation of Criteria for Non-threshold Effects (Carcinogens^
After the decision has been made that a compound has the potential for causing
cancers in humans, and that data exist which permit the derivation of a criterion, the
water concentrations which are estimated to cause a lifetime, upper bound
carcinogenic risk of 10s, 10*, and 107 are determined. The lifetime carcinogenicity
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risk is the probability that a person would get cancer sometime in his or her life
assuming continuous exposure to the compound.
The data used for quantitative estimates are of two types: (1) lifetime animal
studies, and (2) epidemiologic studies where excess cancer risk has been associated
with exposure to the agent. In animal studies it is assumed, unless evidence exists to
the contrary, that if a carcinogenic response has been documented at the dose levels
used in the study, then proportionately lower responses will also be observed at all
lower doses, with an incidence determined by a linear extrapolation model which
calculates the carcinogenic slope factor discussed in the Dose-Response Assessment
Section of this report.
An example of how criteria are calculated for carcinogens is described below.
Since carcinogens are assumed to have a nonthreshold dose/response characteristic,
there is no recognized safe concentration for a human carcinogen. Therefore, the
recommended concentration of a carcinogen in water for maximum protection of
human health is zero. Because attaining a zero concentration level may not be
feasible in some cases, and in order to assist EPA and the States in the possible future
development of water quality regulations, concentrations of the carcinogenic
compound corresponding to several incremental lifetime cancer risk levels are
estimated. A cancer risk level provides an estimate of the additional incidence of
cancer that may be expected in an exposed population. A risk of 10* for example,
indicates a probability of one additional case of cancer for every 100,000 people
exposed; a risk of 10* indicates one additional case of cancer for every million people
exposed, and so forth.
For carcinogens, the criteria calculation is as follows:
Criterion = fbody weight x risk level)
potency x (water consumption + fish consumption x BCF)
The calculations for hexachlorobutadiene (HCBD) are described here as an
example of criteria formulation for a carcinogen. HCBD is produced in the United
States as a by-product of the manufacture of chlorinated hydrocarbons such as
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tetracholoethylene, trichloroethylene, and carbon tetrachloride. It is used as a solvent
for many organic substances. HCBD has a low vapor pressure and, thus, may not
volatilize rapidly from the aqueous environment to the atmosphere. Concentrations
observed in water indicate the HCBD may be quite persistent in the environment. It
may also be adsorbed onto the sediments, particularly in areas high in organic
content.
Review of toricity literature indicates the kidney appears to be the organ most
sensitive to HCBD. The carcinogenic effects of renal tubular adenomas and
adenocarcinomas were strongly demonstrated at a dosage of 20 mg/kg/day in the diet
in rats in a two year feeding study. Incidence rates for dose levels of 0.0, 0.2, 2.0,
and 20.0 were 1/90, 0/40, 0/40, and 9/39, respectively. A q," (carcinogenic slope
factor) value of 0.07752 (mg/kg/day)'1 was calculated from the rat study data.
Bioconcentration factors are available for HCBD but the necessary data
concerning percent lipids are not. Therefore, the equation "Log BCF = (0.85 Log P) -
0.70" can be used to estimate the BCF for aquatic organisms that contain about 7.6
percent lipids from the octanol/water partition coefficient (P). Based on a measured
log P value of 1.82, the steady-state bioconcentration factor for HCBD is estimated to
be 7.03. An adjustment factor of 3.0/7.6 = 0.395 can be used to adjust the
estimated BCF from 7.6 percent lipids (on which the equation is based), to the 3.0
percent lipids, which is the weighted average for consumed fish and shellfish. Thus,
the weighted average bioconcentration factor for HCBD and the edible portion of all
freshwater and estuarine aquatic organisms consumed by the U.S. population is
calculated to be 7.03 x 0.395 = 2.78.
Parameters used in calculation of the criterion for the 10* risk level are as
follows:
Body weight = 70 kg
Risk level = lO*
Potency = 0.07752 (mg/kg/day)'1
Water consumption = 2 liters/day
Fish consumption = 6.5 grams/day = 0.0065 kg/day
Bioconcentration factor = 2.78
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17
The calculation of an ambient water quality criterion for HCBD based on fish
consumption at the 10"" risk level using the formula given above is as follows:
Criterion = (70 kg x IP"6!
0.07752 (mg/kg/day)' x (2 liters/day + 0.0065 kg/day x 2.78)
= 0.45 ug/L
The criteria for the upper bound risk levels of 10* and 107 are 4.5 ug/L and 0.045
ug/L, respectively, assuming consumption of 2 liters of drinking water and 6.5 grams
of fish and shellfish per day. Approximately one percent of the HCBD exposure
results from consumption of aquatic organisms. If the exposure is assumed to be from
fish alone, the water quality criteria associated with risk levels of 10*, 10*, and 107
are 500 ug/L, 50 ug/L, and 5.00 ug/L, respectively.
4.2 Calculation of Criteria for Threshold Effects
In developing guidelines for deriving criteria based on noncarcinogenic responses,
five types of response levels are considered:
NOEL: No-Observed-Effect Level
NOAEL: No-Observed-Adverse-Effect Level
LOEL: Lowest-Observed-Effect Level
LOAEL: Lowest-Observed-Adverse-Effect Level
PEL: Frank-Effect Level
Adverse effects are defined as any effects which result in functional impairment and/or
pathological lesions which may affect the performance of the whole organism, or
which reduce an organism's ability to respond to an additional challenge. Available
data on the five types of effects are evaluated to determine the threshold effects
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18
concentration, and to estimate an RfD. In determining an RfD, an uncertainty factor
(formerly referred to as a safety factor) ranging from 10 to 1000 is applied to the
estimated threshold level, depending on the confidence in the available data. When
the quality and quantity of experimental data are satisfactory, a low uncertainty factor
is used; when data are judged to be inadequate or equivocal, a larger uncertainty
factor is used. In other words, uncertainty factors are assigned on a case specific
basis based on somewhat subjective judgements of the quality and quantity of the
data. EPA maintains a data base on reference doses (RfDs) in the IRIS system. The
RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a
daily exposure to the human population (including sensitive subgroups) that is likely
to be without appreciable risk of deleterious effects during a lifetime. RfDs are based
on an assumption of long-term exposure and may not be appropriately applied to
short-term exposure situations.
For threshold chemicals (noncarcinogens), the criteria are based on an RfD, and
dietary and inhalation exposures are considered where data is available. The formula
is:
Criterion = RfD - (dietary intake + air intake)
(water consumption + fish consumption x BCF)
Toluene is used below as an example for calculation of criteria for a threshold
chemical. Toluene is used in the production of benzene and other chemicals as well
as being used directly in gasoline and as a solvent. Although it is volatile, it has been
detected in finished water supplies at levels ranging from 0.1 ug/L to 11 ug/L.
A number of investigations of the subacute and chronic toricity of toluene have
been conducted. Although most were inhalation studies, at least one long-term oral
dosing study was conducted in which female rats were given toluene at 118, 354, and
590 mg/kg in olive oil by stomach tube five times weekly for 193 days. No adverse
effects on growth appearance and behavior, mortality, organ/body weights, blood urea
nitrogen levels, bone marrow counts, peripheral blood counts, or morphology of major
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19
organs were observed at any dose level. The lack of toxicity reported in this study is
supported by findings of other groups of investigators who found no evidence of
residual injury in a variety of animal species subjected to toluene vapor for varying
times over periods as long as 18 months. Therefore, the highest dose utilized in the
oral study, 590 mg/kg was used as the basis for calculating the RfD for toluene.
Since no other data were available on effects at higher levels, 590 mg/kg was
assumed to be the "maximum-no-effect" dose. However, since the highest dose had no
observed effect, no information was available on the lowest observed effects. A single
oral dose of 2.4 g/kg had no hepatotoxic effects in rats and the oral LDM for toluene
in young adult rats was found to be 7.0 g/kg- It is possible that the actual
"maximum-no-effect" dose may be lower than 590 mg/kg, should alternative indices of
toxicity be evaluated. Humans may prove to be more sensitive to toluene than
experimental animals. Thus, a safety factor of 1,000 was applied. Assuming a body
weight of 70 kg and adjusting for the dosing of five times per week, the RfD is
calculated as follows:
RfD = 590 mg/kg x 70 kg x 5/7 dav = 29.5 mg/day
1,000
It is assumed that 100 percent of man's exposure comes from water. Although it
is desireable to arrive at a criterion level for water based upon total exposure
potential, the database for exposures other than water is not sufficient to allow a
factoring of air intake and dietary intake (other than fish and shellfish) into the
calculation of the criterion.
No measured steady-state bioconcentration factor (BCF) was available for
toluene. Therefore, the equation "Log BCF = (0.85 Log P) - 0.70" was used to
estimate the BCF for aquatic organisms that contain about 7.6% lipids for the octanol
water partition coefficient (P). Based on an average measured Log P value of 2.51,
the steady-state bioconcentration factor for toluene is estimated to be 27.1. An
adjustment factor of 3.0/7.6 = 0.395 can be used to adjust the estimated BCF from
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20
7.6% lipids (on which the equation is based) to 3.0% lipids, is the weighted average
for consumed fish and shellfish. Thus, the weighted average bioconcentration factor
for toluene and the edible portion of all freshwater and estuarine aquatic organisms
consumed by the U.S. population is calculated to be 27.1 x 0.395 = 10.7
Consumption of 2 liters of water daily and 6.5 g of contaminated fish having a
bioconcentration factor of 10.7, would result in, assuming 100% gastrointestinal
absorption of toluene, a maximum permissible concentration of 14.3 mg/L for the
ingested water:
Criterion = 29.5 mg/dav = 14.3 mg/L
2 L + (10.7 x 0.0065)
Drinking water contributes 97% of the assumed exposure, while eating contaminated
fish products accounts for 3%. The criterion level for toluene can alternatively be
expressed as 424 mg/L if exposure is assumed to be from the consumption of fish and
shellfish products alone.
The principal goal of the water quality criteria program is to provide guidance
for maintaining acceptable water quality under a program for source reduction. The
development of an acceptable level for fish tissue is not a goal of the water quality
criteria methodology, and the SAB did not review the methodology for this use.
However, by taking the criteria and multiplying by the BCF factor used in its
derivation, an implicit fish tissue level may be calculated. This could then be used to
establish a fish contamination advisory, if measured fish levels exceed this level. This
calculation is the same for carcinogens and non-carcinogens. For example, using the
criterion for toluene, the acceptable fish tissue level would be calculated as follows:
Acceptable fish tissue level = Criterion x BCF = 14.3 ppm x 10.7 = 153 ppm
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21
5.0 RISK MANAGEMENT DECISION
Water quality criteria for the protection of human health are issued as guidance
for making risk management decisions. These criteria present scientific data and
guidance on the environmental effects of pollutants which can be used to derive
regulatory requirements for water quality, such as State water quality standards. The
criteria are EPA's recommended ambient water concentrations which EPA believes do
not represent a significant risk to human health. States are free to make risk level
determinations as part of their risk management process.
The water quality criteria methodology is purely a risk assessment as opposed to
a risk management process. No benefits analysis is considered, nor are costs. The
differences between carcinogens and non-carcinogens involve the dose-response factors
described above. For non-carcinogens, the risk assessment leads to a one value
criterion. For carcinogens, the assessment leads to a series of criteria associated with
incremental increases in the risk of developing cancer. The criteria are calculated for
individual chemicals with no consideration of additive, synergistic, or antagonistic
effects in mixtures.
Also, the criteria do not take into account special populations which may be at
additional risk, such as sport fisherman or regional populations who consume
quantities of fish much higher than the national average. If the conditions within a
State differ from the assumptions made in calculation of the criteria, the States have
the options to perform their own risk assessments and to set standards which more
accurately reflect their specific conditions and which provide adequate protection for
human health.
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22
6.0 REFERENCES
40 Code of Federal Regulations (CFR), Part 136, "Guidelines Establishing Test
Procedures for the Analysis of Pollutants Under the Clean Water Act". (49
Federal Register 2, October 26, 1984).
45 Federal Register 79347, "Water Quality Criteria Documents; Availability,
Appendix C - Guidelines and Methodology Used in the Preparation of Health
Effect Assessment Chapters of the Consent Decree Water Criteria Documents"
November 28, 1980.
National Academy of Sciences (NAS), 1977. "Drinking Water and Health".
U.S. Environmental Protection Agency (U.S. EPA), 1989. "Assessing Human
Health Risks from Chemically Contaminated Fish and Shellfish: A Guidance
Manual". EPA-503/8-89-002. September.
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APPENDIX A
WATER QUALITY CRITERIA DOCUMENTS; AVAILABILITY
(45 Federal Register 79318)
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Friday
November 28, 1980
Part V
Environmental
Protection Agency
Water Quality Criteria Documents;
Availability
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79318
Federal Register / Vol. 45, No. 231 / Friday, November 28,1080 / Notices
ENVIRONMENTAL PROTECTION
AGENCY
IFRL 1623-3]
Water Quality Criteria Documents;
Availability
AGENCY: Environmental Protection
Agency.
ACTION; Notice of Water Quality Criteria
Documents. . =
SUMMARY: EPA announces the
availability and provides summaries of
water quality criteria documents for 84
toxic pollutants or pollutant categories.
These criteria are published pursuant to
section 304(a)(l) of the Clean Water Act
AVAILABILITY OP DOCUMENTS:
Summaries of both aquatic-based and
health-based criteria from the
documents are published below. Copies
of the complete documents for
individual pollutants may be obtained
from the National Technical Information
Service (NTIS), 5285 Port Royal Road.
Springfield. VA 22161, (703-487-4650). A
list of the NTIS publication order
numbers for all 64 criteria documents is
published below. These documents are
also available for public inspection and
copying during normal business hours
at: Public Information Reference Unit,
U.S. Environmental Protection Agency,
Room 2404 (rear], 401M St, S.W.,
Washington, D.C. 20460. As provided La
40 CFR Part 2, a reasonable fee may be
charged for copying services. Copies of
these documents are also available for
review in the EPA Regional Office
libraries.
Copies of the documents are not
available from the EPA office listed
below. Requests sent to that office will
be forwarded to NTIS or returned to the
sender. . •
1. Acenaphthene. PB81-117269. -
2. Acroleln, PB81-117277.
3. Acrylonltrile, PB81-117285.
4. Aldrin/Dieldrin, PB81-117301.
5. Antimony, PB81-117319.
6. Arsenic, PB81-117327.
7. Asbestos. PB81-117335.
a. Benzene, PB81-117293.
8. Benzldlne, PB81-117343.
10. Beryllium, PB81-117350.
11. Cadmium, PB81-117368.
12. Carbon Tetrachloride, PB81-
117376,
13. Chlordane, PB81-117384.
14. Chlorinated benzenes, PB81-
117392.
15. Chlorinated ethanes. PB81-117400.
16. Chloroalkyl ethers, PB81-117418.
17. Chlorinated naphthalene, PB81-
117426.
18. Chlorinated phenols, PB81-117434.
18. Chloroform, PB81-117442.
20.2-chlorophenol, PB81-1174S9,
21. Chromium, PB81-117467.
22. Copper. PB81-117475.
23. Cyanides, PB81-117483.
24. DDT, PB81-117491.
25. Dichlorobenzenes. PB81-117509.
26. Dlchlorobenzidine, PB81-117517.
27. Dichloroethylenes. PBB1-117525.
28. 2,4-dlchlorophenol, PB81-117533.
29. Dichloropropanes/propenes, PB01-
117541.
30.2,4-dimethylphahol, PBB1-117558,
• 31. Dlnltrotoluene, PB81-117S6&
32. Diphenylhydrazine, PB81-117731.
33. Endosulfan. PB81-117574.
34. Endrln, PB81-117582.
35. Ethylbenzene, PB81-117890.
36. Fluoranthene, PB81-117608.
37. Haloethers. PB81-117616.
38. Halomethanes, PB81-117624.
39. Heptachlor, PB81-117832.
4a Hexachlorobutadiene, PB81-
117640.
41. Hexachlorocyclohexane, PB81-
1176B7.
42, Hexachlorocyclopentadlene. PB81-
117665.
43. Isophorone, PB81-117873.
44. Lead, PB81-117681.
45. Mercury, PB81-117699.
48. Naphthalene. PB81-117707.
47. Nickel, TB81-117715.
48. Nitrobenzene, PB81-117723.
49. Nitrophenols, PB81-117749.
50. Nitfosamines, PBB1-117758.
51. Pentachlorophenol, PB81-117704.
52. Phenol PB81-117772. '
53. Phthalate esters. PB81-117780.
54. Polychlorinated biphenyls (PCBs),
PBai-117788.
55. Polynuclear aromatic
hydrocarbons, PB81-11780B.
56. Selenium, PB81-117814.
57. Silver, PB81-117822.
58. Tetrachloroethylene. PB81-117830.
59. Thallium, PB81-117848.
60. Toluene, PB81-117855.
61. Toxaphene. PB81-117863.
62. Trichloroethylene, PB81-117871.
63. Vinyl chloride, PB81-117889.
64. Zinc. PB81-117897.
FOR FURTHER INFORMATION CONTACT:
Dr. Frank Gostomskl, Criteria and
Standards Division (WH-585), United
States Environmental Protection
Agency, 401M Street, S.W.,
Washington, D.C. 20460, [202] 245-3042.
SUPPLEMENTARY INFORMATION:
Background
Pursuant to section 304[a)[l) of the
Clean Water Act. 33 U.S.C. 1314(a)(l),
EPA is required to periodically review
and publish criteria for water quality
accurately reflecting the latest scientific
knowledge:
(A) on the kind and extent of all
identifiable affects on health and welfare
including, but not limited to, plankton, fish,
shellfish, wlldllfa, plant life, shorelines.
beaches, esthetics, and recreation which may
be expected from the presence of pollutants
in any body of water, Including ground water.
(B) on the concentration and dispersal of
pollutants, or their byproducts, through
biological, physical, and'chemical processes.
and (C) on the effects of pollutants on
biological community diversity, productivity,
and stability, including information on the
factors affecting rates of eutrophicalion and
rates of organic a nd' inorganic sedimentation
for varying types of receiving waters.' •
EPA is today announcing the
availability of criteria documents for 64
of the 65 pollutants designated as toxic
under section 307(a)(l) of the Act The
document on TCDD (Dioxin) will be
published within the next month after
review of recent studies. Criteria for the
section 307(a)(l) toxic pollutants being
published today will replace the criteria
for those same pollutants found in the
EPA publication. Quality Criteria far
Water, (the "Red Book.") Criteria for all
other pollutants and,water constituents
found in the "Red Book" remain valid.
The criteria published today have been
derived using revised methodologies for
determining pollutant concentrations
that will, when not exceeded,
reasonably protect human health and
aquatic life. Draft criteria documents
were made available for public
comment (44 FR15926, March 15,1979,
44 FR 43660, July 25,1879, 44 FR 56628,
October 1,1978). These final criteria-
have been derived after consideration of
all comments received.
These criteria documents are also
issued in satisfaction of die Settlement
Agreement in Natural Resources
Defense Council, et al. v. Train 8 EJtC.
2120 (1976). modified, 12 E.R.C. 1833
(D.D.C. 1979). Pursuant to paragraph 11
of that agreement EPA is required to
publish criteria documents for the 65
pollutants which Congress, in the 1977
amendments to the Act, designated as
toxic under section 307(a)(l). These
documents contain recommended
maximum permissible pollutant
concentrations consistent with the
protection of aquatic organisms, human
health, and some recreational activities.
Although paragraph 11 Imposes certain
obligations on the Agency, it does not
create additional authority.
The Development of Water Quality
Criteria
. Section 304(a)[l) criteria contain two
essential types of information: (1)
discussions of available scientific data
on the effects of pollutants on public
health and welfare, aquatic life and
recreation, and [2] quantitative
concentrations or qualitative
assessments of the pollutants in water
which will generally ensure water
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Federal Register / Vol. 45. No.. 231_ / Friday. November 28, 1980 / Notices
79319
quality adequate to support a specified
water use. Under section 304(a)(l), these
criteria are based solely on data and
scientific judgments on the relationship
between pollutant concentrations and
environmental and human health
effects. Criteria values do not reflect
considerations of economic or
technological feasibility.
Publication of water quality criteria of
this type has been an ongoing process
which EPA, and its predecessor Agency.
tJle.Federal Water Pollution Control
Administration, have been engaged in
since 1968. At that time the first Federal
compilation of water quality criteria, the
so-called "Green Book" (Water Quality
Criteria), was published. As now, these
criteria contained both narrative
discussions of the environmental effects
of pollutants on a range of possible uses
and concentrations of pollutants
necessary to support these uses. Since
that time, water quality criteria have
been revised and expanded with
publication of the "Blue Book" (Water
Quality Criteria1972) in 1973 and the
"Red Book" (Quality Criteria for Water)
in 1976.
Since publication of the Red Book
there have been substantial changes in
EPA*s approach to assessing scientific
data and deriving section 304(a)[l]
criteria. Previous criteria were derived
from a limit edtlata base. For many
pollutants, an aquatic life criterion was
derived by multiplying the lowest
concentration known to have acute
lethal effect on half of a test group of an
aquatic species (the LC50 value) by an
application factor in order to protect
against chronic effects. If data showed a
substance to be bioaccumulative or to
have other significant long-term effects,
a factor was used to reduce the
indicated concentrations to a level
presumed to be protective. Criteria for
the protection of human health were
similarly derived by considering the
pollutants' acute, chronic, and
bioaccumulative effects on non-human
mammals and humans.
Although a continuation of the
process of criteria development, the
criteria published today were derived
using revised methodologies
(Guidelines) for calculating the Impact
of pollutants on human health and
aquatic organisms. These Guidelines
consist of systematic methods for
assessing valid and appropriate data
concerning acute and chronic adverse
effects of pollutants on aquatic
organisms, non-human mammals, and
humans. By use of these data in
prescribed ways, criteria are formulated
to protect aquatic life and human health
from exposure to the pollutants. For
some pollutants, bioconcentration
properties are used to formulate criteria
protective of aquatic life uses. For
almost all of the pollutants,
bioconcentration properties are used to
assess the relative extent of human
exposure to the pollutant either directly
through ingestion of water or indirectly
through consumption of aquatic
organisms. Human health criteria for
carcinogens are presented as
incremental risks to man associated .
with specific concentrations of the
pollutant in ambient water. The
Guidelines used to derive criteria
protective of aquatic life and human
health are fully described in appendices
B and C, respectively, of this Notice.
The Agency believes that these
Guidelines provide criteria which more
accurately reflect the effects of these
pollutants on human health and on
aquatic organisms and their uses. They
are based on a more rational and
consistent approach for using scientific
data. These Guidelines were developed
by EPA scientists in consultation with
scientists from outside the Agency and
they have been subjected to intensive
public comment.
Neither the Guidelines nor the criteria
are considered inflexible doctrine. Even
at this time. EPA is taking action to
employ the resources of peer review
groups, including the Science Advisory
Board, to evaluate recently published
data, and EPA is conducting its own
evaluation of new data to determine
whether revisions to the criteria
documents would be warranted.
The criteria published today are
based solely on the effect of a single
pollutant. However, pollutants in
combination may have different effects
because of synergistic, additive, or
antagonistic properties. It is impossible
in these documents to quantify the
combined effects of these pollutants.
and persons using criteria should be
aware that site-specific analysis of
actual combinations of pollutants may
be necessary to give more precise
indications of the actual environmental
impacts of a discharge.
Relationship of the Section 304(a)(l) .
Criteria to Regulatory Programs
Section 304(a)(l) criteria are not rules
and they have no regulatory inpact.
Rather, these criteria present scientific
data and guidance on the ehviromental
effect of pollutants which can be useful
to derive regulatory requirements based
on considerations of water quality
impacts. Under the Clean Water Act,
these regulatory requirements may
include the promulgation of water
quality-based effluent limitations under
section 302, water quality standards
under section 303, or toxic pollutant
effluent standards under section 307.
States are encouraged to begin to
modify or, if necessary, develop new
programs necessary to support the
implementation of regulatory controls
for toxic pollutants. As appropriate,
States may incorporate criteria for toxic
pollutants, based on this guidance, into
their water quality standards.
Section. 304(a)(l) criteria have been
most closely associated with the
development of State water quality
standards/and the "Red Book" values
have; in the past, been the basis for
EPA's assessments of the adequacy of
State requirements. However, EPA is
now completing a major review of its
water quality standards policies and
regulations. After consideration of
comments received on an Advance
Notice of Proposed Rulemaking (43 FR
29588. July 10,1978) and the draft
criteria documents, the Agency intends
to propose, by the end of this year, a
revised water quality standards
regulation which will clarify the
Agency's position on a number of
significant standards issues.
With the publication of these criteria.
however, it is. appropriate to discuss
EPA's current thinking on standards
issues relating to their use. This
discussion does not establish new
regulatory requirements and is intended
as guidance on the possible uses of
these criteria and an indication of future
rulemaldng the Agency, may undertake.
No substantive requirements will be
established without further opportunity
for public comment.
Water Quality Standards
Section 303 of the Clean Water Act
provides that water quality standards be
developed for all surface waters. A
water quality standard consists
basically of two parts:' (1) A "designated
use" for which the water body is to be
protected (such as "agricultural,"
"recreation" or "fish and wildlife"), and
(2) "criteria" which are numerical
pollutant concentration limits or
narrative statements necessary to
preserve or achieve the designated use.
A water quality standard is developed
through State or Federal rulemaking
proceedings and must be translated into
enforceable effluent limitations in a
point source (NPDES) permit or may
form the basis of best management
practices applicable to nonpoint sources
under section 208 of the Act.
Relationship of Section W4(a)(l)
Criteria to the Criteria Component of
State Water Quality Standards:
In the ANPRM, EPA announced a
policy of "presumptive applicability" for
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79320
Federal Register / Vol. 45, No. 231 / Friday, November 28, 1980 / Notices
section 304(a](l) criteria codified in the
"Red Book." Presumptive applicability
meant that a State had to adopt a
criterion for a particular water quality
parameter at least as stringent as the
recommendation in the Red Book unless
the State was able to justify a less
stringent criterion based on: natural
background conditions, more recent
scientific evidence, or local, site-specific
information. EPA Is rescinding the
policy of presumptive applicability
because it has proven to be too
inflexible in actual practice.
Although (he section 304(a)(l) criteria
represent a reasonable estimate of
pollutant concentrations consistent with
the maintenance of designated water
uses, States may appropriately modify
these values to reflect local conditions.
In certain circumstances, the criteria
may not accurately reflect the toxicity of
a pollutant because of the effect of local
water quality characteristics or varying
sensitivities of local populations. For
example, in some cases, ecosystem
adaptation may enable a viable,
balanced aquatic population to exist in
waters with high natural background
levels of certain pollutants. Similarly,
certain compounds may be more or less
toxic in some waters because of
differences in alkalinity, temperature,
hardness, and other factors.
Methods for adjusting the section
304(a)(l) criteria to reflect these local
differences are discussed below.
Relationship of Section 304(a)(l)
Criteria to Designated Water Uses:
The criteria published today can be
used to support the designated uses
which are generally found in State
standards. The following section
discusses the relationship between the
criteria and Individual use"
classifications. Where a water body is
designated for more than one use, -
criteria necessary to protect the most
sensitive use should be applied.
1. Recreation: Recreational uses of
water include such activities as
swimming, wading, boating and fishing.
Although insufficient data exist on the
effects of toxic pollutants resulting from
exposure through such primary, contact
as swimming, section 304(a)(l) criteria
based on human health effects may be
used to support this designated use
where fishing is included in the State
definition of "recreation." In this
situation only the portion of the criterion
based on fish consumption should be
used.
2. Protection and Propagation of Fish
and Other Aquatic Life: The section
304(a)(l) criteria based on toxicity to
aquatic life may be used directly to
support this designated use.
3. Agricultural and Industrial Uses:
The section 304(a)(l) criteria were not
specifically developed to reflect the
impact of pollutants on agricultural and
industrial uses. However, the criteria
developed for human health and aquatic
life are sufficiently stringent to protect
these other uses. States may establish
criteria specifically designed to protect
these uses.
. 4. Public, Water Supply: The drinking
" water exposure component of the
human health effects criteria can apply
directly to this use classification or may
be appropriately modified depending
upon whether the specific water supply
system falls within the auspices of the
Safe Drinking Water Act's (SDWA)
regulatory control, and the type and
level of treatment imposed upon the
supply before delivery to the consumer.
The SDWA controls the presence of
toxic pollutants in finished ("end-of-
tap") drinking water. A brief description
of relevant sections of this Act is
necessary to explain how the SDWA
will work in conjunction with section
304(a)(l) criteria in protecting human
health from the effects of toxics due to
consumption of water.
Pursuant to section 1412 of the SDWA,
EPA has promulgated "National Interim
Primary Drinking Water Standards" for
certain organic and inorganic
substances. These standards establish
"maximum contaminant levels"
("MCLs") which specify the maximum
permissible level of a contaminant in
water which may be delivered to a user
of a public water system now defined as
serving a minimum of 25 people. MCLs
are established based on consideration
of a range of factors Including not only
the health effects of the contaminants
but also technological and economic -•
feasibility of the contaminants' removal
from the supply. EPA is required to
establish revised primary drinking water
regulations based on the effects of a
contaminant on human health, and
include treatment capability, monitoring
availability, and costs. Under Section
1401(l)(D)(i] of the SDWA. EPA is also
allowed to establish the minimum
quality criteria for water which may be
taken into a public water supply system.
Section 304(a)(l) criteria provide
estimates of pollutant concentrations
protective of human health, but do not
consider treatment technology, costs
and other feasibility factdrs. The section
304(a)(l] criteria also include fish
bioaccumulation and consumption
factors in addition to direct human
drinking water intake. These numbers
were not developed to serve as "end of
tap" drinking water standards, and they
have no regulatory significance under
the SDWA. Drinking water standards
are established based on considerations
including technological and economic
feasibility, not relevant to section
304(a)(l) criteria. Section 304(a](i)
criteria may be analogous to the
recommended maximum contaminant
levels (RMCLs) under section
1412(b)(l)(B) of the SDWA in which,
based upon a report from the National
Academy of Sciences, the Administrator
should set target levels for contaminants
in drinking water at which "no known or
anticipated adverse effects occur and
which allows an adequate margin of
safety". RMCLs do not take treatment.
cost, and other feasibility factors into
consideration. Section 304(a)(l) criteria
are, in concept, related to the health-
based goals specified in the RMCLs.
Specific mandates of the SDWA such as
the consideration of multi-media
exposure, as well as different methods
for setting maximum contaminant levels
under the two Acts, may result in
differences between the two numbers.
MCLs of the SDWA, where they exist,
control toxic chemicals in finished
drinking water. However, because of
variations In treatment and the fact that
only a relatively small number of MCLs
have been developed, ambient water
criteria may be used by the States as a
supplement to SDWA regulations. States
will have the option of applying MCLs;
section 304(a)(l) human health effects^
criteria, modified section 304(a)(l)
criteria or controls more stringent than
these three to protect against the effects
of toxic pollutants by Ingestion from
drinking water.
For untreated drinking water supplies.
States may control toxics In the ambient
water through either use of MCLs (if
they exist for the pollutants of concern),
section 304(a)(l) human health effects
criteria, or a more strigent contaminant
level than the former two options.
For treated drinking water supplies
serving less than 25 people, States may
choose toxics control through
application of MCLs (if they exist for the
pollutants of concern and are attainable
by the type of treatment) in the finished
drinking water. States also have the
options to control toxics in the ambient
water by choosing section 304(a)(l.)
criteria, adjusted section 304(a)(l)
criteria resulting from the reduction of
the direct drinking water exposure
component in the criteria calculation to
the extent that the treatment procedure .
reduces the level of pollutants, or a more
stringent contaminant level than the
former three options.
For treated drinking water supplies
serving 25 people or greater. States must
control toxics down to levels at least as
stringent as MCLs (where they exist for
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Federal Register / Vol. 4S. No. 231 / Friday. November 2B. 1980 / Notices 79321
the pollutants of concern] In the finished
drinking water. However, States also
have the options to control toxics in the
ambient water by choosing section
304(a)(l) criteria, adjusted section
304(a}(l) criteria resulting from the
reduction of the direct drinking water
exposure component in the criteria
calculation to the extent that the
treatment process reduces the level of
pollutants, or a more stringent
contaminant level-than the former three
options.
Inclusion of Specific Pollutants in State
Standards: •
To date, EPA has not required that a
State address any specific pollutant in
its standards. Although all States have
established standards for most
conventional pollutants, the treatment of
toxic pollutants has been much less
extensive. In the ANPRM, EPA
suggested a policy under which States
would be required to address a set of
pollutants and incorporate specific toxic
pollutant criteria into water quality
standards. If. the State failed to
incorporate these criteria, EPA would
promulgate the standards based upon
these criteria pursuant to section
303Cc)(4JfB}.
In the forthcoming proposed revision
to the water quality standard
regulations, a significant change in
policy will be proposed relating to the
incorporation of certain pollutants in
State water quality standards. This
proposal will differ from the proposal
made in the ANPRM. The ANPRM
proposed an EPA-published list of
pollutants for which States would have
had to develop water quality standards.
This list might have contained some (or
all) of the 6! toxic pollutants. However,
the revised water quality standards
regulation will propose a process by
which EPA will assist States in
identifying specific toxic pollutants
required for assessment for possible
inclusion in State water quality
standards. For these pollutants, States
will have the option of adopting the
published criteria or of adjusting those
criteria based on site-specific analysis.
These pollutants would generally
represent the greatest threat to
sustaining a healthy, balanced
ecosystem in water bodies or to human
health due to exposure directly or
indirectly from water. EPA is currently
developing a process to determine
which pollutants a State must assess for
possible inclusion in its water quality
standards. Relevant factors might
include the toxicily of the pollutant, the
frequency and concentration of its
discharge, its geographical distribution,
he breadth of data underlying the
scientific assessment of its aquatic life
and human health effects, and the
technological and economic capacity to
control the discharge of the pollutant.
For some of the pollutants, all States
may be required to assess them for
possible inclusion in their standards. For
others, assessment would be restricted
to States cr limited to specific water
bodies where the pollutants pose a
particular site-specific problem.
Criteria Modification Process •
Flexibility la available in the
application of these and any other valid
water quality criteria to regulatory
programs. Although in some cases they
may be used by the States as developed,
the criteria may be modified to refect
local environmental conditions and
human exposure patterns before
Incorporation into programs such as
water quality standards. If significant
impacts of site-specific water quality
conditions in the toxicities of pollutants
can be demonstrated or significantly
different exposure patterns of these
pollutants to humans can be shown,
section 2Q4(a)(l) criteria may be
modified to reflect these local
conditions. The term "local" may refer
to any appropriate geographic area
where common aquatic environmental
conditions or exposure patterns exist.
Thus, "local" may signify a Statewide,
regional, river reach, or entire river
basin area. On the other hand, the
criteria of some pollutants might be
applicable nationwide without the need
for adaptation to reflect local
conditions. The degree of toxicity
toward aquatic organisms and humans
characteristic of these pollutants would
not change significantly due to local
water quality conditions,
EPA is examining a series of
environmental factors or water quality
parameters which might realistically be
expected to affect the laboratory-
derived water quality criterion
recommendation for a specific pollutant.
Factors such as hardness, pH,
Suspended solids, types of aquatic
organisms present, etc. could impact on
the chemical's effect in the aquatic
environment. Therefore, local
information can be assembled and
analyzed to adjust the criterion
recommendation if necessary.
The Guidelines for deriving criteria for
the protection of aquatic life suggest
several approaches for modifying the
criteria. First, toxicity data, both acute
and chronic, for local species could be
substituted for some or all of the species
used in deriving criteria for the water
quality standard. The minimum data
requirements should still be fulfilled in
calculating a revised criterion. Second,
criteria may be specifically tailored to a
local water body by use of data from
toxicity tests performed with that
ambient water. A procedure such as this
would account for local environmental
conditions in formulating a criterion
relevant to the local water body. Third,
site-specific water quality
characteristics resulting in either
enhancement or mitigation of aquatic
life toxicity for the pollutant could be
.• factored into- final formulation of the •
criterion. Finally, the criteria may be
made more stringent to ensure
protection of an individual species not
otherwise adequately protected by any
of the three modification procedures
previously mentioned.
EPA does not intend to have States
assess every local stream segment and
lake in the country on an individual
basis before determining if an
adjustment is necessary. Rather, it is
envisioned that water bodies having
similar hydrological, chemical, physical,
and biological properties will be
grouped for the purpose of criteria
adjustment. The purpose of this effort is
to assist States in adapting the section
304(a) criteria to local conditions where
needed, thereby precluding the setting of
arbitrary and perhaps unnecessarily
stringent or underprotective criteria in a
water body. In all cases, EPA will still
be required, pursuant to section 303(c),
to determine whether the State water
quality standards are consistent with
the goals of the Act, including a
determination of whether State-
established criteria are adequate to
support a designated use.
Criteria for the Protection of Aquatic
Ofe
Interpretation of the Criteria
The aquatic life criteria issued today
are summarized In Appendix A of this
Federal Register notice. Criteria have
been formulated by applying a set of
Guidelines to a data base for each
pollutant The criteria for the protection
of aquatic life specify pollutant
concentrations which, if not exceeded,
should protect most, but not necessarily -
all, aquatic life and its uses. The
Guidelines specify that criteria should
be based on an array of data from
organisms, both plant and animal,
occupying various trophic levels. Based
on these data, criteria can be derived
which should be adequate to protect the
types of organisms necessary to support
an aquatic community.
The Guidelines are not designed to
derive criteria which will protect all life
stages of all species under all
conditions. Generally some life stage of
one or more tested species, and
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
probably some untested species, will
have sensitivities below the maximum
value or the 24-hour average under some
conditions and would be adversely
affected if the highest allowable
pollutant concentrations and the worst
conditions existed for a long time. In
actual practice, such a situation is not
likely to occur and thus the aquatic
community as a whole will normally be
protected if the criteria are not
exceeded.'In any aquatic community
there is 8 wide range of Individual
species sensitivities to the effects of
toxic pollutants, A criterion adequate to
protect the most susceptible life stage of
the most sensitive species would in
many cases be more stringent than
necessary to protect the overall aquatic
community.
The aquatic life criteria specify both
maximum and 24-hour average values.
The combination of the two values is
designed to provide adequate protection
of aquatic life and its uses from acute
and chronic toxicity and
bioconcentratlon without being as
restrictive as a one-number criterion
would have to be to provide the same
amount of protection, A time period of
24 hours was chosen in order to ensure
that concentrations not reach harmful
levels for unacceptably long periods.
Averaging for longer periods, such as a
week or a month for example, could
permit high concentrations to persist •
long enough to produce significant
adverse effects. A 24-hour period was
chosen instead of a slightly longer or
shorter period in recognition of daily
fluctuations in waste discharges and of
the influence of daily cycles of sunlight
and darkness and temperature on both
pollutants and aquatic organisms.
The maximum value, which is derived
From acute toxicity data, prevents
significant risk of adverse impact to
organisms exposed to concentrations
above the 24-hour average. Merely
specifying the average value over a '
specified time period is insufficient
because concentrations of chemicals
higher than the average value can kill or
cause irreparable damage in short
periods. Furthermore, for some
chemicals the effect of intermittent high
exposures is cumulative, It is therefore
necessary to place an upper limit on
pollutant concentrations to which
aquatic organisms might be exposed.
The two-number criterion is intended to
describe the highest average ambient
water concentration which will produce
a water quality generally suited to the
maintenance of aquatic life while
restricting the extent and duration of the
excursions over that average to levels
which will not cause harm. The only
way to assure the same degree of
protection with a one-number criterion
would be to use the 24-hour average as a
concentration that is not to be exceeded
at any time in any place.
Since some substances may be more
toxic in freshwater than in saltwater, or
vice versa, provision is made for
deriving separate water quality criteria
for freshwater and for saltwater for each
substance. However, for .some
substances sufficient data may not be
available to derive one or both of these
criteria using the Guidelines.
Specific aquatic life criteria have not
been developed for all of the 65 toxic
pollutants. In those cases where there
were insufficient data to allow the
derivation of a criterion, narrative
descriptions of apparent threshold levels
for acute and/or chronic effects based
on the available data are presented.
These descriptions are intended to
convey a sense of the degree of toxicity
of the pollutant in the absence of a
criterion recommendation.
Summary of the Aquatic Life Guidelines
The Guidelines for Deriving Water
Quality Criteria for the Protection of
Aquatic Life ana its Uses were
developed to describe an objective,
internally consistent, and appropriate
way of ensuring that water quality
criteria for aquatic life would provide,
on the average, a reasonable amount of
protection without an unreasonable
amount of overprotection or
underprotection. The resulting criteria
are not intended to provide 100 percent
protection of all species and all uses of
aquatic life all of the time, but they are
intended to protect most species in a
balanced, healthy aquatic community.
The Guidelines are published as
Appendix B of this Notice. Responses to
public comments on these Guidelines
are attached as Appendix 0.
Minimum data requirements are
identified in four areas: acute toxicity to
animals (eight data points), chronic
toxicity to animals (three data points).
toxicity to plants, and residues.
Guidance is also given for discarding
poor quality data.
Data on acute toxicity are needed for
a variety of fish and invertebrate
species and are used to derive a Final
Acute Value. By taking into account the
number and relative sensitivities of the
tested species, the Final Acute Value is
designed to protect most, but not
necessarily all, of the tested and
untested species.
" Data on chronic toxicity to animals
can be used to derive a Final Chronic
Value by two different means. If chronic
values are available for a specified
number and array of species, a final
chronic value can be calculated directly.
If not, an acute-chronic ratio is derived
and then used with the Final Acute
Value to obtain the Final Chronic Value
The Final Plant Value is obtained by
selecting the lowest plant toxicity value
based on measured concentrations.
The Final Residue Value is intended
to protect wildlife which consume
aquatic organisms and the marketability
of aquatic organisms. Protection of. the •
marketability of aquatic organisms is, in
actuality, protection of a use of that
water body ("commercial fishery"). Two
kinds of data are necessary to calculate
the Final Residue Value: a
bioconcentration factor (BCF) and a
maximum permissible tissue
concentration, which can be an FDA
action level or can be the result of a
chronic wildlife feeding study. For lipid
soluble pollutants, the BCF is
normalized for percent Upids and then
the Final Residue Value is calculated by
dividing the maximum permissible
tissue concentration by the normalized
BCF and by an appropriate percent lipid
value, BCFs are normalized for percent
lipids since the BCF measured for any
individual aquatic species is generally
proportional to the percent lipids in that
species.
If sufficient data are available to
demonstrate that one or more of the
final values should be related to a water
quality characteristic, such as salinity,
hardness, or suspended solids, the final
value(s) are expressed as a function of
that characteristic.
After the four final values (Final
Acute Value, Final Chronic Value. Final
Plant Value, and Final Residue Value)
have been obtained, the criterion is
established with the Final Acute Value
becoming the maximum value and the
lowest oft he other three values .
becoming the 24-hour average value. All
of the data used to calculate the four
final values and any additional pertinent
information are then reviewed to
determine if the criterion is reasonable.
If sound scientific evidence indicates
that the criterion should be raised or
lowered, appropriate changes are made
as necessary.
The present Guidelines have been
revised from the earlier published
versions (43 FR 21B08, May 18,1978; 43
FR 28028, July 8,1878; 44 FR 1S926,
March 15,1979). Details have been
added in many places and the concept
of a minimum data base has been
incorporated. In addition, three
adjustment factors and the species
sensitivity factor have been deleted.
These modifications were the result of
the Agency's analysis of public
comments and comments received from
the Science Advisory Board on earlier
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versions of the Guidelines. These
comments and the Resultant
modifications are addressed fully in
Appendix D to this notice.
Criteria for the Protection of Human
Health
Intespretation of the Human Health
Criteria ,
The human health criteria issued
today are summarized in Appendix A of
. this Federal Register notice. Criteria for
the protection of human Health are
presented for 62 of the 85 pollutants
based on their carcinogenic, toxic, or
organoleptic (taste and odor) properties.
The meanings and practical uses of the
criteria values are distinctly different
depending on the properties on which
they are based.
The objective of the health
assessment portions of the criteria
documents is to estimate ambient water
concentrations which, in the case of
non-carcinogens, prevent adverse health
effects in humans, and in the case of
suspect or proven carcinogens, represent
various levels of incremental cancer
risk.
Health assessments typically contain
discussions of four elements: Exposure,
phannacokinetics, toxic effects, and
criterion formulation.
The exposure section summarizes
information on exposure routes:
ingestion directly from water, indirectly
from consumption of aquatic organisms
found in ambient water, other dietary
sources, inhalation, and dermal, contact.
Exposure assumptions are used to
derive human health criteria. Most
criteria are based solely on exposure
from consumption of water containing a
specified concentration of a toxic
pollutant and through consumption of
aquatic organisms which are assumed to
have bioconcentrated pollutants from
the water in which they live. Other
multimedia routes of exposure such as
air, non-aquatic diet, or dermal are not
factored into the criterion formulation
for the vast majority of pollutants due to
lack of data. The criteria are calculated
using the combined aquatic exposure
pathway and also using the aquatic
organism ingestion exposure route
alone. In criteria reflecting both the
water consumption and aquatic
organism ingestlon routes of exposure,
the relative exposure contribution varies
with the propensity of a pollutant to
hue-concentrate, with the consumption of
aquatic organisms becoming more
important as the bioconcentration factor
(BCF) increases. As additional
information on total exposure is
assembled for pollutants for which
criteria reflect only the two specified
aquatic exposure routes, adjustments in
water concentration values may be
made. The Agency intends to publish
guidance which will permit the States to
identify significantly different exposure
patterns for their populations. If
warranted by the demonstration of
significantly different exposure patterns,
this will become an element of a process
to adapt/modify human health-based
criteria to local conditions, somewhat '
analogous to the aquatic life criteria •
modification process discussed
previously. It is anticipated that States
at their discretion will be able to set
appropriate human health criteria based
on this process.
The phannacokinetics section reviews
data on absorption, distribution,
metabolism, and excretion to assess the
biochemical fate of the compounds in
the human and animal system. The toxic
effects section reviews data on acute,
subacute. and chronic toxicity,
synergistic and antagonistic effects, and
specific information on mutagenicity,
teratogenicity. and carcinogenicity.
From this review, the toxic effect to be
protected against is identified taking
into account the quality, quantity, and
weight of evidence characteristic of the
data. The criterion formulation section
reviews the highlights of the text and
specifies a rationale for criterion
development and the mathematical
derivation of the criterion number.
Within the limitations of time and
resources, current published information
of significance was Incorporated into the
human health assessments. Review
articles and reports were used for data
evaluation and synthesis. Scientific
judgment was exercised in reviewing
and evaluating the data in each criteria
document and in identifying the adverse
effects for which protective criteria were
published,
~ Specific health-based criteria are
developed only if a weight of evidence
supports the occurrence of the toxic
effect and if dose/response data exist
from which criteria can be-estimated.
Criteria for suspect or proven
carcinogens are presented as
concentrations in water associated with
a range of incremental cancer risks to
man. Criteria for non-carcinogens
represent levels at which exposure to a
single chemical is not anticipated to
produce adverse effects in man. In a few
cases, organoleptic (taste and odor) data
form the basis for the criterion. While
this type of criterion does not represent
a value which directly affects human
health, it is presented as an estimate of
the level of a pollutant that will not
produce unpleasant taste or odor either
directly from water consumption or
indirectly by consumption of aquatic
organisms found in ambient waters. A
criterion developed in this manner is
judged to be as useful as other types of
criteria in protecting designated water
uses. In addition, where data are
available, toxicity-based criteria are
also presented for pollutants with
derived organoleptic criteria. The choice
of criteria used in water quality
standards for these pollutants will
depend upon the designated use to be
protected. In the" case of a multiple use
water body, the criterion protecting the
most sensitive use will be applied.
Finally, for several pollutants no criteria
are recommended due to a lack of
information sufficient for quantitative
criterion formulation.
Risk Extrapolation •
Because methods do not now exist to
establish the presence of a threshold for
carcinogenic effects, EPA's policy is that
there is no scientific basis for estimating
"safe" levels for carcinogens. The
criteria for carcinogens, therefore, state
that the recommended concentration for
maximum protection of human health is
zero. In addition, the Agency has
presented a range of concentrations
corresponding to incremental cancer
risks of 10"f to 10" * (one additional case
of cancer in populations ranging from
ten million to 100,000, respectively).
Other concentrations representing
different risk levels may be calculated
by use of the Guidelines. The risk
estimate range is presented for
Information purposes and does not
represent an Agency Judgment on an
"acceptable" risk level.
Summary of the Human Health
Guidelines
The health assessments and
corresponding criteria published today
were derived based on Guidelines and
Methodology Used in the Preparation of
Health Effect Assessment Chapters of
the Consent Decree Water Criteria
Documents (the Guidelines) developed
by EPA's Office of Reserch and
Development. The estimation of health
risks associated with human exposure to
environmental pollutants requires
predicting the effect of low doses for up
to a lifetime in duration. A combination
of epldemiological and animal dose/
response data is considered the
preferred basis for quantitative criterion
derivation. The complete Guidelines are
presented as Appendix C. Major issues
associated with these Guidelines and
responses to public comments are
presented as Appendix E.
No-effect (non-carcinogen) or .
specified risk (carcinogen)
concentrations were estimated by
extrapolation from animal toxicity or
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
human epidemiology studies using the
following basic exposure assumptions: a
70-kilogram male person (Report of the
Task Croup on Reference Man,
International Commission for Radiation
Protection. November 23,1957) as the
exposed individual; the average daily
consumption of freshwater and
estuarine fish and shellfish products
equal to 6.5 grams/day; and the average.
ingestiott of two liters /day of water
(Drinking Water and Health, National
Academy of Sciences, National
Research Council, 1977). Criteria based
on these assumptions are estimated to
be protective'of an adult male who
experiences average exposure
conditions.
Two basic methods were used to
formulate health criteria, depending on
whether the prominent adverse effect
was cancer or other toxic
manifestations. The following sections
detail these methods,
Carcinogens
Extrapolation of cancer responses
from high to low doses and subsequent
risk estimation from animal data is
performed using a linearized multi-stage
model. This procedure is flexible enough
to fit all monotonlcally-increasing dose
response data, since it incorporates
several adjustable parameters. The
multi-stage model Is a linear non-
threshold model as was the* "one-hit"
model originally used in the proposed
criteria documents. The linearized multi-
stage model and its characteristics are
described fully in Appendix C. The
linear non-threshold concept has been
endorsed by the four agencies in the
Interagency Regulatory Liaison Group
and is less likely to underestimate risk
at the low dosestypical of
environmental exposure than .other
models that could be used. Because of
the uncertainties associated with dose
response, animal-to-human
extrapolation and other unknown
factors, because of the use of average
exposure assumptions, and because of
the serious public health consequences
that could result if risk were
underestimated, EPA believes that it is
prudent to use conservative methods to
estimate risk in the water quality
criteria program. The linearized
multistage model Is more systematic and
invokes fewer arbitrary assumptions
than the "one-hit" procedure previously
used.
It should be noted that extrapolation
models provide estimates of risk since a
varitey of assumptions are built.into any
model. Models using widely different
assumptions may produce estimates
ranging over several orders of
magnitude. Since Ihere is at present no
way to demonstrate the scientific
validity of any model, the use of risk
extrapolation models Is a subject of
debate in the scientific community.
However, risk extrapolation Is generally
recognized as .the only tool available at
this time for estimating the magnitude of
health hazards associated with non-
threshold toxicants and has been
endorsed by numerous Federal agencies ,
and scientific organizations, including
EPA's Carcinogen Assessment Croup,
the National Academy of Sciences, and
the Interagency Regulatory Liaison
Group as a useful means of assessing
the risks of exposure to various
carcinogenic pollutants.
Non-Carcinogens
Health criteria based on toxic effects
of pollutants other than carcinogenlcity
are estimates of concentrations which
are not expected to produce adverse
effects in humans. They are based upon
Acceptable Dally Intake (ADI) levels
and are generally derived using no-
observed-adverse-effect-level (NOAELJ
data from animal studies although
human data are used wherever
available. The ADI is calculated using
safety factors to account for
uncertainties inherent in extrapolation
from animal to man. In accordance with
the National Research Council
recommendations//W/7A7/i# Water and
Health. National Academy of Sciences,
National Research Council, 1977), safety
factors of 10,100, or 1,000 are used
depending on the quality and quantity of
data. In some instances extrapolations
are made from inhalation studies or
limits to approximate a human response
from Ingestion using the Stokinger-
Woodward model (Journal of American
Water Works Association, 1958).
Calculations of criteria from ADIs are
made using the standard exposure
assumptions {2 liters of water. 6.5 grams
of edible aquatic products, and an
average body weight of 70 kg].
Dated: October 24,1980.
Douglas M. Costle,
Administrator,
Appendix A—Summary of Water
Quality Criteria
Acenaphthene
Fresh water A qua tic Life
The available data for acenaphthene
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 1,700 fig/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of acenaphthene to
sensitive freshwater aquatic animals but
toxicity to freshwater algae occur at
concentrations as low as 520 fig/1.
Saltwater Aquatic Life »
The available data for acenaphthene
indicate that acute and chronic toxicity
to saltwater aquatic life occur at
concentrations as low as 970 and 710
fig/1, respectively, and would occur at
lower concentrations among species
that are more sensitive than those •
tested. Toxicity to algae occurs at
concentrations as low as 500 jig/1.
Human Health
Sufficient data is not available for
acenaphthene to derive a level which
would protect against the potential
toxicity of this compound. Using
available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 20 fig/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.'.
Acrolein ;;
Freshwater Aquatic Life ',•'
The* available data for acrolein
indicate that acute and chronic toxicitjr
to freshwater aquatic life occurs at •• •
concentrations as low as 68 and 21 fig/1,
respectively, and would occur at lower
concentrations among species that are
more sensitive than those tested.
Saltwater Aquatic Life
The available data for acrolein
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 55 fig/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of acrolein to sensitive
saltwater aquatic life.
Human Health . •'
For the protection of human health
from the toxic properties of acrolein
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 320 ug/1.
For the protection of human health
from the toxic properties of acrolein
ingested through contaminated aquatic
organisms alone, the ambient water
.criterion is determined to be 780 fig/I.
Acrylonitrile
Freshwater Aquatic Life
The available data for acrylonitrile
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
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79325
low as 7,550 fig/I and would occur at
lower concentrations among species
that are more sensitive than those
tested. No definitive data are available
concerning the chronic toxicity of
acrylonitrile to sensitive freshwater
aquatic life but mortality occurs at
concentrations as low as 2,600 jig/1 with
a fish species exposed for 30 days.
Saltwater Aquatic Life
.Only, one saltwater species has been
tested with acrylonitrile and no
statement can be made concerning acute
or chronic toxicity. \
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due lo exposure of acrylonitrile
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero,level may not be attainable at the .
present time. Therefore, the levels which
may result In incremental increase of
cancer risk over the lifetime are
estimated at 10~8, 10"«, and 1CT'. The
corresponding criteria are .58 ftg/1, -058
Kg/1 and .006 pg/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 8J j*g/l, .65 jig/1 and ,065 pgl
L respectively. Other concentrations
repreaenting'different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Aldrin-Dieldrin
DieldrJn
Freshwater Aquatic Life
For dieldrin the criterion to protect
fresh water aquatic life as derived using
the Guidelines is 0.0019 p.g/1 as a 24-
hour average and the concentration
should not exceed 2.5 jig/1 at any time.
Saltwater Aquatic Life
For dieldrin the criterion to protect
saltwater aquatic life as derived using
the Guidelines is 0.0019 jtg/1 as a 24-
hour average and the concentration
should not exceed 0.71 j»g/l at any time.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of dieldrin
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"», 10"*, and 10''. The
corresponding criteria are .71 ng/l, .071
ng/l. and .0071 ng/l, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the .
levels are .78 ng/l, .076 ng/l, and .0076
ng/l respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines, The
risk estimate range is presented for
Information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Aldrin
Fresh water Aquatic Life
For freshwater aquatic life the
concentration of aldrin should not
exceed 9.0 jig/1 at any time. No data are
available concerning the chronic toxicity
of aldrin to sensitive freshwater aquatic
life.
Saltwater Aquatic Life
For saltwater aquatic life the
concentration of aldrin should not
exceed 1.3 pg/1 at any time. No data are
available concerning the chronic toxicity
of aldrin to sensitive saltwater aquatic
life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of aldrin through
ingestion of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"*, 10"*, and 10~*. The
corresponding criteria are .74 ng/l, .074
ng/l. and .0074 ng/l, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are .79 ng/l, .079 ng/l, and .0079
ng/l, respectively. Other concentrations
respresenting different risk levels may
be calculated by use of the Guidelines.
The risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Antimony
Freshwater Aquatic Life
The available data for antimony
indicate that acute and chronic toxicity
to freshwater aquatic life occur at
concentrations as low as 9.000 and 1.600
ug/1. respectively, and would occur at
lower concentrations among species
that are more sensitive than those
tested. Toxicity to algae occurs at
concentrations as* low as<610 {*§/!•
Saltwater Aquatic Life
No saltwater organisms have been
adequately tested with antimony, and
no statement can be made concerning
acute or chronic toxicity.
Human Health
For the protection of human health
from the toxic properties of antimony
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 148 fig/1,
For the protection of human health
from the toxic properties of antimony
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 45,000 fig/I.
Arsenic
Freshwater Aquatic Life
For freshwater aquatic life the
concentration of total recoverable
trlvalent inorganic arsenic should not
exceed 440 pg/1 at any time. Short-term
effects on embryos and larvae of aquatic
vertebrate species have been shown to
occur at concentrations as low as 40 jig/
1.
Saltwater Aquatic Life
The available data for total
recoverable trivalent inorganic arsenic
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 508 fig/' and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of trivalent
Inorganic arsenic to sensitive saltwater
aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of arsenic
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
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79326
Federal Register / Vol. 45. No. 231 / Friday. November 2B. 1980 / Notices
estimated at 1 •,:
chronic toxicity, , . '•
Human Health ? ; ,; ^
For the maximum protection of human
health from the potential carqinogenic;
effects due to exposure of beryllium
through ingestion of contaminated wafer
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"8,10'*, and 10"'. The
corresponding criteria are 37 ng/1, 3.7
ng/1, and .37 ng/1. respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 641 ng/1,84.1 ng/1, and 6,41
ng/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
' risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Cadmium
Freshwater Aquatic Life
For total recoverable cadmium the
criterion (in M8/1) to protect freshwater
aquatic life as derived using the
Guidelines is the numerical value given
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
79327
w „„ „ 24_nour
average and the concentration (in fig/1)
should not exceed the numerical value
given by e" » U«««*H«H-»-I* at any
time. For example, a hardnesses of 50,
ICO, and 200 mg/1 as CaCO, the criteria
are 0.012,0.025, and 0.051 fig/1.
respectively, and the concentration of
total recoverable cadmium should not
exceed 1.5, 3.0 and 6.3 pg/i, respectively,
at any time.
Saltwater Aquatic Life
For total recoverable cadmium the
criterion to protect saltwater aquatic life
as derived using the Guidelines is 4.5
fig/1 as a 24-hour average and the
concentration should not exceed 59 fig/1
at any time.
Human Health
. The ambient water quality criterion
for cadmium is recommended to be
identical to the existing drinking water
standard which is 10 fig/L Analysis of
the toxic effects data resulted In a
calculated level which is protective of
human health against the ingestion of
contaminated .water and contaminated
aquatic organisms. Hie calculated value
is comparable to the present standard.
For this reason a selective criterion
based on exposure solely from
consumption of 6.5 grams of aquatic
organisms was not derived-
Carbon Tetrachloride
Freshwater Aquatic Life
The available date foir carbon
tetrachloride indicate that acute toxicity
to freshwater aquatic life occurs at
concentrations as low as 35,200 fig/1 and
would occur at lower concentrations
among species that are more sensitive
than those tested. No data are available
concerning the chronic toxicity of
carbon tetrachloride to sensitive
freshwater aquatic life.
Saltwater Aquatic Life ;
The available data for carbon
tetrachloride indicate that acute toxicity
to saltwater aquatic life occurs at
concentrations as low as 60,000 ftg/1 and
would occur at lower concentrations
among species that are more sensitive
that those tested. No data are available
concerning the chronic toxicity of
carbon tetrachloride to sensitive
saltwater aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of carbon
tetrachloride through ingestion of
contaminated water and contaminated
aquatic organisms the ambient water
concentration should be zero based on
the non-threshold assumption for this -
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental Increase of cancer risk over
the lifetime are estimated at 10"*, 10~*..
and 10~T. The corresponding criteria are
4.0ftg/l, .40f»g/I, and.04 fig/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 8&4 fig/L8.94 • •
fig/L and .69 fig/L respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
Judgment on an "acceptable" risk level.
Chlordane ,
Freshwater Aquatic Ufe
For chlordane the criterion to protect
freshwater aquatic life as derived using
the Guidelines la 0.0043 fig/I as a 24-
hour average and the concentration
should not exceed 2.4 fig/1 at any time.
Saltwater Aquatic Ufe
For chlordane the criterion to protect
saltwater aquatic life as derived using
the Guidelines is 0.0040 fig/1 as a 24-
hour average and the concentration
should not exceed 0.09 fig/1 at any time.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of chlordane
through ingestlon of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore,; the levels which
may result in Incremental increase of
cancer risk over the lifetime are
estimated at lO'VlO^, and .10'f. The
corresponding criteria are 4.6 ng/L ,46
ng/1, and .046 ng/L respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 4J8 rig/1, .48 ng/1, and .046 ng/
1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency Judgment on an
"acceptable" risk level.
Chlorinated Benzenes
Freshwater Aquatic Life
The available data for chlorinated
benzenes indicate that acute toxicity to
freshwater aquatic life occurs at
concentrations as low as 250 fig/1 and
would occur at lower concentrations
among species that are more sensitive
than those tested. No data are available
concerning the chronic toxicity of the
more toxic of the chlorinated benzenes
to sensitive freshwater aquatic life but
toxicity occurs at concentrations as low
as 50 fig/1 for a fish species exposed for
7.5 days.
Saltwater Aquatic L/fe
The available data for chlorinated
benzenes Indicate that acute and
chronic toxicity to saltwater aquatic life
occur at concentrations as low as 160
and 129 fig/1, respectively, and would
occur at lower concentrations among
species that are more sensitive than
those tested.
Human Health •
. For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of ' • .
hexachlorobenzene through ingestion of
contaminated water and contaminated
aquatic:organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result In
Incremental increase of cancer risk over
the lifetime are estimated at 10"', 10'*,
and icr*. The corresponding
recommended criteria are 7.2 ng/1, .72
ng/1, and .072 ng/1. respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 7.4 ng/1, .74 ng/1, and .074 ng/
1, respectively.
For the protection of human health
from the toxic properties of 1,2,4,5-
tetrachlorobenzene ingested through
water and contaminated'aquatic
organisms, the ambient water criterion
is determined to be 38 fig/L
For the protection of human health
from the toxic properties of 1,2,4,5-
tetrachlorobenzene ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 48 fig/1..
For the protection of human health
from the toxic properties of
pentachlorobenzene ingested through
water and contaminated aquatic
organisms, the ambient water criterion
is determined to be 74 fig/1.
For the protection of human health
from the toxic properties of
pentachlorobenzene ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 85 ftg/1.
Using the present guidelines, a
satisfactory criterion cannot be derived
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78328
Federal Register / Vol. 45. No. 231 / Friday. November 28. 19flQ / Notices
at this time due to the insufficiency in
the available data for trichlorobenzene.
For comparison purposes, two
approaches were used to derive
criterion levels for monochlorobenzene.
Based on available toxicity data, for the
protection of public health, the derived
level is 488 MS/1- Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 20
fig/1. It should be recognized that
organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Chlorinated Ethanes
Freshwater Aquatic Life
The available freshwater data for
chlorinated ethanes indicate that
toxicity increases greatly with
increasing chlorinetion, and that acute
toxicity occurs at concentrations as low
as 118,000 fig/1 for 1,2-dichloroethane.
18.000 fig/1 for two trichloroethanes.
9,320 fig/1 for two tetrachloroethanes,
7,240 fig/1 for pentachloroe thane, and
980 fig/1 for hexachloroe thane. Chronic
toxicity occurs at concentrations as low
as 20.000 fig/1 for 1,2-dichloroethane,
9,400 M8/I for 1.1.2-trichloroethane, 2,400
fig/1 for 1.1,2.2,-tetrachloroethane, 1.100
jig/1 for pentachloroethane. and 540 fig/I
for hexachloroethane. Acute and
chronic toxicity would occur at lower
concentrations among species 'that are
more sensitive than those tested.
Saltwater Aquatic Life
The available saltwater data for
chlorinated ethanes Indicate that
toxicity Increases greatly with
increasing chlorination and that acute
toxicity to fish and invertebrate species
occurs at concentrations as low as ~
113,000 fig/1 for 1.2-dichloroethane,
31,200 fig/1 for 1,1.1-trichloroe thane,
6.020 fig/1 for 1,1,2,2-tetrachloroethane,
300 fig/1 for pentachloroethane, and 940
fig/1 for hexachloroethane. Chronic
toxicity occurs at concentrations as low
as 281 fig/1 for pentachloroethane. Acute
and chronic toxicity would occur at
lower concentrations among species
that are more sensitive than those
tested.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of 1,2-di-
chloroethane through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
tile non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated at 10~s, 10"*,
and 10"*. The corresponding criteria are
9.4 fig/1. .94 fig/1, and .094 fig/1,
respectively. If the above estimates are
made for consumption of aquatic
. organisms only, excluding consumption
of water, the levels are 2,430 fig/1, 243
ftg/1. and 24.3 fig/1 respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
Is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
For the protection of human health
from the toxic properties of 1,1,1-
trichloroethane ingested through water
and contaminated aquatic organism, the
ambient water criterion is determined to
bel8.4mg/l.
For the protection of human health
from the toxic properties of l.l.l.-tri-
chloroethane ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 1*03 g/L
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of 1,1,2,-
trichloroethane through ingeslion of *
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption; for this
chemical. However, zero level may not
be- attainable at the present time.:
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated atlO~*. 10'6.
and 10"'. The corresponding criteria are
6.0 fig/1. ,B fig/1, and .06 fig/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 418 fig/1,41.8
fig/1, and 4J8 fig/1 respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of 1,1,2,2-tetra-
chloroethane through Ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated at 10**, 10"*,
and 10~*. The corresponding criteria are
1.7 fig/1, .17 fig/1, and .017 ftg/l,
respectively. Ifthe above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 107 fig/1,10.7
ftg/1. and 1.07 fig/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines, The risk estimate range
is presented for information purposes,
and does not represent an Agency
Judgment on an "acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of hexa-
chloroethane through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which, may result in
incremental increase of cancer risk over
the lifetime are estimated at 10**, 10"*,
and 10" *. The corresponding criteria are
19 fig/L 1.8 MS/1. and ,li fig/1.
respectively. If the above estimates are ,
made for consumption of aquatic /'
organisms only, excluding consumption ,
of water, the levels are 87.4 fig/1, 8.74
fig/1; and .87 fig/I, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines, The risk estimate range
is presented for information purposes
and does not represent an Agency -:
judgment on an "acceptable" risk level. ()
Using the present guidelines, a
satisfactory criterion cannot be derived "
at this time due to the insufficiency in
the available data for
monochloroethane.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for 1,1,-
dichloroethane.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for 1.1,1,2-
tetrachloroe thane.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for
pentachloroethane.
Chlorinated Naphthalenes
Freshwater Aquatic Life
The available data for chlorinated
naphthalenes Indicate that acute
toxicity to freshwater aquatic life occurs
at concentrations as low as 1,600 ftg/1
and would occur at lower
concentrations among species that are
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Federal Register / Vol. 45. No. 231 / Friday, November 28. 1980 / Notices^
79329
more sensitive than those tested. No
data are available concerning the
chronic toxicity of chlorinated
naphthalenes to sensitive freshwater
aquatic life,
Saltwater Aquatic Life
The available data for chlorinated
napthalenes indicate that acute toxicity
to saltwater aquatic life occurs at
concentrations as low as 7.5 ^g/1 and
would occur at lower, concentrations
among species that are more sensitive
than those tested No data are available
concerning the chronic toxicity of
chlorinated naphthalenes to sensitive
saltwater aquatic life.
Human Health
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for chlorinated
napthalenes.
Chlorinated Phenols
Freshwater Aquatic Life
.The available freshwater data for
chlorinated phenols indicate that
toxicity generally increases with
.increasing chlorineUon, and that acute
toxicity occurs at concentrations as low
as 30 jig/1 for 4-chloro-3-methylphenol to
greater than 500,000 pg/1 for other
compounds. Chronic toxicity occurs at
concentrations as low as 970 pg/l for
2,4,6-trichlorophenol. Acute and chronic
toxicity would occur at lower
concentrations among species that are
more sensitive than those tested.
Saltwater Aquatic Life
The available saltwater data for
chlorinated phenols indicate that
toxicity generally increases with
increasing chlorination and that acute
toxicity occurs at concentrations as low
as 440 ^g/1 for 2,3,5,6-tetrachlorophenol
and 29,700 jtg/1 for 4-chlorophenol.
Acute toxicity would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of chlorinated phenols
to sensitive saltwater aquatic life.
Human Health
Sufficient data is not available for 3-
nonochJorophenol to derive a level
•vhich would protect against the
)otential toxicity of this compound.
Jsing available organoleptic data, for
on trolling undesirable taste and odor
[uality of ambient water, the estimated
eve! is 0.1 fig/1. It should be recognized
hat organoleptic data as a basis for
stablishing a water quality criteria
ave limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 4-
monochlorophenol to derive a level
which would protect against the
potential toxicity of this compound.
Using available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 0.1 ftg/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria.
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 2,3-
dichlorophenol to derive a level which
would protect against the potential
toxicity of this compound. Using
available organoleptic data, for •
controlling undesirable taste and odor
quality of ambient water, the estimated
level is .04 j*g/l. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 2,5-
dichlorophenol to derive a level which
would protect against the potential
toxicity of this compound. Using
available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is .5 pg/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 2,6-
dichlorophenol to derive a level which
would protect against the potential
toxicity of this compound. Using
available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is .2 jig/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 3.4-
dichlorophenol to derive a level which
would protect against the potential
toxicity of this compound. Using
available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is .3 ftg/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for
2,3,4.6-tetrachlorophenoI to derive a
level which would protect against the
potential toxicity of this compound.
Using available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 1 j*g/l. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
For comparison purposes, two •
approaches were used to derive
criterion levels for 2,4,5-trichloropheriol.
Based on available toxicity data, for the
protection of public health, the derived
level is 2.6 mg/1. Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 1.0
fig/1. It should be recognized that
organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of 2,4,6-
trichlorophenol through ingestioh of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated at 10~s, 10~9,
and 10"'. The corresponding criteria are
12 fig/1,1.2 ng/1, and .12 fig/1
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 36 Mg/1,3,6 fig/1,
and .36 fig/l« respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
Using available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 2 fig/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criterion
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 2-
rnethyl-4-chlorophenol to derive a level
which would protect against any
potential toxicity of this compound.
Using available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 1800 fig/I, It should be
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79330
Federal Register / Vol. 45, No. 231 / Friday, November 28. 1980 / Notices
recognized that organoleptic data as a
basis for establishing a water quality
criterion have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data Is not available for 3-
methyl-4-chlorophenol to derive a level
which would protect against the
potential toxiclty of this compound.
Using available organoleptic data, for
•controlling undesirable taste and odor
quality of ambient water, the estimated
level is 3000 jig/I. It should be
recognized that organoleptic data as a
basis for establishing a water quality
criterion have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Sufficient data is not available for 3-
rnethyl-6-chlorophenol to derive a level
which would protect against the
potential toxicity of this compound.
Using available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 20 fig/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criterion
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Chloroalkyl Ethers
Freshwater Aquatic Ufa
. The available data for chloraalkyl
ethers indicate that acute toxicity to
freshwater aquatic life occurs at
concentrations as low as 238.000 fig/1
and would occur at lower
concentrations among species that BIB
more sensitive than those tested. No
definitive data are available concerning
the chronic toxicity of chloroalkyl ethers
to sensitive freshwater aquatic life.'
Saltwater A guatic Life
No saltwater organisms have been
tested with any chloroalkyl ether and no
statement can be made concerning acute
and chronic toxicity.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of bis-
(chloromethyl)-ether through Ingestion
of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"*, 10-«, and 10"'. The
corresponding criteria are ,038 ng/1,
.0038 ng/1. and .00038 ng/1. respectively.
If the above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 18.4 ng/1,1.84 ng/1, and .184
ng/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
'"acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of bis (2-
chloroethyl) ether through Ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental Increase of cancer risk over
the lifetime are estimated at 10'5,10"«,
and 10~\ The corresponding criteria are
.3 fig/1, .03 fig/1, and .003 fig/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 13.8 fig/1,1.38
>ig/], and .138 fig/1, respectively; Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level
For the protection of human health
from the toxic properties of bis {2-
chloroisopropyl) ether ingested through
water and contaminated aquatic
organisms, the ambient water criterion
is determined to be 34.7 fig/1.
For the protection of human health
from the toxic properties of bis {2-
chloroisopropyl) ether ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 4136 mg/1.
Chloroform
Freshwater Aquatic Life
The available data for choloroform
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 28.MO fig/1, and would occur at
lower concentrations among species
that are more sensitive than the three
tested species. Twenty-seven-day LC50
values indicate that chronic toxicity
occurs at concentrations as low as 1,240
fig/1, and could occur at lower
concentrations among species or other
life stages that are more sensitive than
the earliest life cycle stage of the
rainbow trout.
Saltwater Aquatic Life
The data base for saltwater sp|^es is
limited to one test and no statement can
be made concerning acute or chronic
toxicity.
Human Heallh
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of chloroform
through ingestlon of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"*. 10~*. and lO"*. The
corresponding criteria are 1.90 fig/1, .19
fig/1, and .019 fig/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 157 jig/1,15.7 fig/1, and 1.57
fig/1. respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
2-Chlorophenol
Freshwater Aquatic Life
The availabe data for 2-chlorophenol
Indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 4,380 fig/1 and would occur at
lower concentrations among species
that are more sensitive that those tested.
No definitive data are available
concerning the chronic toxicity of 2- .
chlorophenol to sensitive freshwater
aquatic life but flavor impairment occurs
in one species of fish at concentrations
as low as 2,000 ng/1.
Saltwater Aquatic Life
No saltwater organisms have been
tested with 2-chlorophenol and no
statement can be made concerning acute
and chronic toxicity.
Human Health
Sufficient data is not available for 2-
chlorophenol to derive a level which
would protect against the potential
toxicity of this compound. Using
available organoleptic data, for
controlling undesirable taste and odor
quality of ambient water, the estimated
level is 0.1 fig/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
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Federal Register / Vol. 45. No. 231 / Friday, November 28, 1980 /Notices
79331
demonstrated relationship to potential
adverse human health effects.
Chromium
Freshwater Aquatic Life
For total recoverable hexavalent
chromium the criterion to protect
freshwater aquatic life as derived using
the Guidelines is 0.29 ftg/1 as a 24-hour
average and the concentration should
not exceed 21 pg/1 at any time.
For freshwater aquatic life the
concentration (in /ig/1) of total
recoverable trivalent chromium should
not exceed the numerical value given by
'•e(1.08[ln(h8rdness}]+3.48)" at any
time. For example, at hardnesses of 60,
100 and 200 mg/1 as CaCO, the
concentration of total recoverable
trivalent chromium should not exceed
2,200,4,700. and 9.900 MS/1, respectively.
at any time. The available data indicate
hat chronic toxicity to freshwater
iquatic life occurs at concentrations as
ow a 44 jig/1 and would occur at lower
Concentrations among species that are
nore sensitive than those tested.
tali water. Aquatic Life
For total recoverable hexavalent
Chromium the criterion to protect
altwater aquatic life as derived using
he Guidelines is 18 Mg/1 as a 24-hour
verage and the concentration should
ot exceed 1,260 Mg/1 at any time.
For total recoverable trivalent
hromium, the availabe data indicate
lat acute toxicity to saltwater aquatic
fe occurs at concentrations as low as
3,300 M8/1, and would occur at lower
ancentrations amoung species that are
iore sensitive than those tested. No
3ta are available concerning the
ironic toxicity of trivalent chromium to
'.nsitive saltwater aquatic life.
umanHealth •
For the protection of human health
om the, toxic properties of Chromium
[ ingested through water and -
mtamlnated aquatic organisms, the
nbient water criterion is determined to
.'slTOtr.s/1;: ;
For protection of human health
imt .oxic properties of Chromium
ingested through contaminated
uatic organisms alone, the ambient
iter criterion is determined to be 3433
•i/i. - ^;vv,- ;....•:.;:-';-.:
The ambient water quality criterion
• total Chromium VI is recommended
be identical to the existing drinking
iter standard which is SO jig/1.
lalysis of the toxic effects data
•ulled in a calculated level which is
Hective of human health against the
estion of contaminated-water and
itnminated aquatic organisms. The
calculated value is comparable to the
present standard. For this reason a
selective criterion based on exposure
solely from consumption of 6.5 grams of
aquatic organisms was not derived.
Copper
Fresh water Aquatic Life
For total recoverable copper the
criterion to protect freshwater aquatic
life as derived using the Guidelines is 5.6
^g/1 as a 24-hour average and the ' •
concentration (in pg/1) should not
exceed the numerical value given by
e(0.94[ln(hardnes8}]-1.23) at any time.
For example, at hardnesses of 50,100.
and 200 mg/1 CaCO, the concentration
of total recoverable copper should not
exceed 12,22, and 43 /*g/l at any time.
Saltwater Aquatic Life
For total recoverable copper the
criterion to protect saltwater aquatic life
as derived using the Guideline! is 4.0
jig/1 as a 24-hour average and the
concentration should not exceed 23 j*g/l
at any time.
Human Health
Sufficient data is not available for
copper to derive a level which would
protect against the potential toxicity of
this .compound. Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 1
mg/1. It should be recognized that
organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
'Cyanide- ' ,'• ..'. .-.
FreshwaterAquaticLife
For free cyanide (sum of cyanide
present as HCN and CN~, expressed as
CM] the criterion to protect freshwater
aquatic life as derived using the
Guidelines is 3.6 jtg/1 as a 24-hour
average and the concentration should
not exceed 52 jtg/1 at any time.
Saltwater Aquatic Life
The available "data for free cyanide
(sum of cyanide present as HCN and
CN~t expressed as CN) Indicate that
acute toxicity to saltwater aquatic life
occurs at concentrations as .low as 30
Mg/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. If the
acute-chronic ratio for saltwater
organisms is similar to that for ,
freshwater organisms, chronic toxicity
would occur at concentrations as low as
2.0 Mg/1 for the tested species and at
lower concentrations among species
that are more sensitive than those
tested.
Human Health
The ambient water quality criterion
for cyanide is recommended to be
identical to the existing drinking water
standard which is 200 jig/1. Analysis of
the toxic effects data resulted in a
calculated level which is protective of
human health against the ingestion of
contaminated water and contaminated
•aquatic organisms. The calculated value
is comparable to the present standard.
For this reason a selective criterion
based on exposure solely from
consumption of 6.5 grams of aquatic
organisms was not derived.
DDT and Metabolites
Freshwater Aquatic Life :
DDT
For DDT and its metabolites the
criterion to protect freshwater aquatic
life as derived using the Guidelines is
0.0010 M8/1 as a 24-hour average and the
concentration should not exceed 1.1 M8/1
at any time.
TDE
The available data for TDE indicate
that acute toxicity to freshwater aquatic
life occurs at concentrations as low as
0.6 Mg/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of TDE to sensitive
freshwater aquatic life.
DDE
t The available data for DDE indicate
that acute'toxicity to freshwater aquatic
life occurs at concentrations as low aa
1.050 jxg/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of DDE to sensitive
freshwater aquatic life.
Saltwater Aquatic Life '
DDT
For DDT and its metabolites the
criterion to protect saltwater aquatic life
as derived using the Guidelines is 0.0010
Mg/1 as a 24-hour average and the
concentration should not exceed 0.13
Mg/1 at any time.
TDE
The available data for TDE indicate
that acute toxicity to saltwater aquatic
life occurs at concentrations as low as
3.6 Mg/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
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79332
Federal Register / Vol. 45. No. 231 / Friday. November 28. 19BO / Notices
chronic toxicity of TDE to sensitive
saltwater aquatic life.
DDE
The available data for DDE indicate
that acute toxicity to saltwater aquatic
life occurs at concentrations as low as
14 n?/l and would occur at lower
concentrations among species that are
mere sensitive than those tested. No
data are available concerning the
chronic toxicity of DDE to sensitive
saltwater aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of DDT through
Ingestion of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10~», W*. and 10"*. The
corresponding criteria are .24 ng/1, .024
ng/1. and .0024 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are .24 ng/l, .024 ng/1, and .0024
ng/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency Judgment of an
"acceptable" risk level.
Dichiorobenzenes
Freshwater Aquatic Life
The available data for
dichiorobenzenes indicate that acute
and chronic toxicity to freshwater
aquatic life occurs at concentrations as
low as 1,120 and 763 fig/1, respectively,
and would occur at lower
concentrations among species that are
more sensitive than those tested.
Saltwater Aquatic Life
The available data for
dichiorobenzenes indicate that acute
toxicity to saltwater aquatic life occurs
at concentrations as low as 1,970 jig/1
and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of dichiorobenzenes to
sensitive saltwater aquatic life.
Human Health
For the protection of human health
from the toxic properties of
dichiorobenzenes (all isomers) ingested
through water and contaminated aquatic
organisms, the ambient water criterion
is determined to be 400 Mg/1-
For the protection of human health
from the toxic properties of
dichiorobenzenes (all isomers) ingested
through contaminated aquatic organisms
alone, the ambient water criterion is
determined to be 2.8 mg/1.
•Dichlorobenzidines..
Freshwater Aquatic Life
The data base available for
dichlorobenzidines and freshwater
organisms is limited to one test on
bioconcer.tration of 3,3'-
dichlorobenzidine and no statement can
be made concerning acute or chronic
toxicity.
Saltwater Aquatic Life
No saltwater organisms have been
tested with any dichlorobenzidine and
no statement can be made concerning
acute or chronic toxicity.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of
dichlorobenzidine through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero base on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental Increase of cancer risk over
the lifetime are estimated at 10""*, 10~«,
and 10"'. The corresponding criteria are
.103 ftg/1, .0103 fig/1, and .00103 jig/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are .204 ng/1, .0204
fig/1, and .00204 fig/1, respectively.
Other concentrations representing
different risk levels may be calculated
by use of the Guidelines. The risk
estimate range is presented for .
information purposes and does not
represent an Agency Judgment on an
"acceptable" risk level.
Dichloroethylenes
Freshwater Aquatic Life
The available data for
dichloroethylenes indicate that acute
toxicity to freshwater aquatic life occurs
at concentrations as low as 11,600 fig/1
and would occur at lower
concentrations among speciea that are
more sensitive than those tested. No
definitive data are available concerning
the chronic toxicity of dichlorethylenes
to sensitive freshwater aquatic life.
Saltwater Aquatic Life
The available data for
dichlorethylenes indicate that acute
toxicity to saltwater aqua tic life occurs
at concentrations as low as 224,000 /ig/1
and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity dichioroethyleneB to
sensitive saltwater aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects duo to exposure of
1,1-dichloroethylene through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero bastd on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result In
incremental increase of cancer risk over
the lifetime are estimated at 10"'. 10'*,
and 10"'. The corresponding criteria-are
.03 Mg/1. -033 Mg/1, and .0033 Mg/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 18.5 pg/1, 1.0S
MS/1, and .185 fig/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
Judgment on an "acceptable" risk level,
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the Insufficency in the
available data for 1,2-dichloroethylene.
2,4-Dlchloropheno)
Freshwater Aquatic Life
The available data for 2,4-
dichJorophenol indicate that acute and
chronic toxicity to freshwater aquatic
life occurs at concentrations as low as
2,020 and 365 fig/1, respectively, and
would occur at lower concentrations
among species that are more sensitive
that those tested. Mortality to early life
stages of one species of fish occurs at
concentrations as low as 70 ug/l.
Saltwater Aquatic Life
Only one test has been conducted
with saltwater organisms on 2,4-
dichJorophenol and no statement can be
made concerning acute or chronic
toxicity.
Human Health
For comparison purposes, two
approaches were used to derive
criterion levels for 2,4-dichlorophenol.
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
70333
Baaed on available toxicity data, for the
protection of public health, the derived
level is 3.09 mg/1. Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 0.3
pg/j. It should be recognized that
organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential "
adverse human "health effects,
Dichloropropanes/DIchloropropenes
Freshwater Aquatic Life
The available data for '
dichloropropanes Indicate that acute
and chronic toxicity to freshwater
aquatic life occurs at concentrations as
low as 23,000 and 5,700 MS/I-
respectively, and would occur at lower
concentrations among species that are
more sensitive than those tested.
The available data for
dichloropropenes indicate that acute
and chronic toxicity to freshwater
aquatic life occurs at concentrations as
low as 6,060 and 244 ftg/1, respectively,
and would occur at lower
concentrations among species that are
more sensitive than those tested,
Saltwater Aquatic Life
The available data for
dichloropropanes indicate that acute
and chronic toxicity to saltwater aquatic
life occurs at concentrations as low as
10,300 and 3,040 pg/L respectively, and
would occur at lower concentrations
among species that are more sensitive
than those tested. .
The available data for
dlchJoropropenes Indicate that acute
toxicity to saltwater aquatic life occurs
at concentrations as low a as 780 fig/1,
and would occur at lower
concentrations among spe'cies that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of dichloropropenes to
sensitive saltwater aquatic life,
Human Health
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for dichloropropanes.
For the protection of human health
from the toxic properties of
dichloropropenes ingested through
water and contaminated aquatic
organisms, the ambient water criterion
is determined to be 87 jig/I.
For the protection of human health
from the toxic properties of
dichloropropenes ingested through
contaminated aquatic organisms alone.
the ambient water criterion is
determined to be 14.1 mg/1.
2,4-Dunethylphenol
Fresh water A qua tic Life
The available data for 2,4-
dimethylphenol Indicate that acute
toxicity to freshwater aquatic life occurs
at concentrations as low as 2,120 jtg/1
and would occur at lower
concentrations among species .that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of dlmethylpnenol to
sensitive freshwater aquatic life.
Saltwater Aquatic Life
No saltwater organisms have been
tested with 2,4-dimethylphenol and no
statement can be made concerning acute
and chronic toxicity.
Human Health
Sufficient data are not available for
2,4-dimethylphenol to derive a level
which would protect against the
potential toxicity of this compound.
Using available organoleptic data, for
controlling undersirable taste and odor
quality of ambient water, the estimated
level is 400 ug/1. It should be recognized
that organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
2,4-Dlnitrotoluene
Freshwater Aquatic Life
The available data for 2,4-
dinitrotoluene Indicate that acute and
chronic toxicity to freshwater aquatic
life occurs at concentrations as low as
330 and 230 jtg/1, respectively, and
would occur at lower concentrations
among species that are more sensitive
than those tested.
Saltwater Aquatic Life
The available data for 2,4-
dinitrotoluenes indicate that acute
toxicity to saltwater aquatic life occurs
at concentrations as low as 590 fig/1 and
would occur at lower concentrations
among species that are more sensitive
than those tested. No data are available
concerning the chronic toxicity of 2,4-
dinitrotoluenes to sensitive saltwater
aquatic life but a decrease In algal cell
numbers occurs at concentrations as
low as 370 ftg/1.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of 2,4-
dinitrotoluene through ingestlon of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated at 10~*. 10"«,
and 10"'. The corresponding criteria are
1.1 MS/I. O.ll.Mg/1. and 0.011 pg/1,
' respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 01 j*g/l,8.1 j*g/l,
and 0.91 fig/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
1,2-Dlphenylhydrazlne
freshwater Aquatic Life
The available data for 1,2-
diphenylhydrazlne indicate that acute
toxicity to freshwater aquatic life occurs
at concentrations as low as 270 fig/1 and
would occur at lower concentrations
among species that are more sensitive
than those tested. No data are available
concerning the chronic toxicity of 1,2-
dlphenylhydraiine to sensitive
freshwater aquatic life.
Saltwater A qua tic Life
No saltwater organisms have been
tested with 1,2-diphenylhydrazine and
no statement can be made concerning
acute and chronic toxicity.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of 1,2-
diphenylhydrazine through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result In
incremental Increase of cancer risk over
the lifetime are estimated at 10~*. 10~*.
and 10"'. The corresponding criteria are
422 ng/1,42 ng/1, and 4 ng/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 5.8 ng/1. 0.56
iug/l, and 0.058 jig/1, respectively.
Other concentrations representing'
different risk levels may be calculated
by use of the Guidelines. The risk
estimate range is presented for
information purposes and does not
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79334
Federal Register / Vol. 45, No. 231 / Friday. November 28. 1980 / Notices
represent an Agency judgment on an
"acceptable" risk level.
Endosulfan,
Fresh water Aquatic Life
For endosulfan the criterion to protect
freshwater aquatic life as derived using
the Guidelines is 0.056 Mg/1 as a 24-hour
average and:the concentration should
not exceed 0.22 jxg/1 at any time.
Saltwater Aquatic Life
For endosulfan the criterion to protect
saltwater aquatic life as derived using,
the Guidelines is 0.0087 fig/1 as a 24-
. hour average and the concentration
should not exceed 0.034 jxg/1 at any
time.
Human Health
For the protection of human health
from the toxic properties of endosulfan
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 74 MS/1-
For the protection of human health
from the toxic properties of endosulfan
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 159 jxg/1.
Endiin
Freshwater Aquatic Ufe
For endrin the criterion to protect
freshwater aquatic life as derived using
the Guidelines is 0.0023 pg/ras a 24-
hour average and the concentration
should not exceed 6.18 jxg/1 at any tinie.
Saltwater Aquatic Life •
For endrin the criterion to protect
saltwater aquatic life as derived using
the Guidelines is 0.0023 MS/I as a 24-
hour average and the concentration
should hot exceed 0.037 /ig/1 at any
time.
Human Health
The ambient water quality criterion
for endrin is recommended to be
identical to the existing drinking water
standard which is 1 /ig/1. Analysis of the
toxic effects data resulted In a
calculated level which is protective of
human health against the ingestion of
contaminated water and contaminated
aquatic organisms. The calculated value
is comparable to the present standard.
For this reason a selective criterion
based on exposure solely from
consumption of 6.5 grams of aquatic
organisms was not derived.
Ethylbenzene
Freshwater Aquatic Life
The available data for ethylbenzene
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 32,000 fig/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No definitive data are available
concerning the chronic toxicity of
ethylbenzene to sensitive freshwater
aquatic life.
Saltwater Aquatic Life
The available data for ethylbenzene1
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 430 pg/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of ethylbenzene to
sensitive saltwater aquatic life.
Human Health
For the protection of human health
from the toxic properties of
ethylbenzene ingested through water
and contaminated aquatic organisms,
the ambient water criterion is
determined to be 1.4 mg/1.
For the protection of human health
from the toxic properties of
ethylbenzene Ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 3.28 mg/1. ,
Fluoranthene
Freshwater Aquatic Life
The available data for fluoranthene
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 3960 jxg/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of fluoranthene to
sensitive freshwater aquatic life.
Saltwater Aquatic Life
The available data for fluoranthene
Indicate that acute and chronic toxicity
to saltwater aquatic life occur at
concentrations as low as 40 and 18 /ig/1,
respectively, and would occur at lower
concentrations among species that are
more sensitive than those tested.
Human Health
For the protection of human health
from the toxic properties of fluoranthene
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be42/tg/J.
For the protection of human health
from the toxic properties of fluoranthene
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 54 MS/'-
Haloethere
Freshwater Aquatic Life
The available data for haloethers •'
indicate that acute and chronic toxicity
to freshwater aquatic life occur at •'•'••• •'",'
concentrations as low as 360 and 122
fig/I. respectively, and would occur at
lower concentrations among species
that are more sensitive than those
tested".'
Saltwater Aquatic Life
No saltwater organisms have'been ..'•
tested with any haloether and no . .
statement can be made concerning acute
or chronic toxicity.
Human Health
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for haloethers.
Halomethanes
Freshwater Aquatic Life
The available data for halomethanes
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 11.000 Mg/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of halomethanes to :
sensitive freshwater aquatic life.
Saltwater Aquatic Life
The available data for halomethanes
indicate that acute and chronic toxicity
to saltwater aquatic life occur at
concentrations as low as 12,000 and
6,400 Mg/1. respectively, and would
occur at lower concentrations among
species that are more sensitive than
those tested. A decrease in algal cell
numbers occurs at concentrations as
low as 11,500 fig/1.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of
chloromethane, bromomethane.
dichloromethane,
bromodichloromethane,
tribromomethane,
dichlorodifluoromethane,
trichlorofluoromethane, or combinations
of these chemicals through ingestion of
contaminated, water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk, over
the lifetimes are estimated at 10~5,10~6.
and 10"7. The corresponding criteria are
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices 79335
1.9 fig/1, 0.19 ftg/1, and 0.019 fig/I,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 157 fig/1,15.7
fig/1, and 1.57 ^g/1, respectively. Other
concentrations representing different
risk.levela may be calculated by use of
the Guidelines. The risk estimate range
is presented far information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
Heptachlor
Freshwater Aquatic Life
For heptachlor the criterion to protect
freshwater aquatic life as derived using
the Guidelines is 0.0038 jig/1 as a 24-
hour average and the concentration
should not exceed 0.52 fig/1 at any time.
Saltwater Aquatic Life
For heptachlor the criterion to protect
saltwater aquatic life as derived using
the Guidelines is 0.0036 f»g/l aa a 24-
hour average and the concentration
should not exceed 04)53 fig/1 at any
time.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of heptachlor
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result In Incremental Increase of
cancer risk, over the lifetimes are
estimated at 10"», 10'«, and 10"f. The
corresponding criteria are 2.78 ng/1, .28
ng/1, and .028 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 2.85 ng/1, ,28 ng/1, and ,028
ng/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
Hexachlorobutadlene
Freshwater Aquatic Life
The available data for
hexachlorobutadiene indicate that acute
and chronic/toxicity to freshwater
aquatic life occur at concentrations as
low as 90 and 9.3 fig/1, respectively, and
would occur at lower concentrations
among species that are more sensitive
•-ban those tested.
Saltwater Aquatic Life
The available data for
hexachlorobutadiene indicate that acute
toxicity to saltwater aquatic life occurs
at concentrations as low as 32 fig/1 and
would occur at lower concentrations
among species that are more sensitive
that those tested. No data are available
concerning the chronic toxicity of
hexachlorobutadiene to sensitive
saltwater aquatic life
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of
hexachlorobutadiene through ingestion
of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk, over the lifetimes are
estimated at 10"5,10"8, and 10" \ The
corresponding criteria are 4.47 fig/1,0.4S
jig/1, and 0.045 fig/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 900 fig/1,50 fig/1, and 6 fig/1
respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency Judgment on an
"acceptable" risk level.
Hexachlorocydohexane
Undone
Freshwater Aquatic Life
For Lindane the criterion to protect
freshwater aquatic life aa derived using
the Guidelines la 0.080 fig/1 as a 24-hour
average and the concentration should
not exceed Z.O.fig/l at any time.
Saltwater Aquatic Life
For saltwater aquatic life the
concentration of lindane should not
exceed 0.16 fig/1 at any time. No data
are available concerning the chronic
toxicity of lindane to sensitive saltwater
aquatic life.
BHC
Freshwater Aquatic Life
The available date for a mixture of
isomers of BHC indicate that acute
toxicity to freshwater aquatic life occurs
at concentrations as low as 100 fig/1 and
would occur at lower concentrations
among species that are more sensitive
than those tested. No data are available
concerning the chrorJc tox:ci;y of a
mixture of isomers of BHC to sensitive
freshwater aquatic life.
Saltwater Aquatic Life
The available date for a mixture of
isomers of BHC indicate that acute
toxicity to saltwater aquatic life occurs
at concentrations as low as 0.34 fig/1
and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of a mixture of isomers
of BHC to sensitive saltwater aquatic
life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of alpha-HCH
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk, over the lifetimes are
estimated at 10"8.10~«, and 10"'. The
corresponding criteria are 92 ng/1,9.2
ng/1, and .92 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 310 ng/1, 31.0 ng/1, and 3.1
ng/1 respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range Is presented for
Information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of beta-HCH
through ingestion cf contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for tola chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result In incremental increase of
cancer risk, over the lifetimes are
estimated at lO"8.1CT«, and 10'*. The
corresponding criteria are 163 ng/L 16.3
ng/l,-and 1.63 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 547 ng/1,54.7 ng/L and 5.47
ng/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
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79336
Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
represent an Agency Judgment on an
"acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of tech-HCH
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical. However.
zero level may not be attainable at the
present time. Therefore, the levels which
may result in Incremental increase of
cancer risk, over the lifetimes are
estimated at 10~s. ID"6, and 10"T. The
corresponding criteria are 123 ng/l. 12.3
ng/1. and T.23 ng/l, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 414 ng/l, 41.4 ng/l, and 4.14
ng/l, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of gamma-HCH
through Ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentrations
should be zero based on the non-
threshold assumption for this chemical.
However, zero level may not be
attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated at ICT", 10~6,
and 1CT7. The corresponding criteria are
186 ng/l 18.6 ng/l, and 1.86 ng/l
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 625 ng/l, 62.5
ng/l, 6.25 ng/l, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for delta-HCH.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for epsilon-HCH.
Hexachlorocyclopentadlene
Freshwater Aquatic Life
The available data for
hexachlorocyf lopentadiene indicate that
acute and chronic toxicity to freshwater
aquatic life occurs at concentrations as
low as 7.0 and 5.2 jig/1, respectively, and
would occur at lower concentrations
among species that are more sensitive
than those tested.
Saltwater Aquatic Life
The available data to
hexachlorocyclopentadiene indicate that
acute toxicity to saltwater aquatic life
occurs at concentrations as low as 7.0.
p.g/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of
hexachlorocyclopentadiene to sensitive
saltwater aquatic life.
Human Health
For comparison purposes, two
approaches were used to derive
criterion levels for
hexachlorocyclopentadiene. Based on
available toxicity data, for the
protection of public health, the derived
level is 206 jig/1. Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 1.0
fig/1. It should be recognized that
organoleptic data as a basis for
establishing a water quality criterion
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Isophorone
Freshwater Aquatic Life
The available data for isophorone
indicate that acute toxicity to freshwater
aquatic life ocurs at concentrations as
low as 117,000 M8/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning-
the chronic toxicity of isophorone to
sensltive'freshwater aquatic life.
Saltwater Aquatic Life .
The available data for isophorone
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 12,900 jig/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of isophorone to
sensitive saltwater aquatic life.
Human Health
For the protection of human health
from the toxic properties of isophorone
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 5.2 mg/1.
For the protection of human health
from the toxic properties of isophorone
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 520 mg/L
Lead
*
Freshwater Aquatic Life
For total recoverable lead the
criterion (in jig/1) to protect freshwater
aquatic life as derived using the
Guidelines is the numerical value given
by e(2.35[ln(hardness)]-9.48) as a 24-
hour average and the concentration (in
fig/1) should not exceed the numerical
value given by e(1.22[ln(hardness)]-0.47J
at any time. For example, at hardnesses
of 50,100, and 200 mg/1 as CaCO, the
criteria are 0.75,3.8. and 20 fig/1.
respectively, as 24-hour averages, and
the concentrations should not exceed 74,
170. and 400 fig/I, respectively, at any
time.
Saltwater Aquatic Life
The available data for total
recoverable lead indicate that acute and
chronic toxicity to saltwater aquatic life
occur at concentrations as low as 666
and 25 fig/l, respectively, and would
occur at lower concentrations among
species that are more sensitive than
those tested.
Human Health
The ambient water quality criterion
for lead is recommended to be identical
to the existing drinking water standard
which is 50 fig/1. Analysis of the toxic
effects data resulted in a calculated
level which is protective to human
health against the ingestion of
contaminated water and contaminated
aquatic organisms. The calculated value
is comparable to the present standard.
For this reason a selective criterion
based on exposure solely from
consumption of 6.5 grams of aquatic
organisms was not derived.
Mercury
Freshwater Aquatic Life
For total recoverable mercury the
criterion to protect freshwater aquatic
life as derived using the Guidelines is
0.00057 fig/1 as a 24-hour average and
the concentration should not exceed
0.0017 fig/1 at any time.
Saltwater Aquatic Life
For total recoverable mercury the
criterion to protect saltwater aquatic life
as derived using the Guidelines is 0.025
fig/I as a 24-hour average and the
concentration should not exceed 3.7 fig/I
at any time.
Human Health
For the protection of human health
from the toxic properties of mercury
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79337
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 144 ng/1.
For the protection of human health
from the toxic.properties of mercury
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 146 ng/1.
Note.—These values Include the
consumption of freshwater, estuarine. and
marine species.
Naphthalene
Freshwater Aquatic Life
The available data to naphthalene
indicate that acute and chronic toxicity
to freshwater aquatic life occur at
concentrations as low as 2.300 and 620
•j.g/1 respectively, and would occur at
lower concentrations among species
that are more sensitive than those
tested.
Saltwater Aquatic Life
The available data for naphthalene
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 2,350 Mg/1 and would occur at
lower concentrations among species
hat are more sensitive than those
ested. No-data are available concerning
he chronic toxicity of naphthalene to
.snsltive saltwater aquatic life.
iuman Health
Using the present guidelines, a
atisfactory criterion cannot be derived
t this time due to the insufficiency in
.ie available data for naphthalene.
i'ickel
'reshwaterAquatic Life
For total recoverable nickel the
riterion (in Mg/1) to protect freshwater
quatic life as derived using the
tiidelines is the numerical value given
y e(0.76 [In (hardness)] +1.06) as a 24-
aur average and the concentration (in
3/1) should not exceed the numerical
ilue given by e(0.76[ln (hardness)] +
02) at any time. For example, at
irdnesses of SO, 100, and 200 mg/1 as
aCO, the criteria are SO, 06, and 160
;/']. respectively, as 24-hour averages,
id the concentrations should not
ceed 1.100.1,800, and 3,100 jig/1,
apectively, at any time.
i(water Aquatic Life
For total recoverable nickel the
terion to protect saltwater aquatic life
derived using the Guidelines is 7.1
/I as a 24-hour average and the
acentration should not exceed 140 /ig/
t any time.
Human Health
For the protection of human health
from the toxic properties of nickel
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 13.4 Mg/1-
For the protection of human health
from the toxic properties of nickel
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 100 /ig/1.
Nitrobenzene
Freshwater Aquatic Life
The available data for nitrobenzene
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 27,000 Mg/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No definitive data are available
concerning the chronic toxicity of
nitrobenzene to sensitive freshwater
aquatic life.
Saltwater A quatic Life
The available data for nitrobenzene
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 0,680 Mg/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of nitrobenzene to
sensitive saltwater aquatic life.
Human Health
For comparison purposes, two
approaches were used to derive
criterion levels for nitrobenzene. Based
on available toxicity data, for the
protection of public health, the derived
level is 19.8 mg/1. Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 30
^g/1. It should be recognized that
organoleptic data as a basis for
establishing a water quality criteria
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Nltrophenols
Freshwater Aquatic Life
The available data for nitrophenols
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 230 /ig/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of nitrophenols to
sensitive freshwater aquatic life but
toxicity to one species of algae occurs at
concentrations as low as 150 Mg/1-
Saltwater Aquatic Life
The available data for nitrophenols
indicate that acute toxicity to saltwater
aquatic life occurs at concentrations as
low as 4.850 MS/' &na would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of nitrophenols to
sensitive saltwater aquatic life.
Human Health
For the protection of human health
from the toxic properties of 2,4-dinitro-o-
cresol ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 13.4 Mg/1.
For the protection of human health
from the toxic properties of 2,4-dinitro-o-
cresol ingested through contaminated
aquatic organisms alone, the ambient
water criterion is determined to be 765
For the protection of human health
from the toxic properties of
dinitrophenol ingested through water
and contaminated aquatic organisms.
the ambient water criterion is
determined to be 70 Mg/1.
For the protection of human health
from the toxic properties of
dinitrophenol ingested through
contaminated aquatic organisms alone.
the ambient water criterion is
determined to be 14.3 mg/1.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for mononitrophenol.
Using the present guidelines, a
satisfactory criterion cannot be derived
at this time due to the insufficiency in
the available data for tri-nitrophenol.
Nltrosamines
Fresh water Aquatic Life
The available data for nitrosamines
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
• low as 5,850 Mg/1 and would occur at
lower concentrations among species
.that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of nitrosamines to
sensitive freshwater aquatic life.
Saltwater Aquatic Life
The available data for nitrosamines
indicate that acute toxicity to saltwater'
aquatic life occurs at concentrations as
low as 3.300,000 Mg/1 and would occur at
lower concentrations among species '
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of nitrosamines to
sensitive saltwater aquatic life.
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79338
Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of n-
nitrosodlmethylamine through ingestion
of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical.-However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk, over the lifetimes are
estimated at I0~», W8, and 10~f. The
corresponding criteria are 14 ng/1,1,4
ng/1, and .14 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 180,000 ng/1,16,000 ng/1, and
1,600 ng/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for Information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of n-
nitrosodiethylamine through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water ~
concentration should be zero based on
the non-threshold assumption for this
chemical However, zero level may not
be~attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk, over
the lifetimes are estimated at 10~*. 10~c,
and 10"'. The corresponding criteria are
8 ng/1,0.8 ng/1, and 0.08 ng/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 12,400 ng/1, 1,240
ng/1, and 124 ng/L respectively. Other
concentrations representing different •
risk levels may be calculated by use of
the Guidelines. The risk estimate range
Is presented for information purposes
and doe's not represent an Agency
judgment on an "acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure in n-nitrosodi-n-
butylamine through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk, over
the lifetimes are estimated at 10~s, 10~*.
and 10"'. The corresponding criteria are
64 ng/16.4 ng/1 and .064 ng/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 5,868 ng/1, 587
ng/1, and 58.7 ng/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure In n-
nitrosodiphenylamine through Ingestion
of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
* zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk, over the lifetimes are
estimated at 10""°. 10"*, and 10"I The
corresponding criteria are 48,000 ng/1
4,900 ng/1 and 490 ng/I, respectively. If
the above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 161,000 ng/1,16.100 ng/1, and
1,610 ng/1, respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
judgment on an "acceptable" risk level.
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure in n-
nitrosopyrrolidine through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk, over
the lifetimes are estimated at 10"*, 10"*
and 10"7. The corresponding criteria are
160 ng/116.0 ng/1 and 1.60 ng/1.
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 919.000 ng/1,
91.900 ng/1, and 9,190 ng/1. respectively.
Other concentrations representing
different risk levels may be calculated
by use of the Guidelines. The risk
estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Pentachlorophenol
Fresh water Aquatic Life
The available data for •
pentachlorophenol indicate that acute
and chronic toxicity to freshwater
aquatic life occur at concentrations as
low as 55 and 3.2 pg/1, respectively, and
would occur at lower concentrations
among species that are more sensitive
than those tested.
Saltwater Aquatic Life
The available data for
pentachlorophenol Indicate that acute
and chronic toxicity to saltwater aquatic
life occur at concentrations' as low as 53
and 34 MS/1- respectively, and would
occur at lower concentrations among
species that are more sensitive than
those tested.
Human Health
For comparison purposes, two
approaches were used to derive
criterion levels for pentachlorophenol.
Based on available toxicity data, for the
protection of public health, the derived
level is 1.01 ing/1. Using available
organoleptic data, for controlling
undesirable taste and odor quality of
ambient water, the estimated level is 30
Hg/l.'It should be recognized that
organoleptic data as a basis for
establishing a water quality criterion
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Phenol
Fresh water A qua tic Life
The available data for phenol indicate
that acute and chronic toxicity to
freshwater aquatic life occur at
concentrations as low as 10.200 and
2,580 jtg/1, respectively, and would
occur at lower concentrations among
species that are more sensitive than
those tested,
Saltwater Aguatic Life
The available data for phenol indicate
that acute toxicity to saltwater aquatic
life occurs at concentrations as low as
5,800 ug/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of phenol to sensitive
saltwater aquatic life.
Human Health
For comparison purposes, two
approaches were used to derive
criterion levels for phenol. Based on
available toxicity data, for the
protection of public health, the derived
level is 3.5 rng/1. Using available
organoleptic data, for controlling
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Federal Register / Vol. 45, No. 231 / Friday, November 28. 1980 / Notices
79339
undesirable taste and odor quality of
ambient water, the estimated level Is 0.3
mg/1. It should be recognized that
organoleptic data as a basis for
establishing a water quality criterion
have limitations and have no
demonstrated relationship to potential
adverse human health effects.
Phthalate Esters
Freshwater Aquatic Life
The available data for phthalate
esters indicate that acute and chronic
toxidty to freshwater aquatic life occur
at concentrations as low as 940 and 3
fig/1, respectively, and would occur at
lower concentrations among species
that are more sensitive than those
tested.
Saltwater Aquatic Life
The available data for phthalate
esters indicate that acute toxicity to
saltwater aquatic life occurs at
concentrations as low as 2944 fig/1 and
would occur at lower concentrations
among species that are more sensitive
than those tested. No data are available
concerning the chronic toxicity of
phthalate esters to sensitive saltwater
aquatic life but toxicity to one species of
algae occurs at concentrations as low as
Human Health
For the protection of human health
from the toxic properties of dimethyl-
phthalate ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 313 mg/1.
For the protection of human health
from the toxic properties of dimethyl-
phthalate ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 2.9 g/1.
For the protection of human health
from the toxic properties of diethyl-
phthalate ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 350 mg/1.
For the protection of human-health
from the toxic properties of diethyl-
phthalate ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 1.8 g/1.
For the protection of human health
from the toxic properties of dibutyl-
phthalate ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 34 mg/1.
For the protection of human health
from the toxic properties of dibutyl-
phthalate ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 154 mg/1.
For the protection of human health
from the toxic properties of di-2-
ethylhexyl-phthalate ingested through
water and contaminated aquatic
organisms, the ambient water criterion
is determined to be 15 mg/L
For the protection of human health
from the toxic properties of di-2-
ethylhexyl-phthalate ingested through
contaminated aquatic organisms alone,
the ambient water criterion is
determined to be 50 mg/1.
Polychlorinated Biphenyls
Fresh water A qua tic Life
For polychlorinated biphenyls the
criterion to protect freshwater aquatic
life as derived using the Guidelines is
0.014 fig/1 as a 24-hour average. The
available data indicate that acute
toxicity to freshwater aquatic life
probably will only occur at
concentrations above 2.0 fig/1 and that
the 24-hour average should provide
adequate protection against acute
toxicity.
Saltwater Aquatic Live
For po'ychlorinated biphenyls the
criterion to protect saltwater aquatic life
as derived using the Guidelines is 0.030
jjg/1 as a 24-hour average. The available
data indicate that acute toxicity to
saltwater aquatic life probably will only
occur at concentrations above 10 fig/1
and that the 24-hour average should
provide adequate protection against
acute toxicity.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure -of PCBs through
ingestion of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"', 10~*. and 10"'. The
corresponding criteria are .79 ng/1,0.79
ng/1, and .0079 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are .79 ng/1, .079 ng/1, and .0079
ng/1. respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Polynuclear Aromatic Hydrocarbons
(PAHs)
Freshwater Aquatic Life
The limited freshwater data base
available for polynuclear aromatic
hydrocarbons, mostly from short-term
bloconcentration studies with two
compounds, does not permit a statement
concerning acute or chronic toxicity.
Saltwater Aquatic Life
The available data for polynuclear
aromatic hydrocarbons indicate that
acute toxicity to saltwater aquatic life
occurs at concentrations as low as 300
ug/1 and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of polynuclear aromatic
hydrocarbons to sensitive saltwater
aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of PAHs through
ingestion of contaminated water and
contaminated aquatic organisms, the
ambient water concentration should be
zero based on the non-threshold
assumption for this chemical. However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10"s. 10'6. and 10"'. The
corresponding criteria are 28 ng/1, 2.8
ng/1, and .28 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 311 ng/1. 31.1 ng/1, and 3.11
ng/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Selenium
Freshwater Aquatic Life
For total recoverable inorganic
selenite the criterion to protect
freshwater aquatic life as derived using
the Guidelines is 35 fig/1 as a 24-hour
average and the concentration should
not exceed 260 pg/1 at any time.
The available data for inorganic
selenate indicate that acute toxicity to
freshwater aquatic life occurs at
concentrations as low as 760 pig/1 and
would occur at lower concentrations
among species that are more sensitive
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Federal Register / Vol. 45. No. 231 / Friday. November 2B. 1980 / Notices
than those tested. No data are available
concerning the chronic toxicity of
inorganic selenate to sensitive
freshwater aquatic life.
Saltwater Aquatic Life
For total recoverable inorganic
selenlte the criterion to protect saltwater
aquatic life as derived using the
Guidelines is 54 Mg/1 *»» « 24-hour
average and the concentration should
not exceed 410 jtg/1 at any time. .
No data are available concerning the
toxicity of inorganic selenate to
saltwater aquatic life.
Human Health
The ambient water quality criterion
for selenium is recommended to be
identical to the existing drinking .water
standard which is 10 fig/1. Analysis of
the toxic effects data resulted in a
calculated level which is protective of
human health against the Ingestion of
contaminated water and contaminated
aquatic organisms. The calculated value
Is comparable to the present standard.
For this reason a selective criterion
based on exposure solely from
consumption of 6.5 grams of aquatic
organisms was not derived.
Silver
Freshwater Aquatic Life
For freshwater aquatic life the
concentration (in jig/1) of total
recoverable silver should not exceed the
numerical value given by "e[1.72(ln
(hardness}-6.52}]" at any time. For
example, at hardnesses of 50,100,200
rng/1 as CaCOi the concentration of
total recoverable silver should not
exceed 1.2,4.1, and 13 jig/1, respectively,
at any time. The available data indicate
that chronic toxicity to freshwater
aquatic life may occur at concentrations
as low as 0.12 fig/1.
Saltwater Aquatic Life
For saltwater aquatic life the
concentration of total recoverable silver
should not exceed 2.3 fig/1 at any time.
No data are available concerning the
chronic toxicity of silver to sensitive
saltwater aquatic life.
Human Health
The ambient water quality criterion
for silver is recommended to be
identical to the existing drinking water
standard which is SO jtg/1. Analysis of
the toxic effects data resulted in a
calculated level which is protective of
human health against the ingeation of
contaminated water and contaminated
aqua lie organisms. The calculated value
is comparable to the present standard.
For this reason a selective criterion
based on exposure solely from
consumption of 6.5 grams of aquatic
organisms was not derived,
Tetrachloroethylene
Freshwater Aquatic Life
The available data for
tetrachloroethylene Indicate that acute
and chronic toxicity to freshwater
aquatic life occur at concentrations as
low as 5,280 and 840 fig/1, respectively.
and would occur at lower
concentrations among species that are
more sensitive than those tested.
Saltwater Aquatic Life
The available data for
tetrachloroethylene indicate that acute
and chronic toxicity to saltwater aquatic
life.occur at concentrations low as
10,200 and 450 fig/1, respectively, and
would occur at lower concentrations .
among species that are more sensitive
than those tested.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of
tetrachloroethylene through ingestion of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime ore estimated at 10~*. 10~*,
and 10~T. The corresponding criteria are
8 fig/1, .8 jig/1, and .08 fig/1, respectively.
If the above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 88.5 fig/1,8.85 fig/1, and ,88
fig/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Thallium
Freshwater Aquatic Life
The available data for thallium
indicate that acute and chronic toxicity
to freshwater aquatic life occur at
concentrations as low as 1,400 and 40
ug/1, respectively, and would occur at
lower concentrations among species
that are more sensitive than those •
tested. Toxicity to one species of fish
occurs at concentrations as low as 20
fig/1 after 2,600 hours of exposure.
Saltwater Aquatic Life
The available data for thallium
indicate that acute toxicitv to saltwater
aquatic life occurs at concentrations as
low as 2,130 fig/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available Concerning
the chronic toxicity of thallium to
sensitive saltwater aquatic life.
Human Health
For the protection of human health
from the toxic properties of thallium
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 13 fig/1-
For the protection of human health
from the toxic properties of thallium
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 4B fig/1.
Toluene
Freshwater Aquatic Life
The available data for toluene
indicate that acute toxicity to freshwater
aquatic life occurs at concentrations as
low as 17.500 fig/1 and would occur at
lower concentrations among species
that are more sensitive than those
tested. No data are available concerning
the chronic toxicity of toluene to
sensitive freshwater aquatic life.
Saltwater Aquatic Life
The available data for toluene
indicate that acute and chronic toxicity
to saltwater aquatic life occur at
concentrations as low as 6,300 and 5,000
fig/1, respectively, and would occur at
lower concentrations among species
that are more sensitive than those
tested.
Human Health
For the protection of human health
from the toxic properties of toluene
ingested through water and
contaminated aquatic organisms, the
ambient water criterion is determined to
be 14.3 mg/1.
For the protection of human health
from the toxic properties of toluene
ingested through contaminated aquatic
organisms alone, the ambient water
criterion is determined to be 424 mg/1.
Toxaphene
Freshwater Aquatic Life
For toxaphene the criterion to protect
freshwater aquatic life as derived using
the Guidelines is 0.013 fig/1 as a 24-hour
average and the concentration should
not exceed 1.6 ftg/1 at any time.
Saltwater A guatic Life
For saltwater aquatic life the
concentration of toxaphene should not
exceed 0.070 ftg/1 at any time. No data
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Federal Register / Vol. 45. No. 231 / Friday, November 28. i960 / Notices
79341
are available concerning the chronic
tcxicity of toxaphone to sensitive
saltwater aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of toxaphene
through tngesHon of contaminated water
dnd contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result In Incremental increase of
cancer risk over the lifetime are
estimated at lO"8, W*. and 10"*. The
corresponding criteria are 7.1 ng/1. .71
r.g/L and JO/7 ng/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 7.3 ng/1, .73 ng/1, and IS! ng/1,
respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Trichloroethylene
Freshwater Aquatic Life
The available data for
trlchloroethylene Indicate that acute
toxicity to freshwater aquatic life occurs
at concentrations as low as 45,000 jig/1
and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of trichloroethylene to
sensitive freshwater aquatic life but
adverse behavioral effects occurs to one
species at concentrations as low as
21,900 tig/I.
Saltwater Aquatic Life
The available data for
trichloroethylene indicate that acute
toxicity to salrwater'aquatic life occurs'
at concentrations as low as 2,000 pg/1
and would occur at lower
concentrations among species that are
more sensitive than those tested. No
data are available concerning the
chronic toxicity of trichloroethylene to
sensitive saltwater aquatic life.
Human Health
For the maximum protection of human
health from the potential carcinogenic
effects due to exposure of
trichloroethylene through ingeation of
contaminated water and contaminated
aquatic organisms, the ambient water
concentration should be zero based on
the non-threshold assumption for this
chemical. However, zero level may not
be attainable at the present time.
Therefore, the levels which may result in
incremental increase of cancer risk over
the lifetime are estimated at 10"*, 10"«,
and 10~T. The corresponding criteria are
27 jig/L 2.7 Mg/1. and .27 jig/1,
respectively. If the above estimates are
made for consumption of aquatic
organisms only, excluding consumption
of water, the levels are 807 jtg/1, 80.7
fig/1, and 8.07 jig/l respectively. Other
concentrations representing different
risk levels may be calculated by use of
the Guidelines. The risk estimate range
is presented for information purposes
and does not represent an Agency
Judgment on an "acceptable" risk level.
Vinyl Chloride
Freshwater Aquatic Life
No freshwater organisms have been
tested with vinyl chloride and no
statement can be made concerning acute
or chronic toxicity.
Saltwater Aquatic Life
No saltwater organisms have been
tested with vinyl chloride and no
statement can be made concerning acute
or chronic toxicity.
Human Health
For the maximum protection of human
"health from the potential carcinogenic
effects due to exposure of vinyl chloride
through ingestion of contaminated water
and contaminated aquatic organisms,
the ambient water concentration should
be zero based on the non-threshold
assumption for this chemical However,
zero level may not be attainable at the
present time. Therefore, the levels which
may result in incremental increase of
cancer risk over the lifetime are
estimated at 10~*, 10"B. and «rT. The
corresponding criteria are 20 jig/1, 2.0
jig/1, and ,2 jig/1, respectively. If the
above estimates are made for
consumption of aquatic organisms only,
excluding consumption of water, the
levels are 5,248 ug/1,525 MS/1, and 52.5
fig/1, respectively. Other concentrations
representing different risk levels may be
calculated by use of the Guidelines. The
risk estimate range is presented for
information purposes and does not
represent an Agency judgment on an
"acceptable" risk level.
Zinc
Freshwater Aquatic Life
For total recoverable zinc the criterion
to protect freshwater aquatic life as
derived using the Guidelines is 47 jig/1
as a 24-hour average and the
concentration (in u.g/1] should not
exceed the numerical value given by
e
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79342
Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
necessarily all of the species all of the
time. Aquatic communities can tolerate
some stress and occasional adverse
effects on a few species, and so total
protection of all of the species all of the
time is not necessary. Rather, the
Guidelines attempt to provide a
reasonable and adequate amount of
protection with only a small possibility
of considerable overprotection or
underprotection. Within these
constraints, it seems appropriate to err
on the side of overprotection.
The numerical aquatic life criteria
derived using the Guidelines are
expressed as two numbers, rather than
the traditional one number, so that the
criteria can more accurately reflect
lexicological and practical realities. The
combination of both a maximum value
and a 24-hour average value is designed
to provide adequate protection of
aquatic life and its uses from acute and
chronic toxiclty to animals, toxicity to
plants and bioconcentration by aquatic
organisms without being as restrictive
as a one-number criterion would have to
be to provide the same amout of
protection. The only way to assure the
same degree of protection with a one-
number criterion would be to use the 24-
hour average as a concentration that is
not to be exceeded at any time in any
place.
The two-number criterion is intended
to identify an average pollutant
concentration which will produce a
water qualtly generally suited to the
maintenance of aquatic life and its uses
while restricting the extent and duration
of excursions over the average so that
the total exposure will not cause
unacceptable adverse effects. Merely
specifying an average value over a time
period is insufficient, unless the period
of time is rather short, because of
concentration higher than the average
value can kill or cause substantial
damage in short periods. Furthermore,
for some substances the effect of
intermittent high exposures is
cumulative. It is therefore necessary to
place an upper limit on pollutant
concentrations to which aquatic
organisms might be exposed, especially
when the maximum value is not much
higher than the average value. For some
substances the maximum may be so
much higher than the 24-hour average
that in any real-world situation the
maximum will never be reached if the
24-hour average is achieved. In such
cases the 24-hour average will be
limiting and the maximum will have no
practical significance, except to indicate
that elevated concentrations are
acceptable as long as the 24-hour
average is achieved.
These Guidelines have been
developed on the assumption that the
results of laboratory tests are generally
useful for predicting what will happen in
field situations. The resulting criteria are
meant to apply to most bodies of water
in the United States, except for the
Great Salt Lake. All aquatic organisms
and their common uses are meant to be
considered, but not necessarily
protected, if relevant data are available,
with at least one specific exception. This
exception is the accumulation of
residues of organic compounds in the
siscowet subspecies of lake trout which
occurs in Lake Superior and contains up
to 67!5 fat in the fillets (Thurston, C.E..
1962, Physical Characteristics and
Chemical Composition of Two
Subspecies of Lake Trout, J. Fish. Res.
Bd. Canada 19:39-44). Neither siscowet
nor organisms in the Great Salt Lake are
intentionally protected by these
Guidelines because both may be too
atypical.
. With appropriate modifications these
Guidelines can be used to derive criteria
for any specified geographical area,
body of water (such as the Great Salt
Lake), or group of similar bodies of
water. Thus With appropriate
modifications the Guidelines can be
used to derive national, state, or local '
criteria if adequate information is
available concerning the effects of the
substance of concern on appropriate
species and their uses. However, the
basic concepts described in the
Guidelines should be modified only
when sound scientific evidence
indicates that a criterion produced using
the Guidelines would probably
significantly overprotect or underprotect
the presence or uses of aquatic life.
Criteria produced by these Guidelines
are not enforceable numbers. They may
be used in developing enforceable
numbers, such as water quality
standards and effluent standards.
However, the development of standards
may take into account additional factors
such as social, legal, economic, and
hydrologies! considerations, the
environmental and analytical chemistry
of the substance, the extrapolation from
laboratory data to field situations, and
the relationship between the species for
which data are available and the
species which are to be protected.
Because fresh water and salt water
(including both estuarine and marine
waters) have basically different
chemical compositions and because
freshwater and saltwater species rarely
inhabit the same water simultaneously,
separate criteria should be derived for
these two kinds of waters. However, for
some substances sufficient data may not
be available to allow derivation of one
or both of these criteria using the
Guidelines.
These Guidelines are mean* to be
used after a decision is made that a
criterion is needed for a substance. The
Guidelines do not address the rationale
for making that decision. If the potential
for adverse effects on aquatic life and
its uses are part of the basis for deciding
whether or not a criterion is needed for
a substance, these Guidelines may be
helpful in the collection and
interpretation of relevant data.
/. Define the Substance for Which the
Criterion Is To Be Derived
A. Each separate chemical which
would not ionize significantly in most
natural bodies of water should usually
be considered a separate substance,
except possibly for structurally similar
organic compounds that only differ in
the number and location of atoms of a
specific halogen, and only exist in large
quantities as commercial mixtures of the
various compounds, and apparently
have similar chemical, biological, and
toxicological properties.
B. For chemicals, which would ionize
significantly in most natural bodies of
water, such as inorganic salts, organic
acids and phenols, all forms that would
be in chemical equilibrium should
usually be considered one substance.
For metals, each different valence and
each different covalently bonded
organometallic compound should
usually be considered a separate
substance.
C. The definition of the substance may
also need to take into account the
analytical chemistry and fate of the
substance.
//. Collect and Review A vailable Data
A. Collect all available data on the
substance concerning (1) toxicity to, and
bioaccumulation by. aquatic animals
and plants, (2) FDA action levels, and
(3) chronic feeding studies with wildlife.
B. Discard all data that are not
available in hard copy (publication,
manuscript, letter, memorandum, etc.)
with enough supporting information to
indicate that acceptable test procedures
were used and that the results are
reliable. Do not assume that all
published data are acceptable.
C. Discard questionable data. For
example, discard data from tests for
which no control treatment existed, In
which too many organisms in the control
treatment died or showed signs of stress
or disease, or in which distilled or
deionized water was used as the
dilution water for aquatic organisms.
Discard data on formulated mixtures
and emulsifiable concentrates of the
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Federal Register / .Vol. 45. No. 231 / Friday. November 28. 1980 / Notices 79343
substance of concern, but not
necessarily data on technical grade
material.
D. Do not use data obtained using;
1. Brine shrimp, because they usually
only occur naturally in water with
salinity greater than 35 g/kg.
2. Species that do not nave
reproducing wild populations resident
in—but not necessarily native to—North
America. Resident North American
species of fishes are defined as those
listed In "A List of Common and
Scientific Names of Fishes from the
United States and Canada", 3rd ed.,
Special Publication No. 6, American
Fisheries Society, Washington, D.C.,
1970. Data obtained with non-resident
species can be used to Indicate
relationships and possible problem
areas, but cannot be used in the
derivation of criteria.
9, Organisms that were previously
exposed to significant concentrations of
the test material or other pollutants.
///. Minimum Data Base
A, A minimum amount of data should
be available to help ensure that each of
the four major kinds of possible adverse
effects receives some consideration.
Results of acute and chronic toxicity
tests with a reasonable number and
variety of aquatic animals are necessary
so that data available for tested species
can be considered a useful indication of
the sensitivities of the numerous
untested species. The requlurements
concerning toxicity to aquatic plants are
less stringent because procedures for
conducting tests with plants are not as
well developed and the interpretation of
the results is more questionable. Data
concerning bioconcentration by aquatic
organisms can only be used if other
relevant data are available.
B. To derive a criterion for freshwater
aquatic life, the following should be
available:
1. Acute tests (see Section IV) with
freshwater animals in at least eight
different families provided that of the
eight species;
—at least one is a salmonid fish
—at least one is a non-sabnonid fish
—at least one is a planktonic crustacean
—at least one Is a benthic crustacean
—at least one is a benlhlc insect
—at least one of the benthic species is a
detritivore
2, Acute-chronic ratios (see Section
VI] for at least three species of aquatic
animals provided that of the three
species:
—at least one is a fish
—at least one is an invertebrate
—at least one is a freshwater species
(the other two may be saltwater
species]
3. At least one test with a freshwater
alga or a chronic test with a freshwater
vascular plant (see Section VIII). If
plants are among the aquatic organisms
that are most sensitive to the substance,
tests with more than one species should
be available.
4. At least one acceptable
bioconcentration factor determined with
an aquatic animal species, if a maximum
permissible tissue concentration Is
available (see Section DC).
C. To derive a criterion for saltwater
aquatic life, the following should be
available;
1. Acute tests (see Section IV) with
saltwater animals in at least eight
different families provided that of the
eight-species:
—at least two different fish families are
included
—at least five different invertebrate
families are included
—either the Mysldae or Penaeidae
family or both are included
—at least one of the Invertebrate
families is in a phylum other than
Arthropoda
2. Acute-chronic ratios (see Section
VI} for at least three species of aquatic
animals provided that of the three
species:
—at least one is a fish
—at least one is an invertebrate
—at least one is a saltwater species (the
other two may be freshwater species]
3. At least one test with a saltwater
alga or a chronic test with a saltwater
vascular plant (see Section VIII]. If
plants are among the aquatic organisms
most sensitive to the substance, tests
with more than one species should be
available.
4. At least one acceptable
bioconcentration factor determined with
an aquatic animal species, if a maximum
permissible tissue concentration Is
available (see Section DC).
D. If all the requirements of the
minimum data base are met, a criterion
can usually be derived, except in special
cases. For example, a criterion might not
be possible if the. acute-chronic ratios
vary greatly with no apparent pattern.
Also, if a criterion is to be related to a
water quality characteristic, (see
Sections V and VII), more data will be
necessary.
Similarly, if the minimum data
requirements are not satisfied, generally
a criterion should not be derived except
in special cases. One such special case
would be when less than the minimum
amount of acute and chronic data are
available, but the available data clearly
indicate that the Final Residue Value
would be substantially lower then either
the Final Chronic Value or the Final
Plant Value.
IV. Final Acute Value
A. Appropriate measures of the acute
(short-term) toxicity of the substance to
various species of aquatic animals are
used to calculate the Final Acute Value.
If acute values are available for fewer
than twenty species, the Final Acute
Value probably should be lower than
the lowest value. On the other hand, if
acute values are available for more than
twenty species, the Final Acute Value
probably should be higher than the
lowest value, unless the most sensitive
species is an important one. Although
the procedure used to calculate the Final
Acute Value has some limitations. It
apparently Is the best of the procedures
currently available.
B. Acute toxicity tests should be
conducted using procedures such as
those described In:
ASTM Standard E 729-80, Practice for
Conducting Acute Toxicity Tests with
Fishes, Macroinvertebrates, and
Amphibians. American Society for
Testing and Materials, 1916 Race Street,
Philadelphia, PA 18103.
ASTM Standard 1724-40, Practice for
Conducting Static Acute Toxicity Tests
with Larvae of Four Species of Bivalve
Molluscs. American Society for Testing
and Materials. 1916 Race Street,
Philadelphia. PA 19103.
C. Results of acute tests in which food
was added to the test solutions should
not be used, because this may
unnecessarily affect the results of the
test.
D. Results of acute tests conducted
with embryos should not be used (but
see Section FV.E.2), because this is often
an Insensitive life stage.
E. Acute values should be based on
endpoints and lengths of exposure
appropriate to the life stage of the
species tested. Therefore, only the
following kinds of data on acute toxicity
. to aquatic animals should be used:
1.48-hr EC50 values based on
Immobilization and 48-hr LC50 values
for flrst-instar (less than 24 hours old)
daphnlds and other cladocerans, and
second- or thlrd-instar midge larvae.
2.48- to 96-hr ECSO values based on
Incomplete shell development and 48- to
96-hr LC50 values for embryos and
larvae of barnacles, bivalve molluscs
(clams, mussels, oysters, and scallops],
sea urchins, lobsters, crabs, shrimps,
and abalones.
3.96-hr ECSO values based on
decreased shell deposition for oysters.
4.96-hr ECSO values on
immobilization or loss of equilibrium or
both and 96-hr LCSO values for aquatic
animals, except for cladocerans, midges,
and animals whose behavior or
physiology allows .them to avoid
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79344
Federal Register / Vol. 45. No. 231 / Friday, November 28. 1980 / Notices
exposure to toxicant or for whom the
acute adverse effect of the exposure
cannot be adequately measured. Such
freshwater and saltwater animals
include air-breathing molluscs, unionid
clams, operculate snails, and bivalve
molluscs, except for some species that
cannot "close up" and thus prevent
exposure to toxicant, such as the bay
scallop (Aigppecten irradians).
V. For the 'use of LC50 or EC5Q values
for durations shorter and longer than
those listed above, see Section X
G. If the acute toxic! ty of the
substance to aquatic animals has been
shown to be related to a water quality
characteristic such as hardness for
freshwater organisms or salinity for
saltwater organisms, a Final Acute
Equation should be derived based on
that water quality characteristic. Go to
Section V.
H. If the acute toxicity of the
substance has not been adequately
shown to be related to a water quality
characteristic, for each species tor
which at least one acute value is
available, calculate the geometric mean
of the results of all flow-through tests in
which the toxicant concentrations were
measured. For a species for which no
such result is available, calculate the
geometric mean of all available acute
values, i.e., results of flow-through tests
in which the toxicant concentrations
were not measured and results of static
and renewal testa based on initial total
toxicant concentrations.
Not*.—The geometric mean of N numbers
te obtained by taking the N«* root of the
product of N numbers. Alternatively, the
geometric mean can be calculated by adding
the logarithms of the N numbers, dividing the
sum by N, and taking the antilog of the
quotient The geometric mean, of two numbers
con alia be calculated as the square loot of
the product of the two numbers. The
geometric mean of one number is that
number. Either natural (base a) or common
(base 10} logarithms can be used to calculate
geometric means as long as they are used
consistently within each.set of data, Le« the
antilog used must match the logarithm used.
I. Count the number «N of species for
which a species mean acute value is
available.
J. Order the species mean acute
values from low to high. Take the
common logarithms of the N values (log
mean values).
K. The intervals (cell widths) for the
lower cumulative proportion
calculations are 0.11 common log units
apart, starting from the lowest log value.
The value of 0.11 is an estimate of
average precision and was calculated
from replicate species acute values.
L. Starting with the lowest log mean
value, separate the N values into
intervals (or cells) calculated in Step IV,
K.
M. Calculate cumulative proportions
for each non-empty interval by summing
the number of values In the present and
all lower intervals and dividing by N.
These calculations only need to be done
for the first three non-empty intervals
(or cells).
N. Calculate the arithmetic mean of
the log mean values for each of the three
intervals.
O. Using the two interval mean acute
values and cumulative proportions
closest to 0.05, linearly extrapolate or
Interpolate to the O.OS log concentration.
The Final Acute Value is the antilog of
the O.OS concentration. ~
In other words, where
Prop(l) and conc(l] are the cumulative
proportion, and mean log value for the
lowest non-empty interval.
Prop(2) and conc(2) are the cumulative
proportion and mean log value for the
second lowest non-empty interval
A <= Slope of the cumulative proportions
B=The 0.05 log value
Them
A=[0.05-Prop(l]]/[Prop{2)-Prop(l]]
B=conc(l)+A |conc(2)-conc(l)J
Final Acute Value=10s
P. If for an important species, such as
a recreationally or commercially
important species, the geometric mean
of the acute values from flow-through
tests m which the toxicant
concentrations were measured is lower
than the Final Acute Value, then that
geometric mean should be used as the
Final Acute Value.
Q. Go to Section VL
V, Final Acute Equation
A. When enough data are available to
show that acute toxicity to two ot more
specie&ls similarly affected by a water
quality characteristic, this effect can be
taken into account as described below.
Pooled regression analysis should
produce similar results, although data
available for individual species would
be weighted differently.
B. For each species for which
comparable acute toxicity values are
available at two or more different
values of a water quality characteristic
which apparently affects toxicity,
perform a least squares regression of the
natural logarithms of the acute toxicity
values on the natural logarithms of the
values of the water quality
characteristic. (Natural logarithms
[logarithms to the base e, denoted as In]
are used herein merely because they are
easier to use on some hand calculators
and computers than common logarithms
[logarithms to the base 10]. Consistent
use of either will produce the same
result.) No transformation or a different
transformation may be used'if it fits the
data better, but appropriate changes will
be necessary throughout this section.
C. Determine whether or not each
acute slope Is meaningful, taking into
account the range and number of values
of the water quality characteristic
tested. For example, a slope based on
four data points may be of limited value
if it is based only on data for a narrow
range of values of the water quality
characteristic. On the other hand, a
slope based on only two data points
may be meaningful if it is consistent
with other information and if the two
points cover a broad enough range of •
the water quality characteristic. If
meaningful slopes are not available for
at least two species or if the available
slopes are not similar, return to Section
IV. H.. using the results of tests
conducted under conditions-and in
•water similar to those commonly used
for toxicity tests with the species.
D. Calculate the mean acute slope [V)
as the arithmetic average of all the
meaningful acute slopes for individual
species.
E. For each species calculate the
geometric mean (W) of the acute toxicity
values and the geometric mean (XJ of
the related values of the water quality
characteristic,
F. For each species calculate the
logarithmic intercept (Y) using the
equation: Y=ta W-V(ln X).
G. For each species calculate the
species mean acute intercept as the
antilog of Y.
H. Obtain the Final Acute Intercept by
using the procedure described in Section
IV. I-O, except Insert "Intercept" for
"Value".
I. If for an important species, such as a
recreationally or commercially
important species, the intercept
calculated only from results of flow-
through tests in which the toxicant
concentrations were measured is lower
than the Final Acute Intercept, then that
intercept should be used as the Final
Acute Intercept.
J. The Final Acute Equation Is written
as e'*1""'"1" i""" eh««euii«u«a+i» »t where
V=mean acute slope and Z=Final
Acute Intercept
VI Final Chronic Value
A. The Final Chronic Value can be
calculated in the same manner as the
Final Acute Value or by dividing the
Final Acute Value by the Final Acute*
Chronic Ratio, depending on the data
available. In some cases it will not be
possible to calculate a Final Chronic
Value.
B. Use only the results of flow-through
(except renewal is acceptable for
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1880 / Notices 79315
daphnids) chronic tests in which the
concentrations of toxicant in the test
solutions were measured.
C. Do not use the results of any
chronic test In which survival, growth,
or reproduction among the controls was
unacceptably low.
D. Chronic values should be based on
endpoints and lengths of exposure
appropriate to the species. Therefore,
only the results of the following kinds of
chronic toxlclty tests should be used:
1. Life-cycle toxicity tests consisting
of exposures of each of several groups
of individuals of a species to a different
concentration of the toxicant throughout
a life cycle. To ensure that-all life stages
and life processes are exposed, the test
should begin with embryos or newly
hatched young less than 48 hours old
(iess than 24 hours old for daphnids],
continue through maturation and
reproduction, and with fish should end
not less than 24 days (80 days for
salmonids) after the hatching of the next
generation. For fish, data should be
obtained and analyzed on survival and
growth of adults arid young, maturation
of males and females, embryos spawned
per female, embryo viability (salmonids
only) and hatchability. For daphnids,
data should be obtained and analyzed
on survival and young per female.
2. Partial life-cycle toxidty tests
consisting of exposures of each of
several groups of individuals of a
species of fish to a different
concentration of the toxicant through
uost portions of a life cycle. Partial life-
:ycle tests are conducted with fish
species that require more than a year to
each sexual maturity, so that the test
:an be completed In less than 15
aonths, but still expose all major life
•tages to the toxicant. Exposure to the
oxicant begins with immature Juveniles
it least 2 months prior to active gonad
levelopment, continues through
naturation and reproduction, and ends
tot less than 24 days (90 days for
almonids) after the hatching of the next
eneration. Data should be obtained and
nalyzed on survival and growth of
dults and young, maturation of males
nd females, embryos spawned per
•male, embryo viability (salmonids
nly] and hatchability.
3. Early-life-stage toxicity tests
insisting of 28- to 32-days (60 days
Dst-hatch for salmonids] exposures of
ie early life stages of a species of fish
om shortly after fertilization through
nbryonic, larval, and early juvenile
jvelopment. Data should be obtained
id analyzed on survival and growth.
E. Do not use the results of an tarly-
s-stage test if results of a life-cycle or
irtial life-cycle test with the same
, -ecies are available.
F, A chronic value is obtained by
calculating the geometric mean of the
lower and upper chronic limits from a
chronic test. A lower chronic limit is the
highest tested concentration (1) in an
acceptable chronic test, [2] which did
not cause the occurrence (which was
statistically significantly different from
the control at p-0.05] of a specified
adverse effect, and (3) below which no
tested concentration caused such an
occurrence. An upper chronic limit is the
lowest tested concentration (I) in an
acceptable chronic test, (2] which did
cause the occurrence (which was
statistically significantly different from
the control at p=0.05) of a specified
adverse effect and (3) above which all
tested concentrations caused such an
occurrence.
Note.—Various authors have used a
variety of terms and definitions to Interpret
the results of chronic tests, so reported
results should be reviewed carefully.
G. If the chronic toxicity of the
substance to aquatic animals has been
adequately shown to be related to a
water quality characteristic such as
hardness for freshwater organisms or
salinity for saltwater organisms, a Final
Chronic Equation should be derived
based on that water quality
characteristic. Go to Section VII.
H. If chronic values are available for
eight species as described In Section 01.
B.I or m. C.I, a species mean .chronic
value should be calculated for each
species for which at least one chronic
value is available by calculating the
geometric mean of all the chronic values
for the species. The Final Chronic Value
should then be obtained using the
procedures described in Section IV. I-O.
Then go to Section VI. M.
I. For each chronic value for which at
least one appropriate acute value is
available, calculate an acute-chronic
ratio, using for the numerator the
arithmetic average of the results of alJ
standard flow-through acute tests in
which the concentrations were
measured and which are from the same
study as the chronic test. If such an
acute test is not available, use for the
numerator the results of a standard
acute test performed at the same
laboratory with the same species,
toxicant and dilution water. If no such
acute test is available, use the species
mean acute value for the numerator.
Note.—If the acute toxlclty or chronic
toxicity or both of the substance have been
adequately shown to be related to a water
quality characteristic, the numerator and the
denominator must be based on tests
performed in the same water.
J. For each species, calcuate the
species mean acute-chronic ratio as the
geometric mean of all the acute-chronic
ratios available for that species.
K. For some substances the species
mean acute-chronic ratio seems to be
the same for all species, but for other
substances the ratio seems to increase
as the species mean acute value
increases. Thus the Final Acute-Chronic
Ratio can be obtained in two ways,
depending on the data available.
1, If no major trend is apparent and
the acute-chronic ratios for a number of
species are within a factor of ten, the
final Acute-Chronic Ratio should be
calculated as, the geometric mean of all
the species mean acute-chronic ratios
available for both freshwater and
saltwater species.
2. If the species mean acute-chronic
ratio seems to increase as the species
mean acute value increases, the value of
the acute-chronic ratio for species
whose acute values are close to the
Final Acute Value should be chosen as
the Final Acute-Chronic Ratio.
L Calculate the Final Chronic Value
by dividing the Final Acute Value by the
Final Acute-Chronic Ratio.
M. If the species mean chronic value
of an important species, such as a
commercially or recreationally
important species, is lower than the
Final Chronic Value, then that species
mean chronic value should be used as
the Final Chronic Value.
N. Go to Section VIII.
VII. Final Chronic Equation
. A. For each species for which
comparable chronic toxicity values are
available at two or more different
values of a water quality characteristic
which apparently affects chronic
toxicity, perform a least squares
regression of the natural-logarithms of
the chronic toxidty values on the
natural logarithms of the water quality
characteristic values. No transformation
or a different transformation may be
used if it fits the data better, but
appropriate changes will be necessary
'throughout this section. It is probably
preferable, but not necessary,-to use the
same transformation that was used with
the acute values in Section V,
B. Determine whether or not each
chronic slope is meaningful, taking into
account the range and number of values
of the water quality characteristic
tested. For example, a slope based on
four data points may be of limited value
if it is based only on data for a narrow
range of values of the water quality
characteristic. On the other hand, a .
slope based on only two data points
may be meaningful if it is consistent
with other information and if'the two
points cover a broad enough range of
the water quality characteristic. If a
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79348
Federal Register / Vol. 45, No. 231 / Friday, November 28. 1980 / Notices
meaningful chronic slope is not
available for at least one species, return
to Section VI. H.
C. Calculate the mean chronic slope
(L) as the arithmetic average of all the
meaningful chronic slopes for individual
species.
D. For each species calculate the
geometric mean (M) of the toxicity
values and the geometric mean (P) of the
related values of the water quality
characteristic.
E. For each species calculate the
logarithmic intercept (Q) using the
equation: Q=lnM-L(ln P).*
F. For each species calculate a species
mean chronic intercept as the antilog of
Q. -
G. Obtain the Final Chronic Intercept
by using the procedure described in
Section TV. I-O, except insert
"Intercept" for "Value".
H. If the species mean chronic
intercept of an important species, such
as a commercially or recreationally
important species. Is lower than the
Final Chronic Intercept then that
species mean chronic intercept should
be used as the Final,Chronic Intercept.
I. The Final Chronic Equation is
written as e Q&*t**t*T.n*utr d»>«Mri«uc>|+tn
B), where L=mean chronic slope and
R= Final Chronic Intercept
VIII. Final Plant Value
A. Appropriate measures of the
toxicity of the substance to aquatic
plants are used to compare the relative
sensitivities of aquatic plants and
animals.
B. A value is a concentration which
decreased growth (as measured by dry
weight chlorophyll etc.) in a 96-hr or
longer test with an alga or in a chronic
test with, an aquatic vascular plant
C. Obtain the Final Plant Value by
selecting the lowest plant value from a
test in which the toxicant concentrations
were measured.
IX, Final Residue Value
A. The Final Residue Value is derived
in order to (1] prevent commercially or
recreationally important aquatic
organisms from exceeding relevant FDA
action levels and (2) protect wildlife,
including fishes and birds, that eat
aquatic organisms from demonstrated
adverse effects. A residue value ia
calculated by dividing a maximum
permissible tissue concentration by an
appropriate bioconcentration factor
(BCF). where the BCF is the quotient of
the concentration of a substance in all
or part of an aquatic organism divided
by the concentration in water to which
the organism has been exposed. A
maximum permissible tissue
concentration is either (1) an action
level from the FDA Administrative
Guidelines Manual for fish oil or for the
edible portion of fish or shellfish, or [2] a
maximum acceptable dietary intake
based on observations on survival,
growth or reproduction in a chronic
wildlife feeding study. If no maximum
permissible tissue concentration is
available, go to Section X because no
Final Residue Value can be derived.
B. L A BCF determined in a
laboratory test should be used only if it
was calculated based on measured
concentrations of the substance in the
test solution and was based on an
exposure that continued until either
steady-state or 28-days was reached.
Steady-state is-reached when the BCF
does not change significantly over a
period of time, such as two days or 16
percent of the length of the exposure,
whichever is longer. If a steady-state
BCF is not available for a species, the
available BCF for the longest exposure
over 28 days should be used for that
species.
2. A BCF from a field exposure should
be used only when it is known that the
concentration, of the substance was
reasonably constant for a long enough
period of time over the range of territory
inhabited by the organisms.
3. If BCF values from field exposures
are consistently lower or higher than
those from laboratory exposures, then
only those values from field.exposures
should be used if possible.
4. A BCF should be calculated based
on the concentration of the substance
and its. metabolites, which are
structurally similar and are not much1
more soluble in water than the parent
compound, in appropriate tissue and
should be corrected for the
concentration in the organisms at the
beginning of the test.
5. A BCF value obtained from a
laboratory or field exposure that caused
an observable advene effect on the test
organism may be used only if it is
similar to that obtained with unaffected
organisms at lower concentrations in the
sametesL
6. Whenever a BCF is determined for
a lipid-soluble substance, the percent
lipids should also be determined in the
tissue for which the BCF was calculated.
C. A BCF calculated using dry tissue
weights must be converted to a wet
tissue weight basis by multiplying the
dry weight BCF value by 0.1 for
plankton and by 0.2 for individual
species of fishes and invertebrates.
Note.—The values of 0.2 and 0.1 were
derived from data published in:
McDiffett, W. F., 1870, Ecology 51:875-988.
Bracken. R. W, et aL 1988. J. Wildlife
Management 32:52-75.
Cummins. K. W., et al. 1973. Ecology 54: 338-
345.
Pesticide Analytical Manual. Volume 1, Food
and Drug Administration. 1988. •
Love. R. M.. 1957. In The Physiology of Fishes,
Vol. I. M. E. Brown, ed. Academic Press
New York. p. 411.
Ruttner, F.. 1963. Fundamentals of Limnology.
3rd ed. Trans, by D. G. Frey and F. E. |. Fry.
Univ. of Toronto Press, Toronto.
Some additional values can be found in:
Sculthorpe. C. D., 1987. The Biology of
Aquatic Vascular Plants. Arnold Publishing
Ltd., London.
D. If enough 'pertinent data exist
several residue values can be calculated
by dividing maximum permissible tissue
concentrations by appropriate BCF
values.
1. For each available maximum.
acceptable dietary intake derived from a
chronic feeding study wish wildlife,
including birds and aquatic organisms.
the appropriate BCF is based on the
whole body of aquatic species which
constitute or represent a major portion
of the diet of the tested wildlife species.
2. For an FDA action level, the
appropriate BCF is the highest geometric
mean species BCF for the edible, portion
(muscle for decapods- muscle with or
without skin .for fishes, adductor muscle .
for scallops and total living tissue for
other bivalve molluscs) of a consumed
species. The highest species BCF is used
because FDA action levels are applied
on a specles-by-species basis.
E. For lipJd-soluble substances, it may
be possible to calculate additional
residue values. Because steady-state
BCF values for a lipid-soluble chemical
seem to be proportional to percent lipids
from one tissue to another and from one
species, to another, extrapolations can
be made from tested tissues or species
to untested tissues or species on the
basis of percent lipids.
1. For each BCF for which the percent
lipids is known for the same tissue for
which the BCF was measured, the BCF
should be normalized to a one percent
lipid basis by dividing the BCF by the
percent lipids. This adjustment to a one
percent lipid basis makes all the
measured BCF values comparable
regardless of the species or tissue for
which the BCF was measured.
2. Calculate the geometric mean
normalized BCF. Data for both saltwater
and freshwater species can be used to
determine the mean normalized BCF.
because the normalized BCF seems to
be about the same for both kinds of
organisms.
3. Residue values can then be
calculated by dividing the maximum
permissible tissue concentrations by the
mean normalized BCF and by a percent
lipids value appropriate to the maximum
permissible tissue concentration, i.e..
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1930 / Notices
79347
Residua Value • jnaximua permissible tissue concentration)
(mean normalized BC7)(appropriate percent lipids)
exceeded on the average in a 24-hour
period and one that should not be
exceeded at any time during the 24-hour
period. This two-number criterion is
intended to identify water quality
conditions that should protect aquatic
life and its uses from acute and chronic
adverse effects of both cumulative and
noncumulative substances without being
as restrictive as a one-number criterion
would have to be to provide the same
degree of protection.
B. The maximum concentration is the
Final Acute Value or is obtained from
the Final Acute Equation.
C. The 24-hour average concentration
is obtained from the Final Chronic
Value, the Final Plant Value, and the
Final Residue Value by selecting the
lowest available value, unless other
data (see Section X) from tests in which
the toxicant concentrations were
measured show that a lower value
should be used. If toxicity is related to a
water quality characteristic, the 24-hour
average concentration is obtained from
the Final Chronic Equation, the Final
Plant Value, and the Final Residue
Value by selecting the one that results in
the lowest concentrations in the normal
range of the water quality characteristic,
unless other data (see Section X] from
tests in which the toxicant
concentrations were measured show
that a lower value should be used.
D. The criterion is (the 24-hour
average concentration) as a 24-hour
average and the concentration should
not exceed (the maximum
concentration] at any time.
XII. Review
A. On the basis of all available
pertinent laboratory and field
information, determine if the criterion is
consistent with sound scientific
evidence. If it is not, another criterion,
either higher or lower, should be derived
using appropriate modifications of the
Guidelines.
These Guidelines were written by
Charles E. Stephen, Donald I. Mount,
David ]. Hansen, John H. Gentile, Gary
A. Chapman and William A. Brungs of
the U.S.E.P.A. Environmental Research
Laboratories in Corvallis, Oregon,
Duluth, Minnesota, Gulf Breeze. Florida,
and Narragansett, Rhode Island.
Numerous other people, many of whom
do not work for U.S.E.P.A.. provided
assistance and suggestions.
a. For an FDA action level for fish oil,
the appropriate percent lipids value is
100.
b. For an FDA action level for fish, the
appropriate percent lipids value is 15 for
fr< .water criteria and 16 for saltwater
cr. eria because FDA action levels are
applied on a species-by-species basis to
commonly consumed species. The edible
portion of the freshwater lake trout
averages about IS percent lipids, and
the edible portion of the saltwater
Atlantic herring averages about 16
percent lipids (Sidwell, V. D., et al. 1974
Composition of the Edible Portion of
Raw (Fresh or Frozen] Crustaceans,
Finfish, and Mollusks. L Protein. Fat,
Moisture, Ash, Carbohydrate, Energy
Value, and Cholesterol. Marine Fisheries
Review 36:21-35).
c. Foe a maximum acceptable dietary
intake derived from a chronic feeding
study with wildlife, the appropriate
percent lipids is the percent lipids of an
aquatic species or group of aquatic
species which constitute a major portion
of the diet of the wildlife species.
F. The Final Residue Value is
obtained by selecting the lowest of the
available residue values. It should be
noted that in many cases the Final
Residue Value will not be low enough.
For example, a residue value calculated
from an FDA action level would result in
an average concentration in the edible
portion of a fatty species that is at the
action level On the average half of the
individuals of the species would have
concentrations above the FDA action
level. Also, the results of many chronic
feeding studies are concentrations that
cause adverse effects.
X. Other Data
Pertinent information that could not
be used in earlier sections may be
available concerning adverse effects on
aquatic organisms and their uses. The
most important of these are data on
flavor impairment, reduction in survival,
growth, or reproduction, or any other
adverse effect that has been shown to
be biologically significant. Especially
important are data for species for which
10 other data are available. Data from
Behavioral, micorcosm, field, and
Dhysiological studies may also be
ivailable.
.'/. Criterion
A. The criterion consists of two
oncentrations, one that shquld not be
Appendix C-Guidellnes and
Methodology Used In the Preparation of
Health Effect Assessment Chapters of
the Consent Decree Water Criteria
Documents
/ Objective
The objective of the health effect
assessment chapters of the ambient
water criteria documents is to estimate
ambient water concentrations which do
not represent a significant risk to the
public. These assessments should
constitute a review of all relevant
information on individual chemicals or
chemical classes in order to derive
criteria that represent, in the case of
suspect or proven carcinogens, various
levels of incremental cancer risk, or, in
the case of other pollutants, estimates of
no-effect levels.
Ideally, ambient water quality criteria
should represent levels for compounds
in ambient water that do not pose a
hazard to the human population.
However, in any realistic assessment of
human health hazard, a fundamental
distinction must be made between
absolute safety and the recognition of
some risk. Criteria for absolute safety
would have to be based on detailed
knowledge of dose-response
relationships in humans, including all
sources of chemical exposure, the types
of toxic effects elicited, the existence of
thresholds for the toxic effects, the
significance of toxicant interactions, and
the variances of sensitivities and
exposure levels within the human
population. In practice, such absolute
criteria cannot be established because
of deficiencies in both the available data
and the means of interpreting this
information. Consequently, the
Individual human health effects chapters
propose criteria which minimize or
specify the potential risk of adverse
human effects due to substances in
ambient water. Potential social or
economic costs and benefits are not
considered in the formulation of the
criteria.
II. Types of Criteria
Ambient water quality criteria are
based on three types of biological
endpoints: carcinogenicity, toxicity (i.e.,
all adverse effects other than cancer),
and organoleptlc effects.
For the purpose of deriving ambient
water quality criteria, carcinogenicity is
regarded as a non-threshold
phenomenon. Using this assumption,
"safe" or "no effect" levels for
carcinogens cannot be established'
because even extremely small doses
must be assumed to elicit a finite
increase in the incidence of the
response. Consequently, water quality
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criteria for carcinogens are presented as
a range of pollutant concentrations
associated with corresponding
incremental risks.
For compounds which do not manifest
any apparent carcinogenic effect the
threshold assumption is used in deriving
a criterion. This assumption is based on
the premise that a physiological reserve
capacity exists within the organism
which is thought to be depleted before
clinical disease ensues. Alternatively, it
may be assumed that the rate of damage
will be Insignificant over the life span of
the organism. Thus, ambient water .
quality criteria are derived for non-
carcinogenic chemicals, and presumably
result in no observable-adverse-effect
levels (NOAELs) in the exposed human
population.
In some instances, criteria are based
on organoleptiO'Characteristics, i.e.,
thresholds for taste or odor. Such
criteria are established when
insufficient information is available on
toxicologic effects or when the estimate
of the level of the pollutant in ambient
water based on organoleplic effects is
lower than Ihe level calculated from
toxicologic data. It should be recognized
that criteria based solely on
crvanokptic effects do net necessarily
represent approximations of acceptable
risk levels for human health.
Several ambient water quality criteria
documents deal with classes of
compounds which include chemicals
exhibiting varying degrees of structural
similarity. Because prediction of
biological effects based solely on
structural parameters is difficult, the
derivation of compound-specific criteria
is preferable to'a class criterion. A
compound-specific criterion is defined
as a level derived from data on each
individual subject compound that does '
not represent a significant risk to the
public. For some chemical classes,
however, a compound-specific criterion
cannot be derived for each member of a
class. In such Instances, it is sometimes
justifiable to derive a class criterion in
which available data on one member of
a class may be used to estimate criteria
for other chemicals of the class because
e sufficient data base is not available
for those compounds.
For some chemicals and chemical
classes, the data base was judged to be
insufficient for the derivation of a
criterion. In those cases, deficiencies in
the available Information are detailed.
///. Approach
The human health effects chapters
attempt to summarize all information on
the individual chemicals or classes of
chemicals which might be useful in the
risk assessment process to develop
water quality criteria. Although primary
emphasis is placed on identifying
epidemiologic and toxicologic data,
these assessments typically contain
discussions on four topics: existing
levels of human exposure,
phannacoklnetics, toxic effects, and
criterion formulation.
For all documents, an attempt is made
to include the known relevant
information. Review articles and reports
are often used in the process of data
evaluation and synthesis. Scientific
Judgment is exercised in the review and
evaluation of the data in each document
and in the identification of the adverse
effects against which protective criteria
are sought. la addition, each of these •
documents is reviewed by a peer
committee of scientists familiar with the
specific compound(s). These work
groups evaluate the quality of the
available data, the completeness of the
data summary, and the validity of the
derived criterion.
In the analysis and organization of the
data, an attempt is made to be
consistent with respect to the format
and the application of acceptable
scientific principles. Evaluation
procedures used in the hazard
assessment process follow the principles
outlined by the National Academy of
Sciences in Drinking Water and Health
(1077) and the guidelines of the
Carcinogen Assessment Group of the
U.S. EPA.
A. Exposure
The exposure section of the health
effects chapters reviews known
information on current levels of human
exposure to the individual pollutant
from all sources. Much of the data was
obtained from monitoring studies of air,
water, food, soil, and human or animal
tissue residues. The major purpose of
this section is to provide background
information on the contribution of water
exposure relative to all other sources.
Consequently, the exposure section
includes subsections reviewing different
routes of exposure including water and '
food ingestion, inhalation, and dermal
contact.
Information on exposure can be
valuable in developing and assessing a
water quality criterion. In these
documents exposure from consumption
of contaminated water and
contaminated fish and shellfish products
is used in criterion formulation. Data for
all modes of exposure are useful in
relating total intake to the expected
contribution from contaminated water.
fish, and shellfish. In addition,
information for all routes of exposure,
not limited to drinking water and fish
and shellfish ingestion, can be used to
Justify or assess the feasibility of the
formulation of criteria for ambient
water.
The use of fish consumption a's an
exposure factor requires the
quantitation of pollutant residues in the
edible portions of the ingested species.
Accordingly, bioconcentration factors
(BCFs) are used to relate pollutant
residues in aquatic organisms to the
pollutant concentration in the ambient
waters in which they reside.
To estimate the average per capita
intake of a pollutant due to consumption
of contaminated fish and shellfish the
results of a diet survey were analyzed to
calculate the average consump tion of
' freshwater and-eetuarine fish and
shellfish (U.S. EPA. 1980). A species is
considered to be a consumed freshwater
or estuarine fish and shellfish species if
at some stage in its life cycle, it is
harvested from fresh or estuarine water
for human consumption in significant
quantities (Stephan, 1980].
Three different procedures are used to
estimate the weighted average BCF
depending upon the lipid solubility of
the chemical and the availability of
bioconcentration data.
For lipid-soluble compounds, the
average BCF is calculated from the
weighted average percent lipids in the
edible portions of consumed freshwater
and estuarine fish and shellfish which
was calculated from data on
consumption of each species and its
corresponding percent lipids to be 3.0
percent (Stephen, 1980). Because the
steady-state BCFs for lipid-soluble
compounds are proportional to percent
lipids, bioconcentration factors for fish
and shellfish can be adjusted to the
average percent lipids for aquatic
organisms consumed by Americans. For
many lipid-soluble pollutants, there
exists at least one BCF for which the
percent lipid value was measured for the
tissues for which the BCF is determined.
With 3.0 percent as the weighted
average percent lipids for freshwater'
and estuarine fish and shellfish in the
average diet, a BCF, and a
corresponding percent lipid value, the
weighted average bioconcentration
factor can be calculated.
Example:
Weighted average percent lipids for
average diet=3.0 percent
Measured BCF of 17 for
trichloroethylene with bluegills at
4.8 percent lipids
Weighted average. BCF for average
diet equals
17 x 3.OX = 10.6
4.8%
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Federal Register / Vol. 45. No. 231 / Friday. November 28, 1980 / Notices
79349
As an estimate, 10.6 Is used for the
BCF.
In those cases where an appropriate
bioconcentration factor Is not available,
the equation "Log BCF= (0.85 Log P)-
0.70" can be used (Veith, et al. 1979) to
estimate the BCF for aquatic organisms
containing about 7.6 percent lipids
(Veith, 1880) from.the octanol/water
partition coefficient P. An adjustment
for percent llplds in the average diet
versus 7,6 percent Is made in order to
derive the weighted average
bioconcentration factor.
For non-lipid-sofuble compounds, the
available BCFs for the edible portion of
consumed freshwater and estuarine fish
and shellfish are weighted according to
consumption factors to determine a
weighted BCF representative of the
average diet
B. Pharmacokinetjcs
This section summarizes the available
information on the absorption,
distribution, metabolism, and
elimination of the compound(s) in
humans and experimental mammals.
Conceptually, such Information is useful
in validation of inter- and intraspecies
extrapolations, and In characterizing the
modes of toxic action. Sufficient .
Information on absorption and excretion
in animals, together with a knowledge of
ambient concentrations in water, food,
and ah-, could be useful in estimating
body burdens of chemicals in the human
population. Distribution data which
suggest target organs or tissues are
desirable for interspecies comparison
techniques. In terms of the derivation of
criteria, pharmacoklnetic data are
essential to estimate equivalent oral *
doses based on data from Inhalation or
other routes of exposure.
C. Effects
This section summarizes information
on biological effects in both humans and
experimental mammals resulting in;
acute, subacute, and chronic toxiclty,
synergism and/or antagonism,
teratogenicity. mutagenidty. or
carcinogenicity;
The major goal of this section Is to
survey the suitability of the data for use
in assessment of hazard and to
determine which biological end-point,
i.e., non-threshold, threshold, or
orgaholeptic, should be selected for use
in criterion formulation.
Because this section attempts to
assess potential human health effects,
data on documented human effects are
thoroughly evaluated. However, several
factors inherent in human
epidemiological studies usually preclude
the use of such data in generating water
quality criteria. These problems, as
summarized by the National Academy
of Sciences (NAS, 1977) are as follows;
1, Epidemiology cannot tell what
effects a material will have until after
humans have been exposed. One must
not conduct .what might be hazardous
experiments on man,
2, If exposure has been ubiquitous, it
may be impossible to assess the effects
of a material, because there Is no
unexpoaed control group. Statistics of
morbidity obtained before use of a new
material can sometimes be useful, but
when latent periods are variable and
times of Introduction and removal of
materials overlap, historical data on
chronic effects are usually
unsatisfactory.
3. it is usually difficult to determine
doses in human exposures.
4, Usually, it is hard to identify small
changes in common effects, which may
nonetheless be important If the
population Is large.
5. Interactions in a "nature-designed"
experiment usually cannot be
controlled.
Although these problems often
prevent the use of epidemiological data
in quantitative risk assessments,
qualitative similarities or differences
between documented effects in humans
and observed effects in experimental
mammals are extremely useful In testing
the validity of animal-to-man
extrapolations. Consequently, in each
case, an attempt is made to identify and
utilize both epldemiologic and animal
dose-response data. Criteria derived
from such a confirmed data base are
considered to be reliable. .
The decision to establish a criterion
based on a non-threshold model is made
after evaluating all available
Information on carcinogenicity and
supportive Information on mutagenicity.
The approach and conditions for the
qualitative decision of carcinogenicity
are outlined in the U.S. EPA Interim
Cancer Guidelines {41FR 21402), in a
report by Albert, et al. (1977), and In the
Lnteragency Regulatory Liaison Group
(IRLG) guidelines on carcinogenic risks
(IRLG. 1979). It is assumed that a
substance which induces a statistically
significant carcinogenic response in
animals has the capacity to cause
cancer in humans. A chemical which
has not induced a significant cancer
response in humans or experimental
animals is not identified as a
carcinogen, even though its metabolites
or close structural analogues might
induce a carcinogenic response or it was
shown to be mutagenic in an in vitro
system.
It is recognized that some potential
human carcinogens may not be
identified by the guidelines given above.
For example, compounds for which
there is plausible but weak qualitative
evidence of carcinogenicity in *
experimental animal systems (such as
data from mouse skin painting or strain
A mouse pulmonary adenoma) would be
Included In this category. The derivation
of a criterion for human consumption
from these studies In not valid.
regardless of the qualitative outcome. In
addition, there are certain compounds -•
(e.g., nickel and beryllium) which were
shown to be carcinogenic in humans
after inhalation exposure by chemical
form, but have induced thus far no
response in animals or humans via
ingesting their soluble salts.
Nevertheless, a non-threshold criterion
is developed for beryllium because
tumors have been produced in animals
at a site removed from the site of
administration; in contrast, a threshold
criterion is recommended for nickel
because there is no evidence of tumors
at sites distant resulting from
administration of nickel solutions by
either Ingestion,or Injection.
For those compounds which were not
reported to induce carcinogenic effects
or for those compounds for which
carcinogenic data are lacking or
Insufficient, an attempt is made to
estimate a no-effect level. In many
respects, the hazard evaluation from
these studies is similar to that of
bloassays for carcinogenldty. In order
to more closely approximate conditions
of human exposure, preference is given
to chronic studies involving oral
exposures in water or diet over a
significant portion of the animal life
span. Greatest confidence is placed In
those studies which demonstrate dose-
related adverse effects as well as no-
effect levels.
There is considerable variability in
the biological endpoints used to define a
no-effect level. They may range from
gross; effects, such as mortality, to more
subtle biochemical, physiological, or
pathological changes. Teratogenicity,
reproductive impairment, and
behavioral effects are significant toxic
consequences of environmental
contamination. In instances where
carcinogenic or other chronic effects
occur at exposure levels, below those
causing teratogenicity, reproductive
impairment, or behavioral effects, the
former are used in deriving the criterion.
For most of the compounds evaluated
thus far, teratogenicity and reproductive
impairment occur at doses near
maximum tolerated levels with dose
administration schedules well above
estimated environmental exposure
levels. Moreover, information on
behavioral effects, which could be of
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Federal Register / Vol. 45. No. 201 / Friday, November 28, 1980 / Notices
significance, is not available for most of
the compounds under study.
Consequently, most NOAELs derived
from chronic studies are based either on
gross toxic effects or on effects directly
related; to functional impairment or
defined pathological lesions.
For, compounds on which adequate
chronic tosJcity studies,are not
available, studies on acute and subacute
toxicity assume greater significance.
Acute toxicity studies usually Involve
single exposures at lethal or near lethal
doses. Subacute studies often involve
exposures exceeding 10 percent of the
life span of the test organism, eug.. 90
days for the rat with an average life
span of 30 months. Such .studies are
useful in establishing the nature of the
compound's toxic effects and other
parameters of compound toxicity, such
as target organ effects, metabolic1
behavior, physiological/biochemical
effects, and patterns of retention and
tissue distribution. The utility of acute
and subacute studies in deriving
environmentally meaningful NOELs is
uncertain, although McNamara [1076]
has developed application factors for
such derivations.
In some cases where adequate data
are not available from studies, utilizing
oral routes of administration, no-effect
levels for oral exposures may be
estimated from dermal or Inhalation
studies. Such estimates involve
approximations of the total dose
administered based on assumptions
about breathing rates and/or magnitude
of absorption.
D. Criterion Rationale
This section reviews existing
standards for the chemical(s),
summarizes data on current levels of
human exposure, attempts to identify
special groups at risk, and defines the
basis for the recommended criterion,
Information on existing standards is
included primarily for comparison with
the proposed water quality criteria.
Some of the present standards, such as
those recommended by the
Occupational Safety and Health
Administration (OSHA) or the American
Conference of Governmental Industrial
Hygienists (ACG1H), are based on
toxicologic data but are intended as
acceptable levels for occupational
rather than environmental exposure.
Other levels, such as those
recommended by the National Academy
of Sciences in Drinking Water and
Health (1E77) or in the U.S. EPA Interim
Primary Drinking Water Standards, are
more closely related to proposed water
quality criteria. Emphasis is placed on
detailing the basis for the existing
standards wherever possible.
Summaries of current levels of human
exposure, presented in this section,
specifically address the suitability of the
data to derive water quality criteria. The
Identification of special groups at risk,
either because of geographical or
occupational differences in exposure or
biological differences in susceptibility to
the compoundfs], focuses on the impact
that these groups should have on the
development of water quality criteria.
The basis for the recommended
criteria section summarizes and
qualifies all of the data used in
developing the criteria. •
IV. Guidelines for Criteria Derivation
The derivation of water quality
criteria from laboratory animal toxicity
data is essentially a two-step procedure.
First, a total daily intake for humans
must be estimated which establishes
either a defined level of risk for non-
threshold effects or a no-effect level for
threshold effects. Secondly, assumptions
must be,made about the contribution of
contaminated water and the
consumption offish/shellfish to the total
daily intake of the chemical. These
estimates are then used to establish the
tolerable daily intake and consequently
the water quality criterion,
A, Non-Threshold Effects
After the decision has been made that
a compound has the potential for
causing cancers in humans and that .
data exist which permit the derivation
of a criterion, the water concentration
which is estimated to cause a lifetime
carcinogenic risk of 10"* is determined.
The lifetime carcinogenidty risk Is the
probability that a person would get
cancer sometime in his or her life
assuming continuous exposure to the
compound. The water concentration is
calculated by using the low-dose
extrapolation procedure proposed by
Crump (t980). This procedure is an
improvement on the multistage low dose
extrapolation procedure by Crump, et al.
(1977).
The data used for quantitative
estimates are of two types: (1) lifetime
animal studies, and (2) human studies
where excess cancer risk has been
associated with exposure to the agent.
In animal studies it is assumed, unless
evidence exists to the contrary, that if a
carcinogenic response occurs at the
dose levels used in the study, then
proportionately lower responses will
also occur at all lower doses, with an -
incidence determined by the
extrapolation model discussed below.
1. Choice of Model.
• There is no really solid scientific basis
for any mathematical extrapolation
model which relates carcinogen
exposure to cancer risks at the
extremclylbtv levels of concentration
that must be dealt with in evaluating the
environmental hazards. For practical
reasons, such low "levels of risk cannot
be measured directly either.using animal
experiments pr.epidemiologic studies.
We must, therefore, depend on our
current understanding of the
mechanisms of carcinogenesis for
guidance as to which risk model to use.
At the present time, the dominant view
of the carcinogenic process involves the
concept that most agents which cause
cancer also cause irreversible damage to
DN A. This position is reflected by the
fact that a very large proportion of
agents which cause cancer are also
mutajenic. There is reason to expect
that the quontal type of biological
response that is characteristic of
mutagenesls is associated with a linear
non-threshold dose-response
relationship. Indeed, there is substantial
evidence frcm mutagenesia studies with
both ionizing radiation and with a wide
variety of chemicals that this type of
dose-response model is the appropriate
one to use. This is particularly true at
the lower end of the dose-response
curve; at higher doses, there can be an
upward curvature, probably reflecting
the effects of multistage processes on
the mutagenic response. The linear non-
threshold dose-response relationship is
also consistent with the relatively few
epldemlological studies of cancer
responses to specific agents that contain
enough information to make the
evaluation possible (e.g., radiation-
induced leukemia, breast and thyroid
cancer, skin cancer induced by arsenic
in drinking water, and liver cancer
induced by aflatoxin in the diet). There
is also some evidence from animal
experiments that is consistent with the
linear non-threshold hypothesis (e.g.,
liver tumors induced in mice by 2-
acetylamlnofluorene in the large scale
ED»i study at the National Center of
Toxicologies! Research, and the
initiation stage of the two-stage
carcinogenesis model in the rat liver and
the mouse skin],
Because it has the best, albeit limited.
scientific basis of any of the current
mathematical extrapolation models, the
linear non-threshold model has been
adopted as the primary .basis for risk
extrapolation to low levels of the dose-
response relationship. The risk
assessments made with this model
should be regarded as conservative,
representing the most plausible upper
limit for the risk; ijg., the,true risk is not
likely to be higher than the estimate, but
it could be smaller.
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79351
The mathematical formulation chosen
to describe the linear, non-threshold
dose-response relationship at low doses
islUie improved multistage model
developed by Crump (1980). This model
employs enough arbitrary constants to
"be able to fit almost any monotonically
increasing dose-response data and it
incorporates a procedure for estimating
the largest possible linear slope (in the
05 percent confidence limit sense) at low
extrapolated doses that is consistent
with the data at all dose levels of the
experiment. For this reason, it may be
called a "linearized" multistage model.
2. Procedure of Low-Dose
Extrapolation Based on Animal
Carcinogenicity Data.
A. Description of the Extrapolation
Model
Let P(d] represent the lifetime risk
(probability) of cancer at dose d. The
multistage model has the form
Pfd}=l-exp[-(q.+q,d+q,ds+. . . +qkdk]]
where:
q,>0,andl=0,l. 2,. .
Equivalently,
A(d)=l-exp [-
where:
. ,k
. . +qkd"J]
A(d) - P(d)*P(o).
1 - P(o)
is the extra risk over background rate at
dosed.
The point estimate of the coefficients
qi, 1=0, 1, 2 ..... k. and consequently
the extra risk function A(d) at any given
dose d, is calculated by maximizing the
likelihood function of the data.
The point estimate and the 95 percent
upper confidence limit of the extra risk
A(d) are calculated by using the
computer program GLOBAL 79
developed by Crump and Watson (1979).
Upper 96 percent confidence limits on
the extra risk and lower 95 percent
confidence limits on the dose producing
a given risk are determined from a 95
percent upper confidence limit, q/. on
parameter qi. Whenever qi-*0, at low
doses extra risk A(d) has approximately
the form A(d)=q,xd. Therefore. qiXd
is a 95 percent upper confidence limit on
the extra risk and R/qi* is a 95 percent
lower confidence limit on the dose
producing an extra risk of R. Let L» be
the maximum value of the log-likelihood
function. The upper limit qt* is
calculated buy increasing q1 to a value
q,* such that when the log-likelihood is
again maximized subject to this fixed
value q/ for the linear coefficient, the
resulting maximum value of the log-
likelihood Li satisfies the equation
2(L,-L,) = 2.70554
where 2.70554 is the cumulative 90
percent point of the chi-square
distribution with one degree of freedom.
which corresponds to a 95 percent upper
limit (one-sided). This approach of
computing the upper confidence limit for
the extra risk A(d) is an improvement on
the Crump, et al. (1977) model. The
upper confidence limit for the extra risk
calculated at low doses is always linear.
This is conceptually consistent with the
linear nonthreshold concept discussed
earlier. The slope qi* is taken as an
upper bound of the potency of the
chemical in Inducing cancer at low
doses.
In fitting the dose-response model the
number of terms in the polynomial g is
chosen equal to (h-1), where h is the
number of dose groups in the
experiment, including the control group.
Whenever the multistage model does
not fit the data sufficiently, data at the
highest dose is deleted and the model is
refitted to the rest of the data. This is
continued until an acceptable fit to the
data is obtained. To determine whether
or not a fit is acceptable, the chi-square
statistic:
(1 - Pi)
is calculated, where N, is the number of
animals in the 1th dose group, X( is the
number of animals in the 1th dose group
with a tumor response; P, is the
probability of a response in the 1th dose
group estimated by fitting the multistage
model to the data, and h is the number
of remaining groups.
The fit is determined to be
unacceptable whenever chi-square (X1)
is larger than the cumulative 99 percent
point of the chi-square distribution with
f degrees of freedom, where f equals the
number of dose groups minus the
number of non-zero multistage
coefficients.
3. Selection and Form of Data used to
Estimate Parameters in the
Extrapolation Model.
For some chemicals, several studies in
different animal species, strains, and
sexes each conducted at several doses
and different routes of exposure are
available. A choice must be made as to
which of the data sets from several
studies are to be used in the model. It is
also necessary to correct for metabolism
differences between species and for
differences in absorption via different
routes of administration. The
procedures, listed below, used in
evaluating these data are consistent
with the estimate of a maximum-likely-
risk.
a. The rumor incidence data are
separated according to organ sites or
tumor types. The set data (i.e.. dose and.
tumor incidence) used in the model is
set where the incidence is statistically
significantly higher than the control for
at least one test dose level and/or
where the tumor incidence rate shows a
statistically significant trend with
respect to dose level. The data set which
gives the highest estimate of lifetime
carcinogenic risk q/ is selected in most
cases. However, efforts are made to
exclude data sets which produce
spuriously high risk estimates because
of a small number of animals. That is, if
two sets of data show a similar dose-
response relationship and one has a
very small sample size,'the set of data
which, has the larger sample size is
selected for calculating the carcinogenic
potency,
b. If there are two or more data sets of
comparable size which are identical
with respect to species, strain, sex, and
tumor sites, the geometric mean of q,*,
estimated from each of these data sets is
used for risk assessment. The geometric
mean of numbers A,, A, Am is
defined as (AiXA,X . . . XAn,)1/m
c. If sufficient data exist for two or
more significant tumor sites in the same
study, the number of animals with at
least one of the specific tumor sites
under consideration is used as Incidence
data in the model.
d. Following the suggestion of Mantel
and Schneidennan (1975), we assume
that rag/surface area/day is an
equivalent dose between species. Since
to a close approximation the surface
area is proportional to the %rds power
of the weight as would be the case for a
perfect sphere, the exposure in mg/%rds
power of the body weight/day is
similarly considered to be an equivalent
exposure. In an animal experiment, this
equivalent dose is computed in the
following manner
Let:
Induration of experiment
U=duratlon of exposure
m=average dose per day In mg during
administration of the agent (I.e.. during 1,)
VV=average weight of the experimental
animal.
Then, the lifetime average exposure is
. le X HI
Le x W2/3
Often exposures are not given in units
of rag/day, and it becomes necessary to
convert the given exposures into mg/
day. For example, in most feeding
studies, exposure is expressed as ppm in
the diet. In this case the exposure (mg/
day] is derived by: m = ppm x F x r
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
where ppm is parts per million of the
carcinogenic agent in the diet. F is the
weight of the food consumed per day in
kgms, and r is the absorption fraction.
In the absence of any data to the
contrary, r is assumed to be one. For a
uniform diet the weight of the food
consumed is proportional to the calories
required, which, in turn, is proportional .
to the surface area or the %rds power of
the weight, so that; mappmxW*'*xr or
m
ppm
,2/3
rW
As a result, ppm in the diet is often
assumed to be an equivalent exposure
between species. However, we feel that
this is not justified since the calories/kg
of food is significantly different in the
diet of man vs. laboratory animals,
primarily due to moisture content
differences. Instead, we use an
empirically derived food factor, f=F/W,
which is the fraction of a species body
weight that Is consumed per day as
food. We use the rates given below.
w
i
Mice.
70 04)28
0-35 0.05
0.03 0,13
Thus, when the exposure is given as a
certain dietary concentration in ppm, the
exposure in ing/ W2' * is
ITL a ppm x F «.
r x W2/3 W2/3
- PP«n x f x wl/3
When exposure is given in terns of
mg/kg/day<=m/Wr=s the conversion is
simply:
•>.. a S X Wl/3
rWZ/3
When exposure is via inhalation, the
calculation of dose can be considered •
for two cases where (1) the carcinogenic
agent is either a completely water-
soluble gas or an aerosol and is
absorbed proportionally to the amount
of air breathed in, and (2) where the
carcinogen is a poorly water-soluble gas
which reaches an equilibrium between
the air breathed and the body
compartments. After equilibrium is
reached, the rate of absorption of these
agents is expected to be proportional to
metabolic rate, which in turn is
proportional to the rate of oxygen
consumption, which in turn is a function
of surface area.
Case 1
Agents that are in the form of
paniculate matter or virtually
completely absorbed gases such as SO»
can reasonably be expected to be
absorbed proportional to the breathing
rate. In this case the exposure in mg/day
may be expressed as: m=Ixvxr where
I is inhalation rate per day in m', v is
mg/m* of the agent in air, and r is the
absorption fraction.
The Inhalation rates, I, for various
species can be calculated from the
observation [FASEB, 1074) that 25 gm
mice breathe 34.B liters/day and 113 gm
rats breathe 105 liters/day. For mice and
rats of other weights, W, (expressed in
kg], the surface area proportionality can
be used to determine breathing rates (in
m'/day) as follows:
For mice, 1=0.0345 (W/0.025)*'»mV
day
For rats, 1-0.105 (W/0.113)"tayday
For humans, the values of 20 m'/day *
is adopted as a standard breathing rate
(ICRP, 1977).
The equivalent exposure in mg/W*'*
for these agents can be derived from the
air intake data in a way analogous to
the food intake data. The empirical
factors for the air intake per kg per day,
i=I/W based upon the previously stated
relationships, are as tabulated below.
w
w
Men
Rat
Mica
70 0.28
, OM 0.04
. 0.03 U
Therefore, for participates or completely
absorbed gases, the equivalent exposure
iamg/Wtr>is;
m ......
w2/3
In the absence of empirical data or a
sound theoretical argument to the
contrary, the fraction absorbed, r, is
assumed to be the same for all species.
Case 2
The dose in mg/day of partially
soluble vapors is proportional to the 0,
consumption which in turn is
proportional to Wa"and to the
solubility of gas in body fluids, which
can be expressed as an absorption
coefficient r for the gas. Therefore, when
expressing the Ot consumption as 0«=k
W" 8, where k is a constant independent
* From "Recommendation of the International
Commission on Radiological Protection," page 9, the
average breathing rate IB 10* cm'per 8-hour work
day and 2 X10' cm' in 24 hours.
of species, it follows that m=k W"»
x r or
kvr
As with Case 1, in the absence of
experimental information or a sound
theoretical argument to the contrary, the
absorption fraction, r, is assumed to be
the same for all species. Therefore, for
these substances a certain concentration
in ppm or ji/ma In experimental animals
is equivalent to the same concentration
in humans. This is supported by the
observation that the minimum alveolar
concentration, necessary to produce a
given "stage" of anesthesia, is similar in
man and animals (Dripps, et al. 1977).
When the animals were exposed via the
oral route and human exposure is via
inhalation or vice-versa, the assumption
is made, unless there is pharmacokinetic
evidence to the contrary, that absorption
is equal by either exposure route.
e. If the duration of experiment (L.) is
leas than the natural life span of the test
animal (L), the slope q«*. or more
generally the exponent g(d), is increased
by multiplying a factor (L/L,)1. We
assume that if the average dose, d, is
continued, the age specific rate of
cancer will continue to increase as a
constant function of the background
rate. The age specific rates for humans
increase at least by the 2nd power of the
age and often by a considerably higher
power, aa demonstrated by Doll (1071).
Thus, we would expect the cumulative
tumor rate to increase by at least the 3rd
power of age. Using this fact, we assume
that the slope qi*. or more generally, the
exponent g(d), would also increase by at
least the 3rd power of age. As a result, if
the slope 0,1* [or g(d)] is calculated at
age L,. we would expect that if the
experiment had been continued for the
full life span, L, at the given average
exposure, the slope qt* [or g[d)] would
have been increased by at least (L/L*)1.
This adjustment is conceptually
consistent to the proportional hazard
model proposed by Cox (1972) and the
time-to-tumor model considered by
Crump, et al. (1977) where the
probability of cancer at age t and dose d
is given by P(d,t)=l-exp[-f(t)Xg(d)]
4. Calculation of Carcinogenic Potency
Based on Human Data. If human
epidemiology studies and sufficiently
valid exposure information are available
for the compound, they are always used
in some way. If they show a
carcinogenic effect, the data are
analyzed to give an estimate of the
linear dependence of cancer rates on
lifetime average dose, which is
equivalent to the factor q,*. If they show
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices 79353
no carcinogenic effect when positive
animal evidence la available, then It is
assumed that a risk does exist but it Is
smaller than could have been observed
in the epidemiologic study, and an upper
limit of the caacer Incidence is
cajculated assuming hypotheticaJly that
the true incidence is just below the level
of detection in the cohort studied, which
is determined largely by the cohort size.
Whenever possible, human data are
used in perference to animal bioassay
data.
In human studies, the response is
measured in terms of the relative risk of
the exposed cohort of individuals
compared to the control group.in the
analysis of this data, it is assumed that
the excess risk, or relative risk minus
one, R(X)-1. is proportional to the
lifetime average exposure, X, and that it
is the same for all ages. It follows that
the carcinogenic potency Is equal to
PUX)-1]/X multiplied by the.lifettme
risk at that site in the general
population. Except for an unusually
well-documented human study, the
confidence limit for the excess risk is
not calculated, due to the difficulty in
accounting for the uncertainty inherent
in the data (exposure and cancer
response).
5. Calculation;of Water Quality
Criteria/After the value of q/ in (mg/-
kg/day}"1 has been determined, the
lifetime risk, P, from an average daily
exposure of x mg/kg/day is found from
the equation P=qi*x Therefore, if the
lifetime risk is set at P=.l
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79354
Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
Indication of carclnogenieJty" la
interpreted as the absence of
carcinogenic! ty data from animal
experimental studies or human
epidemiology. Available short-term
carcinogeniclty screening tests are
reported in the criteria documents, but
they are not used either for derivation of
numerical criteria nor to rule out the
uncertainty factor approach.
Because of the high degree of
judgment involved in the selection of a
safety factor, the criterion derivation
section of each document should
provide a detailed discussion and
justification far both the selection of the
safety factor and the data to which it ia
applied. This discussion should reflect a
critical review of the available data
base. Factors to be considered include
number of animals, species, and
parameters tested; quality of controls;
doae levels; route; and dosing schedules.
An effort should be made to
differentiate between results which
constitute a lexicologically sufficient
data base and data which may be
spurious In nature.
2. Use of Acceptable Daily Intake
(ADI). For carcinogens, the assumption
of low dose linearity precludes the
necessity for defining total exposure in
the estimation of increased incremental
risk. For non-carcinogens, ADIs and
criteria derived therefrom are calculated
from total exposure data that Include
contributions from the diet and air. The
equation used to derive the criterion (C)
is: C=ADI-(DT+IN}/[2 l-f-(Q,OQ8! kg
X R)] where 21 is assumed daily water
consumption, 0.0085 kg is assumed daily
fish consumption, R is bioconcentration
factor in units of I/kg, DT is estimated
non-fish dietary intake, and IN is
estimated daily intake by inhalation.
If estimates of IN and DT cannot be .
provided from experimental data, an
assumption must be made concerning
total exposure. It Is recognized that
either the inability to estimate DT and
IN due to lack of data or the wide
variability in DT and IN in different
states may add an additional element of
uncertainty to the criterion formulation
process. In terms of scientific validity,
the accurate estimate of the Acceptable
Daily Intake is the major factor in
satisfactory derivation of water quality
criteria.
3. Use of Threshold Limit Values or
Animal Inhalation Studies. Threshold
Limit Values (TLVs) are established by
the American Conference of
Governmental and Industrial Hygienists
(ACGIH) and represent 8-hour time-
weighted average concentrations in air
that are intended to protect -workers
from various adverse health effects over
a normal working lifetime. Similar
values are set by NIOSH (criteria) and
OSHA (standards] for 10- and 8-hour
exposures, respectively. To the extent
that these values are baaed on sound
toxicologic assessments and have been
protective in the work environment, they
provide useful information for deriving
or evaluating water quality criteria.
However, each TLV must be carefully
examined to determine if the basis of
the TLV contains data which can be
used directly to derive a water quality
criterion using the uncertainty factor
approach. In addition, the history of
each TLV must be examined to assess
the extent to which it has assured
worker safety. In each case, the types of
effects against which TLVs are designed
to protect are examined In terms of their
relevance to exposure from water. It
must be demonstrated that the chemical
is not a localized irritant and that there
is no significant effect at the site of
entry irrespective of the routes of
exposure (i.e., oral or inhalation).
If the TLV or similar value is
recommended as the basis of the
criterion, consideration of the above
points is explicitly stated in the criterion
derivation section of the document.
Particular emphasis is placed on the
quality of the TLV relative to the
available toxicity data that normally is
given priority over TLVs or similar
established values. If the TLV can be
Justified as the basis for the clrterion,
then the problems associated with the
estimation of acceptable oral doses from
inhalation data must be addressed.
Estimating equivalencies of dose-
response relationships from one route of
exposure to another introduces an
additional element of uncertainty in the
derivation of criteria. Consequently,
whenever possible, ambient water
quality criteria should be based on data
involving oral exposures, if oral data are
insufficient, data from other routes of
exposure may be useful in the criterion
derivation process.
Inhalation data, including TLVs or
similar values, are the most common
alternatives to oral data. Estimates of
equivalent doses can be baaed upon: (1)
available pharmacokinetic data for oral
and inhalation routes, (2) measurements
of absorption efficiency from ingested or
inhaled chemicals, or (3) comparative
excretion data when the associated
metabolic pathways are equivalent to
those following oral ingestion or
Inhalation. Given that sufficient
pharmacokinetic data are available, the
use of accepted pharmacokinetic models
provides the most satisfactory approach
for dose conversions. However, if
available pharmacokinetic data are
marginal or of questionable quality,
pharmacokinetic modeling is
inappropriate.
The Stokinger and Woodward (1958)
approach, or similar models based on
assumptions of breathing rate and
absorption efficiency, represents
possible alternatives when data are not
sufficient to justify pharmacokinetic
modeling. Such alternative approaches,
however, provide less satisfactory
approximations because they are not
based on pharmacokinetic data.
Consequently, in using the Stokinger
and Woodward or related models, die
uncertainties inherent In each of the
assumptions and the basis of each
assumption must be clearly stated in the
derivation of the criterion.
The use of data pertaining to other
routes of exposure to derive water
quality criteria may also be considered.
As with inhalation data, an attempt is
made to use accepted toxicologic and
pharmacokinetic principles to estimate
equivalent oral doses. If simplifying
assumptions are used, their bases and
limitations must be clearly specified.
Because of the uncertainties involved
in extrapolating from one route of
exposure to another and the consequent
limitations that this may place on the
derived criterion, the decision to
disallow such extrapolation and
recommend no criterion is highly
judgmental and must be made on a c.v^
by-case basis. A decision for or against
criteria derivation must balance the
quantity and quality of the available
data against a perceived risk to the
human population.
If the Stokinger and Woodward (1S58)
approach is used to calculate an ADI
from a TLV, the general equation is:
ADI=TLVxBRxpExdxAA/(AoXSF)
where:
s Acceptable daily intake in mg
TLVt= Concentration in air in mg/m'
DE*s Duration of exposure In hours per day
d =5 days/7 days
AA=Efficiency of absorption from air
AO= Efficiency of absorption bom oral
exposure
SF=Safety factor following guidelines given
above
BR= Amount of air breathed per day; assume
10 IB*
For deriving an ADI from animal
toxicity data, the equation is:
ADI=eAxDBxdxAAXBRx70 kg/
(BWAxAoXSF) where:
ADI = Acceptable dally intake in mg
CA = Concentration in sir in mg/m*
Dt= Duration of exposure In hours per day
d= Number of days exposed/number of days
observed
AA=Efficiency of absorption from air
BR = Volume of air breathed per day in m =
70 kg= Assumed human body weight
BWA=Body weight of experiments! animals
in kg
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Federal Register / Vol. 4S. No. 231 / Friday.. November 2B. 19BO / Notices
7B355
0 = Efficiency of absorption from oral
exposure
?m Safety factor following guidelines given
above.
lore formal pharmacokinetic models
tust be developed on a compound-by-
nmpound basis.
It should be noted that the safety
ictors used in the above formulae are
Ucnded to account for species
. ariability. Consequently, the mg/
urface area/day conversion factor is
ot used In the derivation of toxicity
a sed criterion.
*. Organoleptic Criteria
Organoleptic criteria define
oncentratlons of materials which
npart undesirable taste and/or odor to
/ater. In developing and utilizing such
riteria two factors must be appreciated:
le limitations of most organoleptic data
rid the human health significance of
rganoleptlc properties.
The publications which report taste
nd odor thresholds are, with very few .
xceptions, cryptic in their descriptions
'f test methodologies, number of
ubjects tested, concentration: response
elationships, and sensory
.haracterisUca at specific
.oncentrations above threshold. Thus,
he quality of organoleptic data is often
ignificantly less than that of toxicologlc
iata used in establishing other criteria,
Consequently, a critical evaluation of
he available organoleptic data must be
nade and the selection of the most
ippropriate data base for the criterion
nust be based on sound scientific
udgment. .
Organoleptic criteria,are not based on
oxicologic information and have no
lirect relationship to potential adverse
lunian health effects. Although
.ufficlently Intense organoleptic
-.haracteristics could result in depressed
luid Intake which, in turn, might
iggravate a variety of functional disease
itales (i.e., kidney and circulatory
iiseases), such effects are not used In
he derivation process of organoleptic
. -.riteria unless available data would
ndicate an indirect human health effect
/la decreased fluid consumption,
criteria derived solely from organoleptic
iata are based upon aesthetic qualities
inly.
Since organoleptic and human health
iffects criteria are based on different
•ndpoints, a distinction must be made
Between these two sets of information.
in criteria summaries involving both
types of data, the following format is_
jscd:
For comparison purposes, two approaches
^/ere used to derive criterion levels for
. Based on available toxicity data.
•'or the protection ofT>ubIic health the derived
level is —-. Using available organolepttc
data, for controlling undesirable taste and
odor quality of ambient water the estimated
level is . It should be recognized that
organoleptic data as a basis for establishing a
water quality criteria have no demonstrated
relationship to potential adverse human
health affects.
In those instances where a level to
limit toxicity cannot be derived, the
following statement is to be
appropriately Inserted:
Sufficient data are not available tor
• to derive a level which would
protect against the potential toxicity of this .
compound.
D. Criteria for Chemical Classes
A chemical class is broadly defined as
any group of chemical compounds which
are reviewed in a single risk assessment
document. In criterion derivation,
isomers should be regarded as a part of
a chemical class rather than as a single
compound. A class criterion is an
estimate of risk/safety which applies to
more than one member of a class. It
involves .the use of available data on
one or more chemicals of a class to
derive criteria for other compounds of
the same class In the event that there
are insufficient data available to derive
compound-specific criteria.
A class criterion usually applies to
each member of a class rather than to
the sum of the compounds within the
clasfl, While the potential hazards of
multiple toxicant exposure are not to be
minimized, a criterion, by definition,
most often'applies to an individual
compound; Exceptions may be made for
complex mixtures which are produced,
released, and toxicologieslly tested as
mixtures (e.g., toxaphene andPCBs). For
such exceptions, some attempt is made
to assess the effects of environmental
partitioning (I.e., different patterns of
environmental transport and
degradation) on the validity of the
criterion. If these effects cannot be
assessed, an appropriate statement of
uncertainty should accompany the
criterion.. .'.- ; ; .••;•: -..•. ••, '•' /
Since relatively minor structural
changes within a class of compounds
can have pronounced effects on their
biological activities, reliance on class
criteria should be minimized. Whenever
sufficient toxicologic, data are available
on a chemical within a class, a
compound-specific criterion should be
derived. Nonetheless, for some chemical
classes, scientific judgment may suggest
a sufficient degree of similarity among
chemicals within a class to justify a
class criterion applicable to some of all
members of a class.
The development of a class criterion
takes into consideration the following:
3, A detailed review of the chamica] and
physical properties of chemicals within the
group should be made. A dose relationship
within the class with respect to chemical
acitivity would suggest a similar potential to
reach common biological sites within tissues.
Likewise, similar lipld solubilities would
suggest the possibility of comparable
absorption and tissue distribution.
2. Qualitative and quantitative data for
chemicals within the group are examined.
Adequate toxicologic data on a number of
compounds within a group provides a more
reasonable basis for extrapolation to other
chemicals of the same class than minimal
data on one chemical or a few chemicals
within the group.
3. Similarities In the nature of the
toxicologic response to chemicals In the class
provides additional support for the prediction
that the response to other members of the
class may be similar. In contrast, where the
biological response has been shown to differ
markedly on a qualitative and quantitative
basis for chemicals within a class, the
extrapolation of a criterion to other members
of that class is not appropriate.
4, Additional support for the validity of
extrapolation of a criterion to other members
of a class could be provided by evidence of
similar metabolic and pharmacokinetic data
for some members of the class. .
Based on the above considerations, it
may be reasonable In some cases to
divide a chemical class into various
subclasses. Such divisions could be
based on biological endpoints (e.g..
carcinogens /non-carcinogens), potency,
and/or sufficiency of data (e.g., a
criterion for some members of a class
but no criterion for others]. While no a
priori limits can be placed on the extent
of subclassification, each
subclaasification must be explicitly
justified by the available data.
Class criteria, if properly derived and
supported, can constitute valid scientific
assessments of potential risk/safety.
Conversely, the development of a class
criterion from an insufficient data base
can lead to serious errors in
underestimating or overestimating risk/
safety and should be rigorously avoided.
Although scientific judgment has a
proper role in the development of class
criteria, such criteria are useful and
defensible only if they are based on
adequate data and scientific reasoning.
The definition of sufficient data on
similarities in physical, chemical,
pharmacokinetic, or toxicologic
properties to justify a class criterion
may vary markedly depending on the
degree of structural similarity and the
gravity of the perceived risk.
Consequently, it is imperative that the
criterion derivation section of each
document in which a class criterion is
recommended explicity address each of
the key issues discussed above, and
define, as clearly as possible, the
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79356
Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
. limitations of the proposed criterion as
well as the type of data needed to
generate a compound-specific criterion.
A class criterion should be abandoned
when there is sufficient data availabe to
derive a compound-specific criterion
which protects against the biological
effect of primary concern; e.g., the
availability of a good subchronic study
would not necessarily result in the
abandonment of a class criterion based
on potential carcinogenicity.
The inability to derive a valid class
criterion does not, and should not,
preclude regulation of a compound or
group of compounds based on.concern
for potential: human health effects. The
failure to recommend a criterion is
simply a statement that the degree of
concern cannot be quantified based on
the available data and risk assessment
methodology.
E. Essential Elements
Some chemicals, particularly certain
metals, are essential to biological
organisms at low levels but may be
toxic and/ or carcinogenic at high levels.
Because of potential toxic effects, it is
legitimate to establish criteria for such
essential elements. However, criteria
must consjder essentiality'and cannot
be established at levels which would
result In deficiency of the element in the
human population.
Elements are accepted as essential if
listed by NAS Food and Nutrition Board
or a comparably qualified panel.
Elements not yet determined to be
essential but for which supportive data
on essentiality exists need to be further
reviewed by such a panel
To modify the toxicity and
carcinogenicity based criteria,
essentiality must be quantified either as
a "recommended daily allowance"
(RDAj or "minimum daily requirement"
(MDR). These levels,are then compared
to estimated daily doses associated with
the adverse effect of primary concern.
The difference between the RDA or
MDR and the daily doses causing a
specified risk level for carcinogens or
ADIs for non-carcinogens defines the
spread of daily doses from which the
triterion may be derived. Because errors
are inherent in defining both essential
and maximum tolerable levels, the
criterion is derived from dose levels .
near the center of such a dose range.
The decision to use either the MDR or
RDA is guided by the spread of the
doses and the quality of the essentiality
and toxicity estimates.
The modification of criteria by
consideration of essentiality must take
into account all routes of exposure. If
water is a significant source of the MDR
or RDA, the criterion must allow for
attainment of essential intake.
Conversely, even when essentiality may
be attained from nonwater sources.
standard criteria derivation methods
may be adjusted if the derived criterion
represents a small fraction of the ADI or
MDR. On a case-by-case basis,'the
modification in the use of the guidelines
may include the use of different safety
factors for non-carcinogens or other
modifications which can be explicitly
justified.
F. Use of Existing Standards
For some chemicals for which criteria
are to be established; drinking water
standards already exist. These
standards represent not only a critical
assessment of literature, but also a body
of human experience since their
promulgation. Therefore, it is valid to
accept the existing standard unless
there is compelling evidence to the
contrary. This decision should be made
after considering the existing standards
vs. new scientific evidence which has
accumulated since the standards have
been established. There are several
instances where the peer review process
recommended usage of the present
drinking water standards.
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Agency for the assessment of carcinogenic
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Cox, C.R. 1972. Regression model and life
tables. Jour. Roy. Slat Soc. B. 34:187.
Crump, K.S; 1979. Dose-response problems
in carcinogenesis. Biometrics. 35:157.
Crump. K.S. 1980. An improved procedure
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Crump. K.S. and WAV. Watson. 1979.
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Doll, R. 1971. Weibull distribution of
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Peto, R. 1973. Weibull distribution for
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38:1040. •
Health Effects Methodology—Authors,
Contributors and Reviewers
Jerry F. Stara, ECAO-Cln, U.S. Environmental
Protection Agency
Elizabeth L. Anderson. OHEA. U.S.
Environmental Protection Agency
Roy E. Albert N.Y. University Medical
School. New York. NY
Patrick R. Durkln, Syracuse Research
Corporation, Syracuse, NY
Steven D. Lutkenhoff, ECAO, ITS.
Environmental Protection Agency
Robert E. McGaughy, CAG, U.S.
Environmental Protection Agency
Charles Ris, OHEA, U.S. Environmental
Protection Agency
Lawrence Anderson, CAG, U.S.
Environmental Protection Agency
Dolph Arnicar, CAG, U.S. Environmental
Protection Agency
Steven Bayard. CAG. U.S. Environmental
Protection Agency
Edward Caiabrese, University of
Massachusetts, Amherst. MA
Thomas Clarkson, University of Rochester,
Rochester. NY •
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Federal Register / Vol. 4S. No. 231 / Friday. November 28. 1980 / Notices 79357
Joseph Cotruvo. ODW, U.S. Environmental
Protection Agency
Christopher DeRosa, ECAO-Cin, U.S
Environmenlal Protection Agency
Kurt Ensleln. Cenesee Computer Center. Inc..
Syracuse, NY
Jeffrey Gaba. OCC U.S. Environmental
Protection 'Agency
Frank Gostomski. OWRS. U.S. Environmental
Protection Agency
Daniel Greathouse, HERL-Cin, U.S.
Environmental Protection Agency
Joseph Areas, Tulane University, New
Orleans, LA
Dev Barnes, OWRS. U.S. Environmental
Protection Agency
David L Bayliss, CAG, UJ. Environmental
Protection Agency
Chao W. Chen, CAG, U.S.-Environmental
Protection Agency
Herbert Cornish, University of Michigan, Ann
Arbor, MI
Kenneth Crump. Science Research Systems,
Int. Huston. LA
Michael Doureon. ECAO-Cln. U.S.
Environmental Protection Agency
John R. Pbwle HI. CAG, U.S. Environmental
Protection Agency
R. John Gamer, HERL-Cin, U.S.
Environmental Protection Agency
Terrence Crady, ECAO-Cin, U.S.
Environmental Protection Agency
Bernard Habeiman, CAG, U.S. Environmental
Protection Agency
Paul Hammond, University of Cincinnati.
Cincinnati, OH
Charallngayya Hiremath, CAG, U.S.
Environmental Protection Agency
Dinko KeJlo, Institute for Medical Research
and Occupational Health, Zagreb, Yugo.
Chang S, Lao, CAG, U.S. Environmental
Protection Agency
Marvin Legator, University of Texas Medical
Branch, Galveston. TX
Jack McGinnlty, OTS. U.S. Environmental
Protection Agency
Debdas Mukerjee. ECAO-Cin, U.S.
Environmental Protection Agency
Ellen OTloherty, University of Cincinnati,
Cincinnati, OH
Fred Passman, Energy Resources Co., Inc.
Cambridge, MA
John F. Risher, ECAO-Cin. U.S.
Environmental Protection Agency
Jeffery Rosenblatt, OTS, U.S, Environmental
Protection Agency
Samuel Shibko, US FDA. Washington, DC
Harry T. Skalaky, Reynolds Metal Company
Todd W. Thorshuid, CAG. U.S.
Environmental Protection Agency
Benjamin VanDuuren, N.Y. University
Medical School, New York, NY
fames R. Withey, National Health and
Welfare Canada Ottawa, Canada
Rolf Hartung, University of Michigan. Ann
Arbor, Ml
Rudolf Jaeger, Harvard School of Public
Health, Cambridge, MA
Arnold M. Kuzmack, CAG. U.S.
Environmental Protection Agency
Si Duk Lee. ECAO-Cin. U.S. Environmental
Protection Agency
Leland McCabe, HERL-Cin, U.S.
Environmental Protection Agency
Myron Mehlman, Mobil OU Corporation, New
York. NY
Jean Munson. University of Cincinnati.
Cincinnati, OH
Nancy Othmer. OGC, U.S. Environmental
Protection Agency
David I. Reisman, ECAO-Cin. U.S.
Environmental Protection Agency
Paula K. Robereon, U.S. Environmental
Protection Agency
H. Daniel Roth, Roth Associates
Dharm V. Singh, CAG, U.S. Environmental
Protection Agency
Robert G. Tardiff. National Academy of
Sciences, Washington, DC
Anne W.' TrontelL Energy Resources Co., Inc.,
Cambridge, MA
John Van Ryzin, Columbia University, New
York. NY
Ronald E Wyzga, Electric Power Research
Institute
Appendix D—Response to Comments on
Guidelines For Deriving Water Quality
Criteria for the Protection of Aquatic
Life and Its Uses
Introduction
Two versions of the Guidelines were .
published in the Federal Register for
comment. The first version (43 FR 21506,
May 18,1978 and 43 FR 29028. July 6,
1979) was simply published for
comment. The second (44 FR 15926.
March 15,1979] was published as part of
the request for comments on the water
quality criteria for 27 of the 65
pollutants. The second version was
meant to be clearer and more detailed
than the first, but very similar
technically. Since the two versions were
so similar, comments on both will be
dealt with simultaneously.
Many comments were received that
no draft water quality criteria for any of
the 65 pollutants should have been
issued for public comment until the
comments on the first version of the
Guidelines had been dealt with
adequately and the Guidelines changed
appropriately. The comments on the first
version were read and the Guidelines
were revised in an attempt to make the
second version clearer and more
detailed than the first However, an
extensive revision of the technical
content of the Guidelines was not
attempted between the first and second
versions-because the Agency was
preparing water quality criteria based
on the Guidelines. The Agency could
have avoided this criticism simply by
not publishing any version of the
Guidelines for comment until March 15,
1978, but this would have greatly
reduced the length of time available for
people to consider the Guidelines and
comment on them. As it was, some
people commented that the comment
period announced on March 15,1979,
was too short.
1. Comment—The procedures used to
derive criteria in the "Red Book" were
upheld in court and probably should still
be used.
Response—The procedures used in
the Guidelines are similar to some of .the f
procedures used to develop criteria in
the "Green Book", "Blue Book", and
"Red Book". The Guidelines are
designed to be more objective and
systematic, to deal more adequately
with residues, and to incorporate the
concept of a minimum data base.
2. Comment—Criteria should be
compilations of critically reviewed data
with no synthesis or interpretation.
Response—Neither P.L 92-500 nor the
Consent Decree specify the form which
a criterion must take. The Consent
Decree (para. 11, p, 14) specifies that
such criteria "shall state, inter alia,
recommended maximum permissible
concentrations". Adequate precedents
have been set In the "Green Book",
"Blue Book", and "Red Book" for the
form of criteria used In the Guidelines.
3. Comment—The Guidelines and
criteria should be developed by a
consensus of aquatic lexicologists rather
than by EPA personnel only.
Response—EPA certainly wants the
Guidelines and the criteria to be as good
as possible and as acceptable to as
many interested people as possible. To
this end, EPA has widely distributed
draft versions of the Guidelines and the
criteria documents, discussed them with
many people, considered the comments
received, and made many significant
technical changes and editorial
revisions. It is questionable whether or
not a true consensus could have been
reached by any means within the time
available. In addition, EPA has a
legislative responsibility which it should
not delegate to someone else.
4, Comment—The Guidelines should
be updated regularly.
Response—The Guidelines are not
being promulgated as a regulation or
directive. The purpose of presenting
these Guidelines is to show how the
water quality criteria for aquatic life
were derived for the 65 pollutants. If
EPA uses these Guidelines again, they
will be revised to take into account new
data, concepts, and ideas.
5. Comment—The objectives, purpose,
and limitations of the Guidelines should
be stated.
Response—The introductory portion
of the Guidelines has been expanded to
address these subjects more fully.
8. Comment—The Guidelines are too
ambiguous.
Response—The Guidelines have been
revised and rewritten, partly to improve
clarity and provide additional details. It
is not possible to provide explicit details
. on all items; in some areas only general
guidance can be provided at this time.
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EPA attempted to clearly and concisely
deal with all Issues which might
significantly affect the resulting criteria
without going into extreme detail on
every potential problem. Because
numerous judgments must be made, a
reasonable amount of experience in
aquatic toxicology will be necessary for
a person to utilize the Guidelines
effectively.
7. Comment—The Guidelines are too
complex.
Response—Deriving a water quality
criterion is a complex exercise because
several different kinds of data and a
wide variety of. organisms need to be
considered. In addition, because data
have been generated using various
procedures, numerous individual
decisions need to be made and the
Guidelines attempt to provide guidance
concerning decisions that seem to need
to be made frequently. The Guidelines
are more complex than initially
envisioned to help insure that criteria
for different pollutants are derived in a
reasonably comparable manner.
Although the process of deriving a water
quality criterion for aquatic life is
complex, the Guidelines help organize
the process into logical components and
steps.
8. Comment—The Guidelines should
be more flexible.
Response—The Guidelines*are meant
to provide guidance and at the same
time allow reasonable flexibility. They
have been used with quite a variety of
pollutants for which the requirements of
the minimum data base are satisfied,
and they seem to be reasonably
appropriate in all cases because the
experiences with these substances were
a major part of the basis for the
Guidelines. If sound scientific evidence
indicates that a particular aspect of the
Guidelines is not appropriate for a
specific substance, then some other
more appropriate procedure should be
used. However, the Guidelines should •
not be changed based on individual
whim or personal preference.
i. Comment—The Guidelines should
take into account synergism and
antagonism by a wide variety of factors
and the effect of the pollutant on
important ecological relationships.
Response—Very little practically
useful information is available on these
factors in connection with the effects of
pollutants on aquatic organisms.
Synergism and antagonism are possible
between numerous combination of two
or more pollutants, and some data
indicate that such interactions are not
only species specific, but also vary with
the ratios and absolute concentrations
of the pollutants and the life stage of the
species. Pollutants may affect the
structure and function of aquatic
ecosystems separate from their effects
on individual species, but practical
applications of such ideas seem very
tenuous at this time. Little information is
available concerning such effects, and
the significance of the available data is
questionable. An obviously important
ecological relationship is the
dependence of higher organisms on
lower organisns for food. Even here, the
existence of numerous lower species
and their adaptability reduces the
Importance of any individual food
species.
10. Comment—The Guidelines should
take into account all identifiable
effects—beneficial as well as harmful.
Response—Few tests have been
conducted to identify beneficial effects
of individual pollutants on aquatic
organisms. However, beneficial effects
are sometimes observed In chronic
toxicity tests at concentrations below
those that cause adverse effects. Usually
in such cases the organisms In low
concentrations of the pollutant are
longer or heavier or reproduce more that
do the controls. Even if such effects are
statistically significant, they are not
Judged as adverse or harmful. On the
other hand, a beneficial effect on one
species may ultimately be to the
detriment of a community if a balance
between species is disturbed. Also, a
concentration that benefits one species
may harm a more sensitive species,
11. Comment—The Guidelines should
take into account analytical
methodology.
Response—The Guidelines do take
into account analytical methodology in
the definition of the substance, when
necessary, but not In deriving the
.numerical value of the criterion.
Concentrations which cannot be
routinely measured accurately can often
be measured accurately by nonroutine
methods and, more importantly, do
sometimes adversely affect aquatic
organisms, When aquatic organisms are
more sensitive than routine analytical
methods, the proper solution Is to
develop better analytical methods, not
to underprotect aquatic life. One use of
criteria should be to identify needs in
analytical chemistry.
12. Comment—The Guidelines should
take into account (a) production and
usage patterns, (b) chemical, physical
and biological factors pertaining to
degradation and fate of pollutants,
Including properties such as solubility in
water, decay rate, persistence, and
transformation pathways, and (c)
whether or not a criterion is needed for
the substance.
Response—Items included in (a} end
(b] may be important in deciding
whether a criterion is needed for a
substance, but the Guidelines are
intended to be used after the decision
has been made that a criterion is *
needed. EPA is presently developing
principles that can be used to decide
whether or not a criterion is needed for
a substance and items such as those
listed above are probably some of the
factors that should be considered when
deciding whether or not a criterion is
needed. If the toxicity of the chemical is
used to evaluate the need for a criterion,
the Guidelines may be useful in the
collection and interpretation of the
available toxicity data.
13. Comment—The Guidelines should
take into account costs to states and
industries, technological feasibility, and
such characteristics of bodies of water
as assimilative capacity, dispersal,
dissipative factors, dilution, hydrology,
mixing zones, and sediment.
Response—Factors such as these
should be considered in developing
standards, but not in deriving criteria.
EPA is presently developing an
implementation policy which will
describe which of the above factors and
which characteristics of the pollutant
should be used, and how they should be
used, in developing standards.
14. Comment—The Guidelines are not
appropriate for establishing a
concentration which may be present in
an effluent.
Response—The Guidelines are for
deriving water quality criteria, not
effluent standards nor mixing zone
standards nor water quality standards.
Water quality criteria will probably be
one factor taken into account in the
development of water quality standards
and toxicity-based effluent standards,
but not technology-based effluent
standards. EPA is presently developing
policies concerning proper use of water
quality criteria in various regulatory
activities.
15. Comment—The derivation of
criteria should be fundamentally a
scientific exercise and should not
employ subjective judgments.
Response—No exercise which
involves the use and interpretation of
data can avoid subjective Judgment.
Indeed, even the generation of scientific
data requires subjective Judgment, such
as how many test organisms to use,
what temperature to use, etc. One may
decide to accept the recommendations
of experts, but this is usually still a
subjective decision. In statistics the
subjective decisions are made on the
basis of probability statements but the
final decisions are still subjective
judgments. Although the development of
the Guidelines and the derivation of
criteria cannot avoid subjective
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79359
decisions, gross extrapolations, wild
assumptions, and novel judgments can
be avoided. One can also avoid using
large safety factors to "make up" for
insufficient data. When some agreement
exists between experts, such as on test
temperature and duration of tests, the
collective opinion can usually be used.
EPA feels that the Guidelines do not go
loo far beyond the state-of-the-art and
do not produce criteria by extrapolating
far beyond the usefulness of the data.
16. Comment—The Guidelines should
not use unproven extrapolations.
Response—EPA feels that the
extrapolations used in the Guidelines
are reasonable for most pollutants.
Probably the most questionable
extrapolation is the acute-chronic ratio.
but even here an arbitrary ratio is not
used. Indeed, the ratio used is usually a
mean of experimentally determined .
acute-chronic ratios for at least three.
not |ust one, species. In addition, the
species must include at least one fish
and one invertebrate. Even this amount
of data does not "prove" the validity of
the extrapolation, but it should provide
reasonable evidence for or against the
use of the ratio with any particular
substance. To achieve reasonable
criteria without using any extrapolations
would require acute and chronic tests
with many more species. This would be
a high price to pay for disallowing any
use of scientific inference in deriving
criteria.
The early versions of the Guidelines
used adjustment factors and sensitivity
factors which were averages derived
•from data for a wide variety of
substances and thus were attempts to
make some extrapolations across all
substances. The present version of the
Guidelines is based on a minimum data
base for each individual pollutant and
the calculations are essentially
pollutant-specific. Thus no
extrapolations are made from one
pollutant to another.
17. Comment—Laboratory tests
3verestimate the toxicity of materials
Decause the test organisms are stressed
ay the artifical conditions.
Response—Laboratory conditions
:ertainly are artificial, but they do not
lecessarily stress the test organisms.
Drganisms which survive, grow, and
eproduce well in the laboratory cannot
>e stressed too much. Organisms in a
aboratory might be considered
ampered because they do not have to
ompete for food and are not subject to
tress due to predators and changing
nd extreme conditions of turbidity,
->mperature, flow, and water quality.
.Iso. laboratory organisms are rarely
jbject to stress from pollutants. Some
oecies probably have longer average
life spans in-laboratories than they do in
field situations.
18. Comment—Laboratory tests
underestimate the toxicity of materials
because the tests are usually conducted
with species which are hardy,
adaptable, and insensitive.
Response—Species which are readily
adaptable to laboratory conditions are
not necessarily insensitive as evidenced
by the great range of sensitivities
obtained in laboratory tests for some
individual pollutants with different
species. In fact, once the the proper .
techniques are developed, a wide
variety of species can survive, grow, and
reproduce well in laboratories. When
the proper techniques are discovered
and a species changes form "difficult" to
"easy", its sensitivity does not change.
Also, some species and life stages which
are fragile and must be handled with
great care are not particularly sensitive.
On the other hand, because so few
species have actually been tested in
laboratories, species which are more
sensitive than any of those tested in
laboratories, species which are more
sensitive than any of those tested
probably exist for most substances.
19. Comment—Laboratory tests are
artificial and contrived and do not
represent the real world.
Response—Laboratory tests are
indeed artificial but they are not
contrived to give results that are
unnecessarily high or low. Organisms in
a laboratory are generally acclimated lo
water and conditions of constant and
desirable quality, whereas in the field
(hey are often subjected to fluctuations
and extremes. Organisms in a
laboratory do not have to compete for
food and are not subject to predators or
pollution. Organisms In the field are
often exposed to more than one
pollutant at a time, with the
combinations and concentrations
changing often.
It is true that aquatic organisms are
usually exposed to instantaneous high
concentrations in laboratory tests, but in
field situations organisms are often not
given much chance to acclimate to spills
or short-term discharges. Also, some
ameliorating effects occur in field, but
not laboratory, situations, but such
effects are not always dependable over
long periods of time. The concentrations
of mitigating anions, suspended solids,
and complexing agents are relatively
constant in some bodies of water, but
not in others. Suspended solids probably
do sorb and detoxify significant
amounts of some pollutants, but high
concentrations of suspended solids also
stress some aquatic organisms. In
addition, organisms are usually fed in
chronic tests, so the test solution
contains suspended solids and dissolved
organic carbon from the food and fecal
matter. Degradation and other
transformations are more likely in field-
situations than in laboratory situations.
but degradation products are not always
less toxic than the undegraded material.
On the other hand, many of these kinds
of considerations will probably be taken
into account when site-specific criteria
and standards are developed under the
implementation policy which is being
developed by EPA.
20. Comment—Laboratory tests are
poor predictors of what will happen in
field situations.
Response—If conditions are
comparable, laboratory toxicity tests are
useful predictors of what will happen in
field situations. The usefulness of such
predictions will depend on how
carefully one accounts for differences
between species, water quality, and the
form of the pollutant. Extrapolations are
much more difficult for some pollutants
than for others. Water quality affects the
toxicity of some pollutants much more
than others, and species differences,
even within families, are much greater
for some pollutants than for others. If
such factors are taken into account,
useful-predictions are possible. In what
is probably the most extensive
comparison available of laboratory and
field data (Geckler, J. R., et aL 1978.
Validity of Laboratory Tests for
Predicting Copper Toxicity in Streams.
EPA-600/3-7&-118. U.S. EPA. Duluth,
MN 208 pp.), It was found that effects
observed in laboratory exposures were
also observed in field exposures.
However, avoidance, which was not
studied in laboratory exposures, was
observed in the field exposures.
Laboratory to field comparisons are not
simple because several factors must be
taken into account, the laboratory test
must be conducted well and the field
observations and measurements must be
extensive. Although adverse effects
observed in laboratory tests will usually
occur in similar field situations, a
problem exists with the bioaccumulation
of some persistent substances. For
example, PCB's seem to bioaccumulate
to much higher levels in some bodies of
water than they do in laboratory tests.
21. Comment—The Guidelines should
place more emphasis on field
information than on laboratory
information.
Response—Field information on
effects of pollutants on natural
populations is acceptable, but the -
collection of definitive information of
this type is high risk and costly. Few
studies on the effects of pollution on
natural populations provide definitive
information because of the multitude of
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Federal Register / Vol.,45. No. 231 / Friday, November 28. 1980 / Notices
variables that need to be taken Into
account. The major advantage of Held
studies la that conditions are natural
(I.e., conditions are not controlled), but
this la also the major problem with field
studies. With uncontrolled conditions,
numerous variables must be taken Into
account, because any individual
variable or combination of variables
may affect the results or Indeed may be
the cause of. the results. Therefore, field
studies on natural populations usually
must last over several seasons and
possibly over more than one year to be
reasonably sura that proposed cause-
and-effect relationships are real.
Another problem with field studies
that are based on statistically significant
differences is the power of the test
Because natural biological, spaciaL and
temporal variability is often rather great,
a large number of samples is usually
required to detect even a moderate
change. A field study, which purports to
show that no change occurred is of no
value if the power of the test calculated
from the experimental design and
observed variability was not high
enough.
. Because field studies are Ugh cost-
high risk ventures, well-designed
laboratory testa are usually much more
cost-effective for obtaining data on (1)
the toxlcity of substances to a variety of
species and (2) the effect of various
water quality characteristics on toxlcity.
Laboratory testa have been shown to
generally be useful predictors of what
happens in a field situation, and so it
makes little sense to conduct high risk,
high coat field studies rather than
laboratory tests. Even definitive field
studies rarely provide enough
information to allow extrapolation of
results to other situations, so field
studies are more useful in reviewing
criteria than in deriving criteria.
22. Comment—Field verification of
laboratory tests and of the Guidelines
are needed. •
Response—Field verification of
laboratory tests and of the Guidelines
are certainly desirable and provide
Information that cannot be obtained In a
laboratory. Field verification studies do
not need to be as risky or as costly as
studies on the effects of a pollutant on
natural populations because verification
studies can be designed (I) as a slde-by-
side comparison of the results of
laboratory tests and field tests or (2)
based on existing results of laboratory
tests.
23. Comment—EPA should allow
criteria to be derived using on-site acute
toxicity tests and an application factor.
Response—This approach is usually
suggested for developing effluent
standards but may be just as applicable
to deriving water quality criteria under
certain conditions. This approach
cannot be used with pollutants whose
most sensitive adverse effect is due to
residues. Also, it can only be used when
the application factor has already been
acceptably determined. Finally, acute
tests must be determined with either an
appropriate range of species or with an
appropriate sensitive species. The
implementation policy presently being
developed by EPA will probably allow
the use of appropriate on-site toxicity
tests In the envelopment of site-specific
criteria and standards.
24. Comment—It Is not dear what
level of protection is intended.
Response—EPA feels that it is not
possible to specify a minimum level of
protection that is necessary to "protect
aquatic life" or even to protect a
particular species for such reasons as:
a. There are so many untested
species.
b. Little practically useful information
is available concerning synergism,
antagonism, ecological relationships,
and avoidance.
c. The effect of factors such as
temperature on toxlcity seems to be
species-specific for at least some
substances.
d. Information is not available
concerning what amount of any effect
would be ecologically significant and
whether the amount is species-specific.
One possible conclusion is that to
protect aquatic life, ail species must be
adequately protected. A possible
extension of this would be that all
criteria should be zero because any
amount of any pollutant may affect
some aquatic organism. Indeed, the
assimilative capacity of body of water
largely depends on the ability of aquatic
life to "process" pollutants and to some
extent, any organism which "processes"
a pollutant is in some way affected by it
The apparent level of protection is
different for each kind of effect (acute
toxlcity to animals, chronic toxicity to
animals, toxicity to plants, and
bioaccumulation) because of the quality
and quantity of the available
information. An attempt was made to
take into account such things as the
importance of the effect, the quality of
the available data, and the probable
ecological relevance of the test methods.
Thus it was felt that with regards to
toxicity to animals it was probably not
necessary to protect all of the species all
of the time, but it certainly seems
appropriate to protect most of the
species most of the time and to protect
important species.
On the other hand, the data base on
toxicity to aquatic plants is usually very
small and a variety of tests and
endpoints have been used, especially
with algae. Also, little information is
available concerning the ecological
relevance of the results of any toxicity
test with algae in a concentrated test
medium, especially because so many
species of algae exist in each body of
water.
The results of bioconcentration tests
with organic chemicals, but not with
inorganic chemicals, can apparently be
extrapolated reasonably well based on
percent lipids from one aquatic animal
species to another, at least within
commercially and recreationally
important species. In addition, die limits
on acceptable concentrations In tissue
are reasonably well defined in some
cases,
These kinds of considerations merely
illustrate the complexity of the problem
and the necessity for making decisions
about each kind of effect individually. In
addition, it is important to distinguish
between the apparent level of protection
provided by the Guidelines and the
actual level of protection which will
result in a field situation from the use of
the implementation policy.
No attempt was made to develop
Guidelines which would achieve a
predetermined numerical level of
protection. For each effect much
desirable information is not available,
and so it would be misleading to imply a
level of sophistication that is not
currently possible. EPA believes that the
present state-of-the-art In aquatic
toxicology does allow some useful
conclusions about the ability of a
substance to adversely affect aquatic
organisms and their uses whenever the
requirements of the minimum data base
are satisfied, with the full realization
that the resulting criterion may be
somewhat overprotective or
underprotective.
In almost all cases more data would
be desirable and so an attempt to reach
the "golden mean" will sometimes result
incriteria being to high and sometimes
too low. One alternative is to derive no
criteria until all desirable data are
available; this is unacceptable because
it will almost always result in no criteria
and no protection. The other alternative
is to apply safety or uncertainty factors
that are inversely proportional to the
adequacy of the data base. In the long
run this approach would encourage the
generation of useful data where it was
most needed, but in the short run would
require many significant subjective
decisions beyond the Current state-of-
the-art
25. Comment—The Guidelines should
not base criteria on '-worst case"
assumptions.
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Response—The phrase "worst case
assumptions" usually refers to the
assumption that both the worst water
quality and the most sensitive life stage
occur at all times. These two
assumptions are a natural result of the
two concepts that criteria should be
constant throughout the year and that
aquatic life is not adequatley protected
if it is not adequately protected
throughout the year. The implementation
policy being developed by EPA will
determine whether site-specific criteria
must be constant throughout the year. If
not then the "worst case assumptions"
will not apply. Although the Guidelines
might be viewed as making the "worst
case assumptions", the implementation
policy will determine whether the site-
specific water quality criteria and
standards will be based on these
assumptions,
26. Comment—Safety factors should
be used to protect against such things as
potential subtle, but important, long
term effects.
Response—Pollutants may cause
many direct and indirect adverse effects
which have not been studied
adequately. For instance, some
substances may make aquatic organisms
more susceptible to disease or other
stresses. In spite of such possibilities,
the available information indicates that
the major possible adverse effects are
covered in the Guidelines and that
adequate protection will usually be
achieved without the use of safety
factors. Safety factors would certainly
offer additional protection, but the
available information: does not show *
that significant additional protection is
needed.
Safety factors of from 10 to 1000 are
often used to protect people mainly
because people feel that people are
more important than aquatic organisms
and because humans are usually
protected on the basis of tests with
other species of animals/ thus resulting
in a greater uncertainty in the
applicability of the results. Complete
protection can only be achieved by
setting all criteria at zero. Unfortunately.
even "Mother Nature" sometimes
seriously harms large groups of aquatic
organisms, such as during droughts or
.severe winter freezes. EPA feels that .
complete protection is neither feasible,
desirable, nor possible. In addition,
aquatic ecosystems can recover from
some'adverse effects.
27. Comment—The Guidelines do not
provide for an adequate margin of
safety.
Response—If "margin of safety" is
interpreted to mean "safety factor", then
ihe Guidelines do not provide a margin
of safety. If the Guidelines are viewed
as deriving criteria for a constant
quality water, then they provide a
margin of safety during those portions of
the year during which the most sensitive
life stage does not occur. Although some
species may occasionally be adversely
affected. EPA feels that the Guidelines
provide adequate safety because
aquatic communities and their uses
should not incur any substantial or
permanent damage. Whether or not site-
specific criteria will have a margin of
safety will depend on how they are
derived;
28. Comment—Criteria should be set
at the least restrictive concentration and
states can then apply more restrictive
concentrations when necessary.
Response—It is unclear what is meant
by the "least restrictive concentration"
but presumably it would be a
concentration which would not protect
very many aquatic communities and •
their uses. This is contradictory to the
concept that criteria are to protect
aquatic life and its uses; The
implementation policy being developed
by EPA will allow site-specific criteria
to be higher or lower than the criteria
derived using the Guidelines, when
adequate Information is available.
29, Comment—The Guidelines should
produce criteria in the form of a
concentration-risk curve with
appropriate confidence limits for each
kind of effect.
Response—EPA feels that a risk
analysis approach is certainly desirable,
but far beyond the state-of-the-art at
this time. When dealing with safety to
humans, only one species is being
protected and extrapolations are made
far outside the limits of the actual test
results, such as to 1 death in 100,000
people. With aquatic life, numerous
species need to be protected and
extrapolation far beyond the actual data
is not readily accepted. In addition,
safety or uncertainty factors are more
readily accepted when protecting people
than when protecting aquatic organisms.
Most aquatic lexicologists are not
willing to.let criteria for the protection
of aquatic life be as dependent on,
mathematical models, assumptions, and
manipulations as on the actual test
results. Most people with experience in
aquatic toxicology have an intuitive
"feel" about how data should be
interpreted and the Guidelines are
merely an attempt to formalize a
resaonable approach. The Guidelines
could be written as mathematical
algorithms and some approach such as
error models could be developed in
order to derive confidence limits.
However, the algorithms and models
would contain many unproven
assumptions and, to be worthwhile.
would undoubtedly require more data
than are usually available. Although
such models and algorithms would be
acceptable to many statisticians and
may be an appropriate future goal, the
current Guidelines need to be uscoble
by and comprehensible to current
aquatic lexicologists. Most experienced
aquatic lexicologists will judge the
reasonableness of any set of Guidelines
by comparing the resulting criteria for
various pollutants with the data
available for those pollutants using a
"common sense" interpretation of data.
30. Comment—The Guidelines should
not use unsound statistical procedures
or misuse sound statistical procedures.
Response—EPA has tried to make
sure that no statistical procedures are
misused in the Guidelines, that no
unsound stalislical procedures arc used,
and that the purposes of the calculations
are explained adequately.
31. Comment—It appears that
geometric means were used instead of
arithmetic means in the Guidelines to
obtain lower values.
Response—Decisions such as this
were made throughout the Guidelines on
a case-by-case basis, and none were
based on whether the resulting criteria
would be higher or lower. The selection
of the procedure used to calculate the
mean could be based on the distribution
of the values in the individual data set.
Unfortunately, with small data sets
rarely is it possible to reject many
possible distributions and with large
data sets all possible distributions are
often rejected. Because many of the data
sets of interest in the Guidelines are
small, a reasonable approach is to base
the selection of a procedure for
calculating the mean on some general
principles such as:
a. Sets of ratios and quotients are
likely to be closer to lognormal than
normal distributions. Thus geometric
means, rather than arithmetic means,
are used for acute-chronic ratios and for
bioconcentration factors. '.
b. When there are numerous
independent possible sources of error
for each datum In a set, the error tends
to be multiplicative rather than additive.
Thus when the acute or chronic toxicity
of a substance to a particular species is
determined; in different laboratories
using different batches of organisms,
different waters, etc, the geometric
means should be used to calculate the
species mean value rather than the
arithmetic mean.
c. If a set of numbers approximates a
lognormal distribution, the logarithms of
the numbers will approximate a normal
distribution.
d. The distribution of the sensitivities
of individual organisms in a toxicity test
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is likely to be closer to a lognormal
distribution than a normal distribution.
Thus the geometric mean, rather than
the ari theme tic mean, of the upper and
lower chronic limits is used.
32. Comment—There should not be
any, criteria which apply to all bodies of
water. Criteria should be specific for
Individual states, regions, other
geographic areas, or bodies of water.
Response—The Guidelines are
designed to provide guidance In the
collection and Interpretation of data
concerning the effects of pollutants on
aquatic life and its uses. The uses of the
resulting criteria will be described by
EPA in various regulations. If desired,
the Guidelines can be appropriately
modified and used to derive a criterion
specific to one or more bodies of water
or geographic areas if an appropriate
data base is available. The critical
literature reviews on which the criteria
are based will be available for use In the
derivation of local, state, or regional
criteria. The latitude allowed for
deriving local, state, or regional criteria
and standards will be determined by the
implementation policy presently being
developed by EPA.
33. Comment—The Guidelines should
result in criteria that are specific for
individual species or groups of species
(e.g.. warmwater and coldwater).
Response—If the necessary data were
available, criteria could be derived for
any particular species or group of
species. It was Impractical for EPA to
derive criteria for many such groups, but
a relatively simple division is freshwater
and saltwater organisms because these
two groups rarely coexist Most other
possible general divisions of species are
faced with the problem that species
coexist in various combinations unless
the groups are very harrow. In addition,
toxicity data are rarely available for -
very many individual species and so
data for representative species must be
used, unlasa appropriate new data are •
generated. Also, the available data
sometimes show wide differences within
families so extrapolations from one
species to another are often tenuous.
Because of these problems, deriving
criteria for individual species or groups
of species was deemed impractical.
34. Comment—A criterion should be
one number, not two.
Response—The two-number criterion
is an acknowledgement that aquatic
organisms can tolerate short exposures
to concentrations that are higher than
those they can tolerate continuously. In
a two-number criterion, the higher
number can assure that short-term
fluctuations above the average are not
too high, whereas the lower number can
assure that the long-term average is not
too high. A one-number criterion could
be derived by using the existing 24-hour
average as an instantaneous maximum.
This would certainly provide additional
protection, but would provide
unnecessary overprotection in most
cases. Because a one-number criterion
would be more of an approximation
than a two-number criterion, one-
number criteria would be too high or too
low more often and to a greater degree
than two-number criteria.
35. Comment—The criteria should not
specify sampling schemes.
Response—Criteria should state
numerical concentration limits in terms r
of exposure durations because,
everything else being constant the
amount of adverse effect depends on
both the concentration of the pollutant
' and the duration of exposure. Criteria in
the Green Book, Blue Book, and Red
Book were usually stated as single
numbers with no duration expressly
stated. The implication was that the
criteria were never to be exceeded at
any time. Each criterion was apparently
and instantaneous maximum. In
practice, however, standards derived
from these criteria were usually
enforced on the basis of 24-hour
composite samples. To avoid any
ambiguity, the Guidelines specify that a
criterion should be explicitly stated in
terms of two time frames: an
instantaneous maximum and a 24-hour
average. However, this is not a
specification for a sampling scheme.
Standards developed from such a
criterion should probably specify a
sampling scheme for compliance
monitoring, but it would not necessarily
be in terms of point measurements and
24-hour averages.
Any sampling scheme used to
determine whether or not an ambient
concentration exceeds a water quality
criterion or a comparable water quality
• standard should take into account such
things as the ratio of the instantaneous
maximum and the 24-hour average and
the retention time of the body of water
because these will primarily determine
which portion of the criterion is most
limiting in any specific situation. The
sampling scheme should probably also
take into account the cost of the
analyses and results of any past .
analyses.
36. Comment—The criteria should be
stated in terms of time frames longer
that an instantaneous maximum and a
24-hour average.
Response—These two time frames
were chosen because they would allow
the derivation of a criterion which
would be less restrictive than, but just
as protective as, the previous one-
number criterion. These two specific
time frames were chosen because they
match two kinds of samples that are
commonly collected: grab samples and
24-hour composite samples. THese
specific time frames could probably be
changed somewhat without much
practical effect but EPA saw no
particular advantage to anyone to
introducing novel time periods. For
example, for all practical purposes in
most situations a 10-minutes average is
probably about the same as an
instantaneous maximum.
Large increases in the time frames,
however, would not provide the same
amount of protection. If the
instantaneous maximum were changed
to a 24- or 98-hour average, and the 24-
hour average were changed to a 7- or 30-
day average with no change in the
numerical limits, the amount of
protection afforded aquatic life would
fall to an unacceptable level. The longer
the time span for the average, the higher
the instantaneous concentration could
be for short periods of time within that
span. Although most chronic tests last
for 28-days or longer, some chronic
effects may be caused by short
exposures of sensitive life stages. If the
acute-chronic ratio is small fluctuations
in the instantaneous concentration may
even cause acute toxidty, especially for
cumulative pollutants, because for some
substances the 24-, 48-. and 98-hour
acute values do not differ too much.
37. Comment—A two-number
criterion will be difficult to enforce.
Response—Criteria'are not
enforceable. Standards are enforceable.
When standards to protect aquatic life
are developed, they may or may not be
in the same format as the criteria for
aquatic life. Few standards are
adequately enforced because of the high
cost of continuous monitoring. The real
value of many criteria and standards is
in the design of waste treatment
facilities; a two-number criterion should
be a better basis for design than a one-
number criterion.
38. Comment—The criteria should be
expressed to one significant figure, not
two.
Response—EPA acknowledges that
there is much variability in some of the
data and that the range of sensitivites is
often great When the requirements of
the minimum data base are satisfied and
the data agree reasonably well, two
significant figures are not unreasonable.
Rounding off to one significant figure
could arbitrarily raise or lower the
criterion by up to forty percent with no
apparent consistent benefits to
dischargers, regulators, or aquatic life.
39. Comment—The Guidelines should
only use data for species that ought to
be protected.
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79363
Response—In order to protect
commercially and recreationally
important species, a wide variety of
"unimportant" species must also be
protected. Such so-called "unimportant"
species include the food organisms all
the way to the bottom of the food chain.
The "important" species in an aquatic
community cannot maintain themselves
without the help of primary producers,
primary consumers, nitrlfiers,
dentrifiers, detritivores and saprophytes.
40. Comment—Criteria should not be
based on sensitive, short-lived-
invertebrates. \
Response—Many species of
invertebrates are short-lived and are not
widely distributed. However, these
numerous short-lived, local species do
serve important functions and should be
represented In the data base. This group
of organisms needs to be protected even
if no one species can be considered
important.
41. Comment—Criteria should protect
endangered species. -
Response—EPA agrees that criteria
should protect endangered aquatic
species. However, very few toxicity
tests have been conducted with
endangered species, and it does not
appear feasible to require tests with
such species. Endangered species are
some of the many untested species
which should be protected by criteria
derived from available data using the
Guidelines.
42. Comment—Migratory species are a
special problem.
Response—Migratory species should
usually be protected by criteria derived
using the Guidelines unless such species
are unusually sensitive. Migratory
species may be especially susceptible to
avoidance, but few data are available to
compare species on this basis.
Avoidance may be a serious latent
problem because it might apply to all
motile species, rather than just
migratory species, and it has not been
studied very much.
43. Comment—Estuarine species were
ignored.
Response—The term "saltwater
organisms" is meant to include estuarine
species as well as true marine species.
44. Comment—The classification
"invertebrates" includes species that are
too dissimilar to be grouped together.
These species should be separated into
phyla or classes.
Response—The never-ending
arguments between the "lumpers" and
the "splitters" can only be resolved by
considering the advantages and
disadvantages of each approach in each-
situation. The "splitters" can usually
argue that obvious differences should be
taken into account and it is certainly
true that shrimp are different from
insects and both are different from
worms. It can also be argued that there
are significant differences within phyla,
classes, and families. Each species could
be considered a separate group, if
differences between stains are
arbitrarily ignored. After the species are
split into separate groups, the problem
then would be whether to recombine the
data to derive one criterion for all
species or to derive one criterion for
each group. If numerous criteria are
derived for a pollutant, how are these to
be used to develop standards? Another
problem is that unless more data are
generated, the greater the number of
groups, the less information there is
available per group.
The basic question is "What are the
important differences that need to be
taken into account and how should this
be done?" Because there are differences
between taxonomlc groups, the
Guidelines require data on a number of
species from a varitety of taxonomic
groups. The information of each
separate species is treated individually.
This approach preserves the differences
between species and allows all species
to be considered in the development of
the criterion. The number of data points
is increased and the range of the data is
readily apparent Because
"invertebrates" is already a large
diverse group and because the range of
sensitivities of fish usually overlaps that
of invertebrates, little justification exists
for not combining all aquatic animals.
45. Comment—Do not extrapolate
from freshwater organisms to saltwater
organisms or vice versa.
Response—Criteria and absolute
toxicity values were not extrapolated
from fresh water to salt water, but some
relative data were, when it did not
appear that factors such as salinity
affected the data. The toxicity of some
substances apparently is significantly
affected by salinity, but most substances
seem to have overlapping ranges of
toxicity to freshwater and saltwater
organisms. However, because these two
kinds of organisms rarely inhabit the
same body of water simultaneously,
separate criteria were derived for each.
Even though these two kinds of
organisms are physiologically different.
they do not seem to be too different •
lexicologically. Bioconcentration factors
and acute-chronic ratios seem to be
fairly similar for many freshwater and
saltwater species for many pollutants.
particularly organic chemicals.
46. Comment—The Guidelines base
the criteria only on sensitive species and
do not take into account insensitive
species.
Response—The Guidelines do not
necessarily base the criteria on the data
for the most sensitive species. However,
an aquatic ecosystem cannot be
protected by protecting only the species
which are insensitive. Protecting half the
species will probably not protect the
community. To offer reasonable
protection to aquatic life and its uses.
each major kind of organism and each
major use must be given reasonable
protection. In some cases it may in fact
be necessary to protect the most
sensitive species if it is a highly
desirable species.
47. Comment—Species should be
tested at their environmental extremes.
Response—Toxicity tests with each
pollutant could .indeeed be conducted
with some or all species under a variety
of extreme conditions and the lowest
result obtained with a species could be
used instead of a mean result On the
other hand, differences between results
with different species seem to be much
greater, and therefore more important,
than the differences between results
obtained with one species under
different conditions. Furthermore,
criteria need not necessarily protect
species from all stress under the most
extreme conditions, because aquatic
communities and populations of
individual species can recover from
some perturbations.
48. Comment—Only data for species
that are widely distributed.
representative, critical, indigenous, '
important, ecologically relevant and
sensitive should be used.
Response—Few species would satisfy
all of the requirements that have been
suggested. As more and more data are
obtained with a wider variety of species
for any one pollutant, it becomes more
obvious that few if any species are
atypically sensitive, although that may
not be true for aquatic communities
which contain very-few species. No data
exist to show that species in any one
key role are lexicologically more
sensitive than other kinds of species.
Ecologically relevant species and
species that have key roles or are
relevant to the overall functioning of
viable ecosystems are not necessarily
lexicologically different from other
species. EPA feels that if the available
data cover an adequate number and
variety of species, it is not necessary to
try to identify and conduct tests with all
important, sensitive species. In addition,
the derivation of a criterion should not
be based only on sensitive species,
because a knowledge of the range of
sensitivities may be useful. For instance.
elevated concentrations of a pollutant
that produces a narow range of species
sensitivities are likely to cause more
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damage than elevated concentrations of
a pollutant that produces a wide range
of species sensitivities.
49. Comment—The distinction
between Icnizable and unionizable
compounds is not very good because
some chemicals ionize and reach
chemical equilibrium very slowly and
others very rapidly.
Response—Most chemicals can .
readily be classified Into one of three
groups:
A. Chemicals that ionize, including
hydrolyze, at least 90% and reach 90% of
equilibrium in less than 8 hours in most
surface waters.
B. Chemicals that ionize, including
hydrolyzfe, less than 10% in 30 days in
most surface waters,
C. Chemicals that do not fit into either
one of the above categories.
For the purpose of the Guidelines,
chemicals hi the A group should be
considered ionizable, chemicals in the B
group should be considered non-
ionizable, and chemicals in the C group
should be classified on a case-by-case
basis. Although the distinction between
ionlzabls and unionizable may not be
perfect, It is very useful for most
chemicals.
SO. Comment—Each individual
organic compound should be considered
separately.
Response—The vast majority of
organic chemicals will be considered
separately according to the Guidelines
except for structurally similar organic
compounds that meet all three
specifications given in the Guidelines,
such as polychlorinated biphenyls and
toxaphene.
51, Comment—In-stream water
quality criteria are meaningless for
substances lhat are highly insoluble.
Response—The concentration of some
substances in sediment may be
important separate from the
concentration of the substance in the
ambient water and for these compounds
a sediment quality criterion may be
necessary. Generally such compounds .
can also cause adverse effects if the
concentration in the ambient water is
too high even if the concentration in the
sediment is low. Thus for such
compounds both kinds of criteria may
be necessary rather than just one or the
other.
52. Comment—If a substance is not
dissolved, it is not biologically or
lexicologically available.
Response—Although this may usually
be true, it certainly does not apply to
elemental mercury which can be
oxidized and methylated to form a very
toxic compound. Some organic acids
and phenols and hydroxide and
carbonate salts of metals have
solubilities which differ substantially
from one body of water to another.
53. Comment—Criteria for metals
should not be for total metal.,
Response—Criteria for metals will
generally not be based on total metal.
Most will be based on total recoverable
motal because forms of metals that are
not measured in the total recoverable
procedure probably are not, and will not
become, toxic. A major problem is that
some people use a procedure for total
recorverable, but report the results as
total, metal. In many situations the two
results are about the same, but in some
cases the results are quite different, •
54, Comment—The Guidelines should
give .more guidance for distinguishing
between acceptable and unacceptable
data.
Response—The Guidelines contain as
much detail on this subject as EPA
believes is currently feasible. Items such
as the maximum acceptable control
mortality and minimum number of test
organisms are based on what many
aquatic lexicologists generally feel are
acceptable, as expressed in published
methods. No data should be used in the
derivation of a criteria until their quality
and acceptability had been reviewed by
a competent person. Competent people
will occasionally disagree, but that is. a
fundamental property of subjective
decisions.
55, Comment—Only published data .
should be used.
Response—Peer review is one of
many concepts that is better in theory
than in practice. Some poor quality data
are published and some high quality
data are rejected. In addition,
publication is not a particularly rapid
process. Whether or not data are used
should depend on the applicability and
quality of the data, not on whether they
have been published. Data that are not
published should be made readily
available if they are used to derive
water quality criteria.
SB. Comment—All static test are
unacceptable
Response—In general, high quality
flow-through acute tests are preferable
to high quality static acute tests, but
static tests are by no means
unacceptable. Few data are available to
show whether static tests consistently
produce acute values lower or higher or
different than flow-through tests,
Whereas degradation, violatilization.
and buildup of metabolic products are
more likely to be a problem in static
tests, operator and mechanical errors
are more likely in flow-through tests.
Static acute tests are certainly not
unacceptable for most pollutants, but
static chronic tests generally are
unacceptable because of changes in the
toxicant concentrations and' the quality
of the dilution water during the test.
57. Comment—Data obtained, using
test organisms that were previously
exposed to the pollutant should be used.
Response—Comparisons of results
obtained with unexposed and previously
exposed organisms should indicate:
whether or not acclimation has .
occurred. Generally, data obtained with
acclimated organisms should not be
used in deriving criteria because
acclimated organisms are the exception
rather than the norm. Rarely, If ever, can
acclimation be depended on to protect
organisms in a field situation because
concentrations of ten'fluctuate and
motile organisms do not stay in one
location very long. Data obtained with
acclimated organisms may be
acceptable for use in deriving some site-
specific criteria.
58. Comment—Foreign species should
be used to expand the data base.
Response—Foreign species may be
representative of indigenous species, but
some of them are quite unusual. Data
obtained with foreign species may give
good indications of indigenous speceis
that should be used in tests on some
pollutants and may identify some
potential problems that should be
investigated.
59. Comment—-If data for brine shrimp
are not used, the criteria should not
apply to saline waters.
Response—Data obtained using brine
shrimp are not used because these
organisms are atypical. Although they
may not be usually sensitive or
insensitive to various pollutants, the
species found in North America and
used for testing only survive in the Great
Salt Lake and in salt ponds near San
Francisco Bay. These two habitats are
unlike any others in the United States. If
criteria were to be derived specifically
for the Great Salt Lake or for salt ponds,
then data for brine shrimp should be
used.
60. Comment—Structure-activity
relationships should not be used unless
proven.
Response—No provision Is made in
the Guidelines for the use of structure-
activity relationships. Such relationships
may soon be well enough understood
that they can be used in deriving water
quality criteria.
61. Comment—A criterion should not
be derived for a pollutant until data are
available for a broad range of
commercially, recreaiionally, and
ecologically important species. Each
species should be acutely and
chronically tested under a variety of
conditions in a number of different
waters.
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79365
Response—Except for those people
who merely want to stop EPA from .
deriving any water quality criteria, most
people will admit that there must be
some reasonable limit as to how much
information is necessary concerning any
regulatory action.This is as true for
deriving water quality criteria, as it is
for issuing NPDES permits, submitting
PMNs, registering pesticides, etc. All of
these regulatory activities deal with
potentially significant adverse effects on
aquatic organisms and should take into
account many of the same possible
kinds of adverse effects. Therefore, the
data needs for these various activities
should probably be somewhat similar,
but for each regulatory activity the
minimum data requirements also need
to take into account the special aspects
of the program and practical
considerations. Unrealistic data
requirements will benefit no one. It is
not necessary that all questions be
answered before any action is taken. It
is only necessary that enough data be
available to allow reasonable
confidence that the water quality
' criteria will generally not be too high or
too low.
EPA has developed minimum data
requirements that describe the amounts
and kinds of information that should
usually be available if a criterion is to
be derived using the Guidelines. When
the minimum data requirements are
satisfied, it should usually be possible to
derive a useful criterion. The
requirements take into account many
things such as:
a. The existence of some species
which are commerically or
recreationally important and generally
sensitive to some broad classes of
pollutants;
b. The range of species for which data
are available;
c. The cost of obtaining additional
data and the usefulness of the data; and
d. The reasonableness of
extrapolations from one species to
another within and between groups.
The requirements set forth in the
minimum data base are indeed minimal,
considering the great varltey of species
which exist in most aquatic ecosystems.
However, EPA feels that based on the
availavble information the routine
requirement of more data would
probably not improve criteria enough to
justify the additional cost.
62. Comment—The mimlmum data
requirements should depend on the
nature of the pollutant.
Response—EPA feels that such an
approach may be feasible some time in
the future, but would be an unwarranted
level of sophistication at this time. Fora
few pollutants, it may be possible to
relax some of the data requirements, but
in general this can only be determined
after enough data are available to
indicate that a special case exists. In
other cases the minimum data may
indicate that additional data are highly
desirable.
63. Comment—Criteria should not be
derived if enough data are not available.
The alternative procedures which were
proposed should not be used.
Response—EPA agrees that a
numerical criterion should not be
derived if enough appropriate data are
not available, except in some special
cases. EPA also agrees that the
alternative procedures which were
proposed should not be used to develop
numerical criteria at the present time.
However. EPA feels that when a
numerical criterion is not derived, a
descriptive criterion can be used to
accurately reflect the latest scientific
knowledge.
64. Comment—The guidelines should
give more guidance on relating a
criterion to a water quality
characteristic.
Response—More detail on this subject
has been written into the Guidelines.
65. Comment—If data on the relation
of toxicity and water quality are not
available, no criterion should be
derived.
Response—The purpose of a criterion
is to present the best available
information, not to ensure that all
desirable.information is available. Any
water quality characteristic may affect
the toxicity of each pollutant to some
degree and it is never going to be
possible to investigate all such
interactions for even a few species and
pollutants. EPA has adopted a minimum
data base requirement for deriving a
criterion, but there must be practical
limits or no criterion will ever be
possible. When the minimum data base
requirements'are satisfied, a criterion
should be derived regardless of
speculation that some unstudied
relationship exist. When enough good
data demonstrate a relation between
toxicity and a water quality
characteristic, an attempt should be
made to use this information in the
derivation of a criterion. A major
purpose of site-specific criteria is to take
into account the effect of local water
quality conditions on toxicity.
66. Comment—Do not specify the form
that a relationship between toxicity and
water quality must take.
Response—The Guidelines allow the
use of any set of transformations that fit
the data well. The log-log model is given
as an example.because it seems to fit
most of the available data concerning
the relationship between hardness and
toxicity of metals (the only such
relationship for which much quantitative
data are available] reasonably well.
87. Comment—The toxicity of metals '
should not be related to "hardness".
Response—EPA has tried to derive
criteria in a form that will (a) adequately
protect aquatic Organisms and (b) be
practically useful. Hardness is used as
an easily measured surrogate for a
number of interrelated water quality
characteristics, such as pH, alkalinity,
calcium, and magnesium. Various
combinations of these probably affect
individual metals differently, but these
are all reasonably well correlated with
hardness in a wide variety of natural
waters. Some waters, such as those
impacted by acid mine drainage.
obviously are special cases, but they
have special problems of their own.
68. Comment—Do not extrapolate
slopes for toxicity vs. water quality from
fish to invertebrates or from acute
values to chronic values.
Response—The Guidelines do not
now assume that the acute slope and the
chronic slope are similar for a pollutant.
On the other hand, there is no reason to
believe that invertebrates are more
similar than are fish and invertebrates.
As explained earlier, the group
"invertebrates" does not consist of a
collection of species that are similar
taxonomically or lexicologically. Some
water quality characteristics apparently
affect the toxicity of the pollutant, rather
than the sensitivity of the organisms. For
these kinds of factors, slopes should be
the same for different species. Even
factors that affect such things as the
permeability of membranes may
produce similar slopes for a wide
variety of species. If each species must
be treated separately, no criteria will
ever be possible.
69. Comment—Relationships based on
only two points should not be used.
Response—Two points certainly do
not provide very much information
about-the shape, slope and position of a
line. However, if other information or a
reasonable assumption is available
concerning the shape of the line, two
good data points, spaced at a
reasonable interval, can provide very
useful information concerning the slope
and position of the line. Three
appropriately spaced points would
certainly be better, and four points
would be an Ideal minimum.
70. Comment—Do not combine
relationships that are and are not
statistically significant.
Response—The Guidelines do now
specify that relationships should be
tested for statistical signficance. A test
for statistical significance may be one
indication of whether or not a slope is
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Federal Register / Vol. 45. No. 231 / Friday. November 28, 1980 / Notices
useful, but such a test canr.ot be used
with just two points and does not take
into account such things as the
comparability of the data, the quality of
the test and the range of the
independent variable. A relationship
based on six points may rot be as
significant as i! seems if five of the
points are tightly grouped.
71. Comment—The Guidelines should
not combine 96-hr LG50 values and 48-hr
EC50 values.
Response—Both LC50 values and
EC50 values are used to measure acute
toxicity of a substance to aquatic
organisms. In general, an ECSO can be
based on a wide variety of effects, but
the Guidelines specify that the only
effects to be used for deriving criteria
are incomplete shell development.
immcbilization. and loss of equilibrium.
AU of these are certainly drastic effects.
In a field situation these effects
probably often lead to death. Jnst as lie
endpoint may be specific for the species,
so may be the length of the test. The
generally accepted length of an acute
test with daphnids Is 48 hours, whereas
for most species of fish, it is 96 hours.
Thus the Guidelines use both 48-hr ECSO
values and 98-hr LC50 values because
they are the widely accepted durations
and endpoints used to measure acute
toxicity to specific species.
72. Comment—Shell deposition tests
are chronic tests and should not be
equated with lethality tests.
Response—"Acute" implies "short"
not "death". Many acute toxicity tests
do use death for the effect, but many
also use non-lethal effects. The shell
deposition test is one of many non-lethal
acute tests and is generally accepted as
a short test compared to the average life
span of oysters.
73. Comment—Adjustment factors
should not be used to adjust for the
length of the test, the technique, and
unmeasured concentrations.
Response—All three kinds of
adjustment factors have been deleted
from the Guidelines. The factor for the
length of the test was found to be
unnecessary because most tests had
been conducted for the standard times
usually specified for the individual
species. Thus the Guidelines now
specify that only data from tests
conducted for the time specified for the
species should be used to calculate the
Final Acute Value.
EPA has found that on the average
flow-through acute tests give results
slightly lower than do static tests, but
the relationship does not seem to be too
consistent and may vary from species to
species for some pollutants. In addition,
on the average results based on
measured concerntrations do not seem
to be much different from those based
on unmeasured concentrations.
However, the results of flow-through
tests based on measured concentrations
are generally accepted as being better
measures of acute toxicity than the
results of flow-through tests based on
unmeasured concentrations or the
results of any static or renewal
tests.Thereforc. whenever the results of
flow-through acute tests in which the
concentrations were measured are
available, the results of all other kinds
of acute tests with that species and
pollutant are not used in the calculation
of the species mean acute value.
74. Comment—Species sensitivity
factors should be pollutant-specific; and
average factor should not be calculated
for a variety of substances.
Response—EPA agrees. The
requirement for acute values for at least
eight different species was developed in
part to allow for a reasonably good
calculation of a mean acute value and a
species sensitivity factor for each
individual pollutant. A better way of
using the acute values for the individual
species has been developed, but no
extrapolations are made from one
pollutant to another.
75. Comment—The distribution of
species mean acute values for a
pollutant will be truncated if the species
cannot be killed or affected by
concentrations above solubility.
Response—Some species are so
resistant to some pollutants that they
cannot be killed or affected in acute
tests even by concentrations which are
much above solubility. Such "greater
than" values cannot be used in the
calculation of means and variances for
pollutants. When the "greater than"
values are for insensitive species and
are at or above solubility, the values can
be used in the calculation of the Final
Acute Value by adjusting the cumulative
proportions for all the spelces with
quantitative values. The shape of the
curve at the high end cannot be
determined, but the Final Acute Value is
more dependent on the species mean
acute values and the cumulative
probabilities at the low'end.
76. Comment—Early life-stage tests
with fish should be used
interchangeably with life-cycle and
partial life-cycle tests with fish.
Response—EPA agrees that early life-
stage tests with fish generally give about
the same results as comparable life-
cycle and partial life-cycle testa.
However,Nbecause the shorter test is
merely a predictor of the longer tests,
whenever both kinds of results are
available, the results of life-cycle and
partial life-cycle tests should be used
instead of the results of oariv life-stage
tests.
77. Comment—Appropriate measures
of chronic toxicity and appropriate
lengths of exposure should be defined.
Response—The descriptions of
appropriate chronic tests have been
clarified.
78. Comment—The factor of 0.44
should not be used.
Response—It is not now used.
79. Comment—The Final Chronic
Value should not be lower than the
lowest measured species chronic value,
even if chronic data are not available
for sensitive species.
Response—Aquatic ecosystems
cannot be protected from chronic
toxicity by protecting only the
insensitive species from chronic toxicity.
In the past both arbitrary and
experimentally determined application
factors have been used to relate acute
and chronic toxicity. For a variety of
reasons the Guidelines do not use an
application factor, but instead use the
acute-chronic ratio, which is similar to
the inverse of an application factor.
Thus the acute-chronic ratio should
normally be greater than one. The acute-
chronic ratio is to be used with
invertebrates as well as fish and is to be
an experimentally determined value for
each individual pollutant The acute-
chronic ratio should also avoid the
confusion as to whether a large
application factor Is one that is close to
unity or one that has a denominator that
is much larger than the numerator. The
acute-chronic ratio is calculated by
dividing the appropriate measure of
acute toxicity for the species (as
specified in the Guidelines) by the
appropriate measure of chronic toxicity
for the same species (as specified in the
Guidelines).
Some people have confused
application factors and safety factors
and use of the term "acute-chronic
ratio" should help avoid this problem.
Acute-chronic ratios are a way of
estimating the chronic sensitivity of a
species for which no chronic toxicity
data are available. Safety factors would
provide an extra margin of safety
beyond the sensitivity of the species.
Safety or uncertainty factors are
intended to reduce the possibility of
underprotection, whereas acute-chronic
ratios are intended to estimate the
actual chronic sensitivity of the species
to the pollutant. This estimate is just as
likely to be too high as it is to be too
low. A mean acute-chronic ratio will in
fact be too high for half the species and
too low for the other half.
When three or more acute-chronic
ratios have been determined for a
pollutant with both fish and
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79367
-.vertebrates, three patterns have been
ibserved when the individual species
ire listed in order of their species mean
cute values:
a. The ratios randomly differ by a
actor'of ten or more.
b. The ratio appears to be about the
ame (within a factor of ten) for all
pecies. .
c. Species with higher acute values
ilso have higher acute-chronic ratios.
The available data indicate that fish
ind Invertebrates do not consistently
lave different acute-chronic ratios and
hat for some pollutants freshwater and
saltwater species have similar acute-
:hronie ratios.
80. Comment—No application factor
hould be used unless it is specific for
he pollutant, species, and water.
Response—There la no point in using
in application factor or acute-chronic
atio or any concept if It does not allow
•ome generalization or extrapolation
rom one species to another or from one
vater to another. Not allowing'any
jeneralizations or extrapolations would
equire that much data be generated for
>ach species and each pollutant in each
valer in which a criterion is necessary.
When enough supporting data, are
ivailable, extrapolations using such
hings as acute-chronic ratios are cost-
iffective and scientifically sound.
81. Comment—Additional
levelopment of methodology for toxicity
ests with aquatic plants is needed:
Response—This is most certainly true.
vluch other research also Is needed, and
;enerally is considered higher priority.
ZPA. hopes that someday all of the
iddltional research that needs to be
lone will be done. Few pollutants seem
o affect aquatic plants at
-.oncentrations which do not chronically
iffect aquatic animals, and it is hoped
hat this is not an artifact of the test
nethods currently used.
: 82. Comment—Data on toxicity to
ilants should not be used for deriving
•jiteria because plants are more site-
specific than animals.
Response—Numerous species of
itants, especially algae, exist in most
lodies of water. On the other hand, EPA
uiows of no data! to support the
:ontentioh that the sensitivities of
iquatlc plants are any more site-specific
han those of aquatic animals, or that
: he range of sensitivities between plants
s as great as that for animals. One
species may or may not be
epresentative of other species. After the
nethodology for toxicity tests with
iquatic plants is better developed, tests
vith a wider variety of species would
:ertainly be desirable.
83. Comment—The Final Plant Value
ihould not be the lowest available plant
value based on measured
concentrations.
Response—EPA adopted the
procedure described in the Guidelines
for obtaining the Final Plant Value for
several reasons including:
a. The methodology for toxicity tests
with aquatic plants is not well
developed.
b. For only a few pollutants have
toxicity tests been conducted with more
than a very few species of plants.
c. Little Is known about the range of
sensitivities of various species of
aquatic plants.
d. Based on available data, almost no
pollutants are toxic to aquatic plants at
the lowest concentrations which are
chronically toxic to aquatic animals or
cause unacceptable residues.
84. Comment—Residue accumulation
in any part of an aquatic ecosystem
should be prevented as much as
possible.
Response—Accumulation of residues
in aquatic organisms only becomes a
problem if the concentration of residue
is high enough to adversely affect either
(a) the organism itself, (b] a consumer of
the organism, or (c) the'marketability of
the organism. Adverse effects on the
aquatic organism itself will be detected
in acute and chronic toxicity tests. The
use of FDA action levels and chronic
feeding studies with wildlife are
designed to protect the uses and
consumers of aquatic organisms.
85. Comment—Bioconcentration
factors (BCFs) derived from field data
should not be used.
Response—EPA feels that BCFs
derived from adequate data, whether
they be laboratory data or field data,
should be used. More data are
necessary to document a BCF from a
field exposure than a laboratory
exposure, as specified in the Guidelines,
but if enough data are available, field
BCFs should be used.
86. Comment—Kinetically derived •
bioconcentration factors (BCFs) should
be used.
Response—Kinetically derived BCFs
should be used if the bioconcentration
test lasted long enough, i.e., to .apparent
steady-state, to verify that the model
(assumptions) used in the calculations
actually fits the data for the individual
pollutant.
87. Comment—Bioconcentration
factors (BCFs) should not be estimated
from octanol-water partition
coefficients.
Response—The available data seem
to indicate a reasonably good
relationship for lipid-soluble substances
between steady-state BCFs and octanol-
water partition coefficients. BCFs
estimated from partition coefficients are
not used in the Guidelines because
measured BCFs are available for all
pollutants for which a maximum
permissible tissue concentration is
available.
88. Comment—Bioconcentration
factors (BCFs) are dependent on
temperature, food, salinity, stress, and
other things.
Response—Many things such as these
probably do affect BCFs. Until data are
available to show that such effects are
important and are not species-specific.
little needs to be, or can be. done to take
such factors into account when deriving
water quality criteria.
89. Comment—Bioconcentration
factors (BCFs) should be based only on
tissues that are actually eaten.
Response—Although people usually
only eat muscle tissue of fish, wildlife
usually eat the whole body of fish. The
tissues used in the determination of
BCFs must be appropriate to the kind of
consumer organism or regulatory action.
On the other hand, since the BCF for a
lipid-soluble substance seems to be
proportional to percent lipids;
extrapolations can be made on the basis
of percent lipids regardless of the tissue.
90. Comment—Chronic toxicity tests
with rats and mice should not be used
as representative of tests on mammalian
wildlife.
Response—Because results of tests on
a variety of species are extrapolated to
man, it should be just as reasonable to
extrapolate from one mammalian
species to another mammalian species
within certain limits. However, such
extrapolations are not now used in the
Guidelines; only the results of chronic
toxicity tests with wildlife are used to
protect wildlife consumers of aquatic
life.
91. Comment—Information concerning
bioconcentration should only be used if
such information is used to protect
aquatic organisms, not to protect the
marketability of aquatic organisms.
Response—Protection of aquatic
organisms must include not only the
protection of the existence of aquatic
organisms, but also protection of the
common uses of aquatic organisms.
Commercially important aquatic
organisms cannot be considered
adequately protected if they cannot be
sold. The Guidelines do not use any
data pertaining to safety to humans in
an attempt to protect human consumers
of aquatic organisms. Instead, the
Guidelines merely attempt to ensure
that residues in aquatic organisms do '
not exceed FDA action levels so that the
uses of commercially and recreationally
important species are not restricted by
the Food and Drug Administration.
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92. Comment—A Final Residue Value
calculated from an FDA action level is
actually a concentration that will result
in the average concentration in some
species being at the FDA action level.
Response—This is a good point. A
similar situation exists when the
calculation is based on a concentration
which caused an adverse effect in a
chronic wildlife feeding study. In all
such cases, the Final Residue Value
should be lower, but EPA knows of no
non-arbitrary way to determine how
much lower the value should be.
93. Comment—The FDA action levels
for finished animal feed should not be
used, .
Response—They are not now used.
94. Comment—Flavor impairment
should not be used to derive water
quality criteria for aquatic life.
Response—Many of the commercially
and recreatlonally important aquatic
orgnaisms are consumted by people. If
the flavor is significantly impaired, the
use of these species will be adversely
affected. Flavor impairment should be
considered an effect that can adversely
affect the use of aquatic organisms.
95. Comment—The Instructions for
using the other data are not very
detailed and are not mathematical.
Response—EPA has tried to include
as much detail in the instructions for
using the other data as are currently
justified. Extensive detail and
mathematical treatment are not deemed
realistic at this time because so little
information is available concerning the
various kinds of other data.
90. Comment—The final review of the
criteria should allow revision up or
down based on sound scientific
evidence.
Response—The Guidelines always
have allowed revision up or down, but
this is now stated explicitly in the
Guidelines,
97. Comment—Some bodies of water,
such as some USGS benchmark streams
and the Houston ship channel, contain
concentrations above the criteria for
some pollutants and still contain aquatic
communities that are diverse, healthy,
and productive. Such information should
be used in the review of the criteria
because it indicates that some criteria
are too low.
Response—Rarely are there enough
data available to accurately identify the
concentrations of pollutants to which
aquatic organisms in bodies of water are
actually exposed. The sampling scheme
should provide a good estimate of the
mean and variance of the concentration;
a few grab or composite samples cannot
provide enough information to
characterize the concentrations of
pollutants in most bodies of water. The
concentrations vary not only with time
but also with location at each time, so
the samples must be taken where the
organisms of interest are located at that
time.
A more serious problem concerns the
definition of an acceptable aquatic
ecosystem. How does one determine if
an aquatic ecosystem Is healthy or
productive? If a diverse system is, by
definition, healthy, is it also, by
definition, productive? What is the
minimum acceptable diversity? What is
the minimum acceptable productivity?
Should the acceptable levels of diversity
and productivity be site-specific? Is a
body of water acceptable just because
no dead fish are observed. How many
pounds of trout should a trout stream
produce each year to be considered
healthy and productive? How does one
treat motile species that may avoid
some periodic increases in pollution
levels? Is an aquatic ecosystem healthy
and productive if the normally edible
portion of a consumed species tastes
bad or contains excessive residues?
Questions such as these indicate the
difficulty of quantitatively judging the
quality of aquatic ecosystems on the
basis of their acceptability or usefulness
to man or on any other basis. Although
judging bodies of water would be a
difficult job, it certainly could be done
by a competent group of trained
professionals. The point is that it is not
as easy a job as some people would like
to think. There are also people who feel
that various pristine bodies of water
should be managed because they are not
as productive as they could be.
As mentioned earlier, the criteria
documents derive criteria which may be
too high or too low for some specific
bodies of water. With appropriate
modifications the Guidelines can be
used to derive criteria for any specific
body of water or geographic area. In
addition, it is certainly possible that one
or more factors which affect the toxlcity
of one or more pollutants may not have
been studied very throughly or even
identified yet. The criteria are based on
the best available information and the
state-of-the-art of aquatic toxicology,
but it IB always possible that something
important has not been adequately
studied by regulators, discharges or
academia.
Appendix E.—Responses to Public
Comments on the Human Health Effects
Methodology for Deriving Ambient
Water Quality Criteria
/. Introduction
On March 15.1979, the U.S.
Environmental Protection Agency (EPA)
announced the availability for public
comment of the proposed
for the derivation of ambient
quality criteria for the protection of
human health. The public conitnenti
were resolved in three phases.
First, comments relating to policy
issues were resolved in an initial
screening/disposition by Agency
personnel.' Second, a peer review
workshop was conducted and Involved
•Agency personnel, contractors, and
recognized scientists. The group
evaluated all issues pertaining to the
derivation of criteria for non-
carcinogens, and third, a similar
workshop was held to review all issues
relating to the derivation of criteria for
carcinogens.
The following report presents the
resolutions of the public comments by
the EPA after considering the advice of
the meeting attendees. While the EPA
greatly appreciates the contribution of
these individuals and acknowledges
their substantial assistance in resolving
many difficult questions, the EPA
accepts full responsibility for the
positions outlined in this document.
(Note: Comments addressing similar
issues were appropriately compiled and
summarized under each issue.)
Comments Resolved in Initial Screening
Issue! JJ.,--
Comment summary: The water quality
criteria documents should provide
information and/or guidelines for
deriving standards from criteria.
Response: The water quality criteria
documents contain information which
will be useful in developing standards
(e.g., current levels of exposure).
However, in developing standards,
many additional factors not directly
related to criteria must be considered. It
would be more appropriate to compile
and to analyze this information as part
of the standard-setting process rather
than to Include it In the criteria
documents. Guidelines will be issued
separately since the development of the
standard includes use designation with
a commensurate criteria value.
Issue 2
Comment summary: Water quality
criteria should consider or be limited by
technological achlevability, cost/benefit
analysis, limits of detection, and
environmental fate, .
Response: The distinction between
criteria and standards must be
recognized. For non:carcinogens,
ambient water quality criteria are
estimates of concentrations in water
which will not result in either adverse
human health effects (criteria based on
toxicity) or unplesant taste or.odor
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(organoleptic criteria). For carcinogens.
criteria are estimates of concentrations
of individual compounds in water which
will result in specified increases in the
lifetime risk of developing cancer. By
definition, these criteria exclude
considerations of technological
achievability, .cost/benefit analysis,
limits of detection, and environmental
fate, as appropriate within the authority
of The Clean Water Act (33 U.S.C.
1314(a)]. These factors are more
properly considered in the standard-
setting process.
Issue 3
Comment summary: The validity of a
single criteria for all bodies of water is
questionable. Criteria should be site
specific an/or use specific.
Response: In the standard-setting
process, criteria may be modified based
upon site specific or use specific
considerations.
Issue 4
Comment summary: Even if there is
insufficient data, some criteria must still
be developed for "highly hazardous
compounds."
Response: If there is sufficient
information to indicate that a compound
is "highly hazardous," there should be
sufficient information to derive a
criteria. Conversely, if Insufficient data
are available, by definition no criteria
can be derived.
Issue 5
Comment summary: Criteria should
be derived only for persistent
compounds or for compounds which
present a clear hazard to humans.
Response: Criteria can be derived for
any compound on which sufficient
information is available. By definition.
criteria are independent of persistence
or current levels of exposure.
Issue 6
Comment summary: Criteria should
be developed to protect terrestrial
wildlife as well as humans and aquatic
organisms.
Response: Because of the greet
number of diverse wildlife species and
differences in their habitat, diet, and
behavior, it is unlikely that a single
criteria could be developed to protect all
wildlife species from a given
contaminant. The EPA is currently
assessing possible approaches to
developing a valid methodology for
deriving wildlife criteria. Until a specific
wildlife criteria methodology is
developed, the proposed aquatic life and
luman health effects criteria should
serve as interim levels for the protection
>'• -vldlife.
Issue 7
Comment summary: Criteria should
be derived by an independent scientific
panel and not by the EPA.
Response: The EPA has a legislative
mandate to derive ambient water
quality criteria and must accept the final
responsibility for this process. However,
the EPA has solicited the advice of
many independent scientists in this
effort. It should be noted that the
consensus of the peer review
committees has been considered and
generally followed by the EPA.
Nonetheless, the responsibility for the
criteria rests solely with the Agency.
Issue 8
Comment summary: The ambient
water quality criteria are not sufficiently
protective of special groups at risk.
Response: In most cases, each
document contains a specific section on
special groups at risk. This is intended
to serve as a notice to individuals or
agencies using the criteria; that the
derived criteria may not be sufficiently
protective in all applications. If
sufficient data are available,
information in the section on special
groups at risk could be used to modify
the criteria during the standard-setting
process.
Issue 9
Comment summary: Comments
express concern with the failure of the
criteria to specifically address possible
toxicant interactions.
Response: The importance of toxicant
interactions in the environment cannot
be disregarded. Each document attempts
to summarize the available data on such
interactions. However, since the
composition of toxicants is likely to vary
substantially in different area?, a
general approach modifying criteria
based upon toxicant interactions is not
available at this time. Further, the
limitations of valid approaches for
dealing with interactions in multi-
toxicant mixtures should be recognized.
Issue 10
Comment summary: Because of the
uncertainties involved in deriving
criteria, the criteria should be limited to
only one significant figure.
Response: The number of significant
figures used to express the criteria is an
admittedly arbitrary decision. The EPA
recognizes the inexactitude of these
numbers.
///. Comments on Non-Carcinogens
A. Criteria for Chemical Classes
Issue 1
Comment summary: Two basic
approaches were taken in the
documents on chemical classes when
sufficient data were not available on all
members in a class:
(a] Criteria were derived for
individual chemicals on which sufficient
data were available and no criteria were
recommended for other chemicals in the
class.
(b) A criteria was derived for all or
some chemicals in the class based on
toxicity data on one or a few members
of the class.
Alternative "a" can be criticized for
"allowing" contamination .by "probably
hazardous compounds" (reasoning by
chemical analogy). Alternative "b" can
be criticized for applying a general
criteria to a specific compound for
which data are not available.
What guidelines with justifications
can be given for selecting either
alternative? What other alternatives
might be considered?
Response: The initial methodology did
not adequately address the problems
associated with deriving class criteria.
The following section has been added to
the methodology and serves as a useful
guide in the criteria derivation process.
A chemical class is broadly defined as
any group of compounds which are
considered in a single risk assessment
document In criteria derivation, isomers
ere regarded as a chemical class rather
than as a single compound. A class
criteria is an estimate of risk/safety
which applies to more than one member
of a class, and involves varying degrees
of extrapolation from available data on
some members of the class to other
class members on which sufficient data
are not available to derive a compound-
specific criteria (i.e., a criteria based on
data solely on the specific chemical for
which the criteria is derived).
A class criteria usually applies to
each member within the class rather
than to the sum of the compounds within
the class. While the potential hazards of
multiple toxicant exposure are not to be
minimized, a criteria, by definition, most
often applies to an individual
compound. Exceptions may be made of
complex mixtures which are produced,
released, and lexicologically tested as
mixtures (e.g., toxaphene and PCBs). For
such exceptions, some attempt should
be made to assess the effects of
environmental partitioning different
patterns of environmental transport and
degradation on the validity of the
criteria. If these effects cannot be
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assessed, an appropriate statement of
uncertainty should accompany the
criteria.
Because relatively minor structural
changes within a class of compounds
can have pronounced effects on their
biological activities, class criteria should
be avoided. Whenever sufficient
toxicologic data are available on a
chemical within a class, a compound
specific criteria for that chemical should
be developed. Nonetheless, for some
chemical classes, scientific judgment
may suggest a sufficient degree of
similarity among chemicals within a
class to justify a class criteria applicable
to some or all members within a class.
Such a judgment should be influenced
by a perceived risk to the human
population if a class criteria was not
derived.
The development of a class criteria
should take into consideration the
following:
(a) A detailed review of the chemical
and physical properties of chemicals
within the group should be available. A
close relationship within the class with
respect to chemical activity would
suggest a similar potential to reach
common biological sites within tissues.
Likewise, similar lipid solubilities would
suggest the possibility of comparable
absorption and tissue distribution.
(b) The amount of qualitative and
quantitative data for chemicals within
the group should be examined.
Obviously adequate toxicologies! data
on a number of compounds within a
group would provide a more reasonable
basis for extrapolation than minimal
data on one or two chemicals within a
group.
(c) Similarities In the nature of the
lexicological response to chemicals in
the class provides additional support for
the prediction that the response to other
members of the class may be similar. In
contrast, where the biological response
has been shown to differ markedly on a
qualitative and quantitative basis for
chemicals within a class, extrapolation
of a criteria to other members of that
class may not be appropriate.
(d) Additional support for the validity
of extrapolation of a criteria to other
members of a class could be provided
by evidence of similar metabolic and
pharmacokinetic data, if available, for
some members of the class.
Based on the above considerations, it
may be reasonable to divide a chemical
class into various subclasses. Such
divisions could be based on biological
endpoints (e.g.. carcinogens/non-
carcinogens), potency, and/or
sufficiency of data (e.g., a criteria for
some members of a class but no
criterion for others). While no a priori
limits can be placed on the extent of
subclasslfication. each must be
explicitly justified by the available data.
Class criteria, if properly derived and
supported, can constitute valid scientific
assessments of potential risk/safety and .
can be used in establishing appropriate
standards. Conversely, the development
of a class criteria from an insufficient
data base can lead to serious errors in
underestimating or overestimating risk/
safety and should be rigorously avoided.
Although scientific judgment has a
proper if not totally explicable role in
the development of class criteria, such
criteria will be useful and defensible
only if they are based on adequate data
and scientific reasoning rather than
intuition. The lack of data on
dissimilarity cannot be used as the basis
of a class criteria. Further, the definition
of sufficient data on similarities in
physical, chemical, pharmacokinetic, or
toxicologic properties to justify a class
criteria may vary remarkably depending
on the degree of superficial structural
similarity and the gravity of the
perceived risk. Consequently, it is
imperative that the criterion derivation
section of each document in which a
class criterion is recommended
explicitly address each of the key issues
discussed above and define, as clearly
as possible, the limitations of the
proposed criteria and the type of data
necessary to generate a compound-
specific criterion.
Class criteria should be corrected
when sufficient data become available
to derive a compound-specific criterion
that protects against the biological effect
of primary concern. The availability of a
good subchroni study would not result
necessarily in the abandonment of a
class criteria based upon potential
carcinogeniciry.
The Inability to derive a valid class
criteria does not and should not
preclude regulation of a compound or
group of compounds based upon
concern for potential human health
effects. The failure to recommend a
criterion is simply a statement that the
degree of concern cannot be quantified
from the available data and risk
assessment methodology.
Issue 2
Comment summary: To wrjat extent
can "guilt by association" be used to
derive a cancer-based'criteria for a
compound which has been tested for'
carcinogenic!ty with negative results
[e.g., bis(2-chloroisopropyl) ether in the
Chloroalkyl Ethers Ambient Water
Quality Criteria Document].
Response: As stated in the response to
Issue 1. "guilt by association" is only an
extremely limited role in criteria
derivation process.
B. Organoleptic Criteria .
Issue 3
Comment summary: Whenever
organoleptic criteria are derived,
corresponding toxicity based criteria
should be derived if possible.
Response: The Agency agrees. Since
organoleptic criteria are not based on
toxicologic information and have no
direct relationship to potential adverse
human health effects, both organoleptic
and toxicity based criteria are provided
whenever possible.
Issue 4
Comment summary: The quality of
organoleptic criteria should be assessed
in terms of experimental design and
statistical analysis. .
Response: The revised methodology
recognizes the limitations of most
organoleptic data:
With very few exceptions, the
publications which report taste and odor
thresholds are cryptic in their
descriptions of test methodologies,
number of subjects tested,
concentration/response relationships,
and sensory characteristics at specific
concentrations above the threshold.
Thus the quality of the data is usually
worse than the lexicological data used
for the setting of other criteria.
Consequently, a clear critical evaluator
of the available data on a compound's
organoleptic characteristics should
appear in the criteria document.
Issue 5
Comment summary: Criteria based on
organoleptic properties should not be
considered equal to criteria based on
toxicologic effects.
Response: The revised methodology.
makes a clear distinction between
organoleptic and toxicity based criteria.
The use of the criteria in the regulatory
process should reflect an appreciation of
this distinction.
C. Naturally Occurring Compounds
Issue 6
Comment summary: Background
levels should be defined in terms of the
quality of the data base and
geographical/seasonal variations.
Response: The documents summarize
data on background levels of naturally
occurring compounds and include
information on seasonal and/or
geographical variation when available.
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79371
Issue 7
Comment summary: A distinction
should be made between natural and
anthropogenic background.
Response: An attempt is made, with
extfeme difficulty, in the exposure
section of the documents to differentiate
between natural and anthropogenic
background. However, background
levels cannot be used directly to modify
the criteria. By definition, criteria should
not consider current levels of exposure
but are estimates of safe level or
incremental risk level exposures.
Background levels, both natural and
anthropogenic, should be considered if
the criteria are used to promulgate
standards.
Issues
Comment summary: What is the
minimum data base needed to define a
compound as essential?
Response: As indicated In the revised
methodology, elements will be accepted
as essential if the National Academy of
Sciences (NAS) Food and Nutrition
Board or a comparably qualified group
declares them as such. Elements not yet
determined to be essential, but for
which supportive data on "essentiality"
exists, were recommended to be
reviewed by a joint EPA/NAS
committee.
Issue 9 .
Comment summary: How can
essentiality be used to modify a criteria?
Response: The. following additions
have been made to the revised
methodology in response to this
question:
In order to be useful in modifying
toxicity/carcinogenicity based criteria,
essentiality must be quantified either as
a recommended daily allowance (RDAJ
or minimum daily requirement (MDR).
These levels must be compared to
estimated daily doses associated with
the adverse effect of primary concern.
The difference between the RDA or
MDR and the daily, doses causing a
specified risk level for carcinogens or
acceptable daily Intake (ADI) for non-
carcinogens defines the "window" of
daily doses from which the criteria
should be derived.
Because errors are inherent in
defining both essential and maximum
tolerable levels, the criteria should be
derived from dose levels near the center
of such a dose range. The decision to
use either the MDR or RDA will be
guided by the size of the window and
the quality of the essentiality and
toxicity estimates.
The modification of criteria by
consideration ofessentiality must
include all routes of exposure. If water
is a significant source of the MDR or
RDA, the criteria must allow for
attainment of essential intake.
Conversely, even when essentiality may
be attained from non-water sources,
standard criteria derivation methods
may be adjusted if the derived criterion
represents a small fraction of the ADI or
MDR. On a case-by-case basis, .the
modification in the use of the guidelines
may include the use of different safety
factors for non-carcinogens or other
modifications which can be explicitly
justified.
D.UseofNOAELs/NOELs
Issue 10
Comment summary: NOELs and
related effect terms should be defined
more clearly in the methodology.
Response: In the revised methodology,
the following additions have been made
to clarify the use of these terms:
In developing guidelines for deriving
criteria based on non-cardnogenic
responses, five types of response levels
are considered:
NOEL—No-Observed-Effect-Level
LOEL—Lowest-Observed-Effect-Level
NOAEL—No-Observed-Adverse-Eflect-Level
LOAEL—Lowest-Observed-Adverse-Effect-
Level
FEL—Frank-Effect-Level
In the above terms, adverse effects are
defined as any effect resulting in
functional impairment and/or
' pathological lesions that may affect the
performance of the whole organism, or
which contributes to a reduced ability to
respond to an additional challenge. The
word lowest refers to the incidence of
the effect in the tested population. It
should be noted that LOELs, NOAELs.
and LOAELs refer to exposure levels or
dosage zones which are experimentally
defined by upper and lower exposure
levels. NOELs and FELs, however, are
not defined at the lower and upper
exposure levels, respectively.
Issue 11 , ...-..' : ,.
Comment-summary: Considerations of
experimental design should be more
explicitly/quantitatively considered in
the criteria derivation process.
Response.-Tbe development of a rigid
system for considering experimental
design in criteria derivation would limit
the use of scientific judgment The ,
section of the methodology dealing with
the derivation of toxicity based criteria
has been extensively revised to allow
for the maximum use of scientific
judgment in selecting safety factors
based on both the quality of the
individual study and the weight of the
supporting scientific data.
E. Safety or Uncertainty Factors
Issue 12
Comment summary: Can the
guidelines for applying safety factors be
clarified or developed in greater detail
to minimize inconsistencies without
impairing scientific judgment?
Response: The following additions
have been included in the methodology
to allow for the use of greater judgment
in the application of safety factors,
while also requiring more, explicit
justification for the use of any
uncertainty, facton
The justifications for the various
safety factors can become very
restrictive if they are not employed with
care and judgment. This is the case
especially In those instances where the
data do not completely fulfill the
conditions for one category of
uncertainty factor and appear to be
intermediate between two categories.
Given the uncertainties in the entire ,
process, it is more appropriate to set the
operative uncertainty factor at some
intermediate-value on a logarithmic
scale (e.g., 32, being halfway between 10
and 100 on a logarithmic scale). If
intermediate values for uncertainty
factors are more representative of actual
conditions, then they are used.
In the selection of the uncertainty
factor approach, "no indication of
-carcinogenicity" is interpreted as the
absence of carcinogenic data from
animal studies or human epidemiology.
Short-term carcinogenicity screening
tests are considered in the criteria
documents, and are used in the .
derivation of numerical criteria and are
used to rule out the uncertainty factor
approach.
Because of the high degree of
judgment involved in the selection of a
safety factor, the criteria derivation
section of each document must provide
a detailed'discussion and justification
for both the selection of the safety factor
and the data for which it is applied. This
discussion should reflect a critical
review of the total data base. Factors to
be considered Include: number of ,.
animals tested, parameters tested,
species tested, quality of controls, dose
levels, route, dosing schedules, etc. An
effort should be made to differentiate
between coherent results which form a
lexicologically valid data base and data
which may be spurious in nature.
Issue 13
Comment summary: What, if any,
safety factor should be used when
deriving criteria from a threshold limit
value (TLV).
Response: The safety factor used
when deriving criteria from a TLV must
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79372
Federal Register / Vol. 45, No. 231 / Friday, November 28, 1980 / Notices
depend on the quality of the data base
on which the TLV is based,
considerations of uncertainties involved
in extrapolating data from inhalation to
oral exposures, and the quality of the
additional supporting data.
F. Related NOAEL, Issues
Issue 14
Comment summary: Can/should
concentration response curves
representing a "full range of effects" be
used in deriving criteria?
Response: No available system for
utilizing concentration response curves
in representing B full range of effects for
deriving criteria has been developed". If
such a system does become available, it
will be assessed by the Agency,
Issue IS
Comment summary: When more than
ODS method Is available to derive a non-
carcinogen criteria (e.g., 2-year chronic,
80-day, TLV), can guidelines be given for
selecting the most appropriate method?
Response: As Indicated in the revised
methodology, criteria can be based on
several different types of data (e,g,,
studies on humans or experimental
animals, subchronic or chronic exposure
periods, oral or Inhalation exposure
routes, TLVs or similar standards).
Specific guidelines for selecting a
particular study or approach have not
been recommended because of the many
Judgments] factors which are involved.
As indicated in the methodology,' the
criteria derivation section must
specifically state the reasons for
selecting the approach and study used
to derive the criteria.
Issue IB
Comment summary: The approach
used to derive criteria for non-
carcinogen^ Siay not adequately address
the ques;;, •• i of whether children are at
greater n*k tlmrj adults.
/ZespcM'.ierWhen specific data are
available on women or children as
groups at increased risk, it should be-
stated in the document and discussed in
the crileiia derivation section, but
should be used to modify the criteria
only if sufficient specific data are
available. This is a highly Judgmental
decision which must be made on an
individual case.
Issue 17
Comment summary: Criteria based on
carcinogenic effects might not be
adequate to protect humans from
mutagenic, teratogenic, or other toxic
effects.
Response: With very few exceptions,
criteria based on carcinogenicity are
probably protective for other toxic
effects. However, alternative criteria
can be derived based qn non-
carcinogenic effects on a case-by-case
basis if there is'any doubt of the level of
protection offered by the cancer based
criteria.
C. Alternative Approaches to the
Development of Criteria for Non-
Carcinogens
Issue 18
Comment summary: Is there a
reasonable way to use multiple NOEL/
NOAELs to derive criteria?
Response: The revised methodology
clearly Indicates that all toxicity must
be considered in deriving criteria and
multiple NOELS/NOAELs are used. A
detailed mathematical approach using
multiple NOEL/NOAEL data has not
been developed or accepted by the
scientific community.
Issue 19
Comment summary: Is there a
reasonable way to use dose/response
data to derive criteria?
Response: Mathematical models for
deriving non-cancer based criteria are
available. However, they have not
gained wide acceptance in human risk
assessment Until various models have
been reviewed in greater detail, the
Agency uses the current approach,
based on that recommended by the
National Academy of Sciences, as the
most appropriate,
Issue 20
Comment summary: Confidence
Intervals or a range should be used in
deriving criteria,
Response; A workable method for
using confidence intervals in deriving
non-cancer based criteria has not been
developed. Given the many
uncertainties involved in this process,
the use of confidence intervals could be
misleading in simply considering
problems in statistical variation without
considering problems in species to
species conversion. Safety factors are
an accepted procedure and are used to
consider both problems in statistical
variability as well as problems in
species to species conversions and
individual susceptibility.
H. Exposure
Issue 21
Comment summary: Should non-
cancer criteria be based on all sources
of exposure because they are derived
from estimates of ADIs (acceptable
daily intake) which define total daily
acceptable doses for man?
Response: The methodology has been
revised so that estimates of total
exposure can be considered in deriving
criteria. Estimates of water and fish
consumption arc used to derive the
criteria. However, the criteria levels can
be modified by considering all routes of
exposure in the standard-setting
process. This approach may be
particularly desirable because exposure
conditions will probably vary markedly
on a regional basis.
Issue 22
Comment Summary: If sufficient data
are not available on all sources of
exposure, can any reasonable
assumptions be made to factor in all
sources of exposure or can/should an
additional "uncertainty" factor be used?
Response: When no reasonable
estimate can be made of contributions
from non-fish diet and from air, it can be
assumed that one-half of the exposure
comes from water and fish and one-half
comes from other sources. This is
equivalent to using an additional safety
factor of 2. It is recognized that the
inability to quantify all sources of
exposure adds an additional element of
uncertainty to the criteria.
/, General Issues
Issue 23 .
Comment Summary: With the
exception of recommending "good
scientific judgment," can specific
guidelines be given for accepting or
rejecting a study or set of studies as a
data base for criteria derivation?
Response: Specific guidelines cannot
be given for accepting or refecting
studies. Scientific judgment must be
exercised in view of the magnitude of
the total evidence on the chemical or
chemicals under consideration. Chronic
data and appropriate exposure routes
are most desirable.
Issue 24
Comment Summary: Is there a need to
individualize the criteria derivation
process so that the "nature of the toxic
agent and its mechanism of action" can
be more explicitly considered? If so,
how can this be accomplished?
Response: The criteria derivation
process does consider as specifically as
possible the nature of the toxic agent
and, when known, the mechanism of
action.
Issue 25
Comment Summary: Is the Stokinger-
Woodward model adequate for
converting inhalation dose data to
"equivalent oral doses," or should a
more sophisticated approach be used?
Response: The derivation of water
quality criteria from inhalation data is
an admittedly tenuous process. The
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Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
79373
following guidelines have been added to
the methodology.
Estimating equivalencies of dose/
response relationships from one route of
exposure to another introduces an
additional uncertainty in the derivation
of criteria. Consequently, whenever
possible, ambient water quality criteria
should be based on data involving oral
exposures. Even with oral data.
differences in dosing schedules and
vehicles can be problematic. If oral data
are insufficient, data from other routes
of exposure may be used in deriving
water quality criteria. \
Inhalation data, including TLVs or
similar values, are the most common
alternative to oral data. Estimates of
equivalent doses can be made on the
basis of extensive pharmacokinetic data
for oral and inhalation routes, on the
basis of measurements of absorption
efficiency from ingested or inhaled
chemical, or on the basis of comparative
excretion data when the metabolic
pathways can be established to be
equivalent after oral or inhalation
dosing. When sufficient
pharmacokinetic data are available, the
use of accepted pharmacokinetic models
provides the most satisfactory approach
for dose conversions. However, if the
pharmacokinetic data are marginal or of
questionable quality, pharmacokinetic
modeling is inappropriate and may
result in an artifical sense of exactitude.
The Stoldnger and Woodward (1958)
approach, or similar models which are
based on assumptions of breathing rate
and absorption efficiency, can be used
as alternatives when data are not
sufficient to Justify pharmacokinetic
principles. Consequently, in using the
Stokinger and Woodward or related
models, the uncertainties inherent in
each of the assumptions and the basis of
each assumption should be clearly
stated in the derivation of the criteria.
The use of data involving other routes
of exposure to derive water quality
criteria should not be ruled out
However, as with Inhalation data, an
attempt should be made to use accepted
toxicologic and pharmacokinetic
principles to estimate equivalent oral
doses. If simplifying assumptions are
used, their bases and limitations must
be clearly specified.
Because of the uncertainties involved
in extrapolating from one route of
exposure to another and the consequent
limitations that this may place on the
derived criteria, the decision to disallow
such extrapolation and recommend no
criterion is highly judgmental and must
be made on a case-by-case basis. Such a
decision should balance the quantity
and quality of the available data against
a perceived risk to the human
population if no criteria is derived.
Issue 26
Comment Summary: Can/should
criteria be qualitatively or quantitatively
ranked in terms of their scientific
strength of validity? How could such a
ranking system be developed?
Response: The Agency is presently
assessing the quality of the data base
supporting individual criteria. This will
eventually result in the development of
a ranking system of all the priority
pollutants.
TV. Response to Public Comments on
Methodology to Derive Water Quality
Criteria
The Carcinogen Assessement Group
(CAG) and the Environmental Criteria
and Assessment Office-Cincinnati
(ECAO-Cln.) cf the U.S. Environmental
Protection Agency (EPA) has reviewed
in detail the public comments on EPA's
methodology to derive water quality
criteria for carcinogens. Since the
majority of the comments are concerned
with the low-dose extrapolation
procedure and since they are closely
related to each other, an appendix is
presented which summarizes our new
procedure to derive water quality
criteria and the rationale for selecting
the procedure and compares the new
with the old procedure. Much of the
criticism has been directed toward
utilization of the one-hit linear model for
estimation of the risk. After
considerable input by a peer review of
outside scientists, the multistage model
developed by Kenneth Crump has been
adopted in place of the one-hit model
extrapolation. The Appendix describes
the new multistage hit model Further
responses to the individual comments
are being presented below.
A. The One-Hit Model
Issue 1
Comment sununa/y.-.Several
comments criticize the one-hit model as
arbitrary, inappropriate, simplistic,
unrealistic. Inaccurate, not universally
accepted, and/or overly conservative.
Response: The Agency has adopted a
new procedure for deriving water
quality criteria which is conceptually
similar to, but operationally more
systematic than the one-hit procedure
used previously by the Agency.
Although the criteria calculated by the
new procedure are not appreciably
different than those calculated by the
old procedure as demonstrated in the
appendix, most of the general criticisms
do not apply to the new procedure.
Issue 2
Comment summary: Comments
pointed out that the EPA has declined to
use the one-hit model under the federal
pesticide laws for heptachlor and
chlordane.
Response: The commentor is correct
that the one-hit model was not used in
the chlordane-heptachlor suspension
hearings in 1375. However, in the
cancellation hearings, which were held
after the formation of the Carcinogen
Assessment Group and the adoption by
the Agency of the Interim Cancer
Assessment Guidelines and in the
proposed water quality criteria, one-hit
extrapolation model was used for risk
estimation. In the current final water
quality documents the "linearized"
multistage model is used; the
comparison between these two
approaches in the appendix to those
comments shows that the chlordane and
heptachlor data have the largest upward
curvature in the dose-response curve of
all the carcinogens in the water quality
list. For this reason the new approach
reduces the risk for chlordane and
heptachlor more than for the other
compounds. This example shows how
the new extrapolation procedure
compensates for the "overly
conservative" results of the one-hit
approach in cases where the dose-
response data is sharply concave
upward at low doses.
Issue 3
Comment summary: The EPA's choice
of this model because ". . . it gives
greater risk estimates than other
plausible models" (page 15978 of March
15, Federal Register] was criticized as
being a policy/political/social statement
rather than a scientific defense.
Response: See the appendix for
reasons for selecting linear, non-
threshold models.
Issue 4
Comment summary: The statement
that this model was endorsed by IRLG
(1979) was felt to have limited meaning
because this document has not yet been
reviewed and because the document is
merely a reiteration of policy.
Response: The model was not selected
on the endorsement of IRLG. See
appendix. •
Issue 5
Comment summary: In the
methodology (page 15978, column 1, first
full paragraph of the March 15. Federal
Register], this model is scientifically
defended as being consistent with three
basic concepts in chemical
carcinogenesis:
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Federal Register / Vol. 45. No. 231 / Friday, November 28, 1980 / Notices
a. The Linearity of the Doae-reaponae
Curve for Mutagens—This Is challenged
on the following points:
Hie shape of the dose response curve
In the low dose region cannot be
determined.
Not all assay systems give linear
dose-response patterns.
Some Ames tests are linear because
the liver microsomes are added in a
fixed amount and thus ". . . the laws of
first order kinetics require • linear
response to the variation in
concentration* of die test substance as
it la mediated by the activator,"
b. Chemicals which are Mutagens are
Likely to Induce Cancer—This is
challenged on the basis that not all
mutagens cause cancer. -
c. Epidemiology Studies on Radiation,
Cigarettes, and Aflatoxin show a Linear
Dose-response Pattern—This is
challenged on the following points:
Radiation carclnogeniclty cannot be
applied to chemical carcinogenicity
because they act by different
mechanisms.
Not aU radiation dose-response data
li linear.
Smoking data are compounded by
difficulties with cocarcinogens and other
exposures,
Aflatoxin data rely purely on
estimated exposures.
Response: [a] The commentor points
out that even in mutagenesis test
systems there is a level of mutagenic
response that is too small to be detected
and that below this level the shape of
the dose-response curve cannot be
measured. While this is true, the
Agency's point is that the mutagenesis
data available are fundamentally
consistent with a linear no-threshold
mechanism of action. Another
commentor has misinterpreted the
mutagenesis dose-response data. As
presented by the original authors, the
data show some residual mutagenic
activity at zero dose. This is interpreted
erroneously as being a threshold below
which no response occurs. Another
commentor supports the Agency's
contention that the mutagenesis dose-
response relationship is linear by giving
a possible explanation for the linearity.
(b) The fact that chemicals which are
mutagenic are "likely" to Induce cancers
does not imply that "all" mutagens
cause cancer. Furthermore, those
mutagens which were not shown
experimentally to be carcinogenic could
not be accepted unequivocally as non-
carcinogenic because of the uncertainty
in the study outcome.
(c) Both chemicals and radiation
cause DNA damage and subsequent
interference with the normal functioning
of DNA, although the mechanisms for
causing this damage are different for
radiation and chemicals.
Issue 0
Comment summary: Several
comments stated that the possibility of
thresholds for at least some chemical
carcinogens is not unreasonable, should
be addressed in greater detail and/or
cannot be resolved at this time. The
possibility of assuming a threshold was
recommended for the following
compounds; chloroform, PCBs,
acryionitrile, hexachlorocyclohexane,
chlorinated benzenes, and chlorinated
•thanes.
Response: Currently there is no
satisfactory method for estimating the
low-dose carcinogenic risk to
"epigenetic" chemicals. Until the
mechanisms for such action are
understood on a case-by-caso basis to
the pout of being able to justify a
specific extrapolation procedure, the
linear, no-threshold concept will be
assumed to be valid. The "linearized"
multistage approach now used result in
lower risks than the older "one-hit"
approach for compounds having a sharp
upward curvature.
For the specific chemicals referred to
in Issue 0, no evidence was presented in
support of a carcinogenic threshold dose
except for chloroform. Commentors
state that chloroform induces an
increased rate of cell proliferation,
which they implicitly equate with
carcinogenesis. at high doses because of
a cytotoxic response which la unrelated
to direct DNA Interaction and which
therefore is not expected to occur at low
doses. Three pieces of evidence are
cited in support of that position: (a)
chloroform Is not mutagenic in the Ames
tests: (b) at doses below IS mg/kg/day.
mice show no excess rate of DNA
synthesis in kidney and liver tissue. This
excess is expected for a cytotoxic
response leading to cell proliferation; (c)
Roe et al (1979) on the basis of
responses in four strains of mice, has
established a no-carcinogenic effect
level of 17 mg/kg/day, whereas the
positive NCI experiment used by EPA
for the water criterion was carried out at
200-400 mg/kg/day.
Before the existence of a threshold for
chloroform can be established several
issues need to be resolved: (a) are the
no-effect levels in the DNA synthesis
studies and in Roe's observations real
phenomena or only artifacts occurring
simply because the limit of detection in
these studies was being reached? (b)
The relation between the cellular
proliferation, which is alleged to be
manifested by increased DNA synthesis,
and carcinogenesis is unclear, since in
the mouse strains used by NCI kidney
tumors do not occur and liver tumors do
whereas in the experiments cited by a
commentor both liver and kidney exhibit
DNA synthesis.
Issue 7
Comment summary: A distinction
should be made between genetoxic and
epigenetic carcinogens based on
mutagenlcity data. These comments
imply that a threshold model would be
more appropriate for epigenetic
carcinogens,
Response. While it la true that moat
carcinogens do Interact with DNA, there
are some compounds, such as phorbol
esters in mouse skin studies and
phenobarbital in rat liver, which are
incomplete carcinogens by themselves;
but require another substance to initiate
or promote their action. In these studies
the effects are unrelated to DNA
interactions and apparently involve
important recovery processes. This
newly-developing field is not yet well
enough understood to justify the use of a
particular dose-response extrapolation
model.
Issue 8
Comment summary: Another group of
comments vigorously opposed the non-
threshold assumption used in the one-hit
model. Criticism of the non-threshold
assumption were most extensively
articulated by commenton which
contended that the non-threshold
assumption is:
Contrary to experience and logic, to
what is known of biological systems,
and to existing scientific data and is a
product of the desire to obtain a simple
and easy-to-use method for criteria
derivation.
A related comment contended that
thresholds are apparent for mutagens
and therefore—given the presumed
relationship of carcinogenicity to
mutageniclty—thresholds should be
postulated for carcinogens.
• Response: Commentors state that the
linear non-threshold model is: (a)
contrary to experience and logic; (b)
contrary to what la known about
biological systems; (c) contrary to
existing scientific data and (d) an
approach based on faith that could not
be disproved by any facts.
(a) The linear non-threshold model
does not imply, as suggested by a
commentor, either that (a) cancer is
inevitable In the general public or in
heavily exposed industrial workers or
that (b) all substances are carcinogenic.
ll simply states that the probability of a
person getting cancer is proportional to
the amount of carcinogen to which he is
exposed.
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Federal Register / Vol. 45. No. 231 / Friday, November 28. 1980 / Notices^
79375
: ' First order reaction processes are
iion In biological systems especially
,-riutagenesls.
(c) Dr. Blngham's article did not
ivoeate a elgmoid dose-response curve
preference to a linear curve, as stated
. the-commentor. She stated that
veral environmental factors can alter
e dose-response relationship, and
ould thereby change the curve
hichever way it was described. In fact,
T main point was that "until we
iderstand more about the primary
ircinogenle insult and its progression,
edicling or estimating thresholds is
iky," The Agency agrees with this
inclusion.
[d] The Agency agrees that it would
extremely difficult to use negative
idemiology data as proof that a
rcinogenic threshold exists for a
mpound having positive animal
suits. ,
iue 9
Comment summary:, Several
mments critlzed the one-hit model
cause it does not fit some
perimental data as well as other
idels. This was illustrated for
ptachlor, chlordane, and aflatoxin and
lorinated ethanes.
Response: The new extrapolation
slhod overcomes the difficulty In
ting the model to the data because the
iltistage model has enough flexibility
fit any montonically increasing dose-
jponse relationship. See also the
iponse to Issue 16.
uelO •
Comment summary: The application
the model was also criticized because
lisregards data at all but one dose
ei and fails to consider the results of
ler experiments.
Response: The new procedure does
t have these shortcomings. See
oendix.
ue 11
Comment summary: The highest
ency factor to the exclusion of all
er data should not be used in
icrating criteria because this process
:s not involve maximum-likely risk
imates. • . •-.
lesponse: In judging which of several
mal studies to use as the basis for the
mtitative risk estimate, the quality of
h study is considered as well as the
, nerical slope factor. As explained in
preamble, an experiment with a
all number of animals is rejected in
or of a larger experiment if the two
•e a similar dose-response
itionship. A similar rejection is also
-de if an experiment is judged to be
eliable for other reasons. Because of
the strain, species, and sex differences,
it is considered improper to calculate an
average response across all animal
species and designate this average as
the carcinogenic potency for animals in
general.
Issue 12
:Camment summary;". .., no"
experiment, however large and well run,
could ever reduce these estimates
{criteria)."
Response; In judging which of several
animal studies to use as the basis for the
quantitative risk estimate, the quality of
each study is considered as well as the
numerical slope factor. As explained in
the preamble, an experiment with a
small,number of animals ia rejected in
favor of a larger experiment if the two
have a similar dose-response
relationship. A similar rejection is also
made if an experiment is judged to be
unreliable for other reasons. Because of
the strain, species, and sex differences it
is considered improper to calculate an
average response across all animal
species and designate this average as
the carcinogenicity potency for animals
in general.
Issue 13
Comment summary: The EPA method
is insensitive to reproducibility of the
results, results at lower doses, and the
number of animals per dose group.
Response: In judging which of several
animal studies to use as the basis for the
quantitative risk estimate, the quality of
each study is considered as well as the
numerical slope factor. As explained in
the preamble, an experiment with a
small number of animals is rejected in
favor.of a larger experiment if the two
have a similar dose-response
relationship, A similar rejection is also
made if an experiment is judged to be
unreliable for other reasons. Because of
the strain, species, and sex differences,
it is considered improper to calculate an
average response across all animal
species and designate this average as
the carcinogenic potency for animals in
general.
Issue 14
Comment summary: Several examples
are given of the failure of the one-hit
model to predict cancer rates in humans
based on epidemlologic studies:
Analyses of data on; chloroform,
carbon tetra chloride,
tetracholoroethylene, aflatoxin,
chlordane, arsenic, and beryllium.
In a summary of analyses of DDT,
dieldrin, and aflatoxin, it is indicated
that the one-hit model predicts an
incidence of 153,000 liver cancers per
year but that the observed response rate
from all chemicals in only 3,000 to 4,000
per year. A similar analysis is made of
pollution exposure-cancer rates in the
Sacramento River area.
Response.' For chloroform, carbon.
tetrachloride, and tetrachloroethylene
the analysis assumed that all of the...
workers were exposed at the TLV levels
for their entire lifetime. In reality most
workers are not exposed continuously to
levels as high as the TLV and most work
for only a few years at these jobs. This
procedure overestimates the average
lifetime exposure by at least a factor of
10 and the risk estimates for the workers
are too high because of exposure
assumptions used by the commentor
rather than solely because of an
overestimated slope factor.
For aflatoxin the commentor showed
that the multistage model fits the
observed human data more closely than
the one-hit model. Therefore, that
analysis partially justifies the revised
procedure, although this compound is
not on the water quality list,
The criterion for arsenic was based on
human data, which was linear with
1 dose. However, none of the negative
epidemiology studies in areas with high
drinking water levels of arsenic was
inconsistent with the model developed
on the basis of the Taiwan skin cancer
data.
Commentors estimated that the
annual number of cancer cases caused
by beryllium intake is about 14,000.
They gave no reason why this number is
considered excessive considering that
400,000 cases per year are observed
from all causes.
Issue IS
Comment summary: Based on the
above types of analyses, several
comments recommended that
epidemlologic data be used to test and/
or modify risk estimates.
Response: The Agency agrees that
good epidemiological data should be
used to estimate or modify risk
estimates. The Agency always preferred
using epidemiological data to the animal
data in deriving water quality criteria.
Issue 16
Comment summary: Some comments
suggest that selection of a particular
model should be left open and subject to
the nature of the experimental data end
epidemiologic or metabolic information.
Response: The Agency does not agree
that the selection of a particular model
should be left open and subject to the
nature of the experimental data for the
following reasons. When behavior of the
dose-response curve at low doses is not
sufficiently understood, it is more
appropriate to predetermine the low-
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79376
Federal Register / Vol. 45. No. 231 / Friday. November 28. 1980 / Notices
dose extrapolation model. Considering
the fact that all the mathematically
analytic functions such as most of the
parametric dose-response curves could
be approximated by polynomials which
are dominated by the higher order terms
in the high-dose range, whereas they are
vanishingly small in the low-dose
regions it is not surprising to see that
different dose-response models could fit
well a set of high dose data while their
low-dose extrapolations differ
drastically. Therefore, the selection of
the extrapolation model should be based
on knowledge of carcinogenic
mechanisms (even though limited and
debatable) rather than being determined
solely by the high dose behavior of the
dose-response curve.
Issue 17
Comment summary: Other comments
suggested that the one-hit model should
be used only in the absence of data
suggesting that other models give a
better flt.
Response: See response to Issue 16
and the appendix.
Issue 18
Comment summary: Two comments
recommend that several models used for
analysis along with appropriate
confidence intervals would more
objectively reflect the state of scientific
knowledge.
Response: The inclusion of several
arbitrary models in order to get a range
of risk estimates would add no
additional scientific information while
at the same time would create confusion
and thereby undermine the utility of risk
estimates. The model chosen by the
Agency is regarded as giving a plausible
upper limit to the risk.
Issue li
Comment summary: A general
discussion of alternative models is given
in some of the comments. Specific
models recommended include: Logistic;
Probit; Multi-hit; Mantel and Bryan;
Weibull; and Pharmacokinetic.
Response: The Inclusion of several
arbitary models In order to get a range
of risk estimates would add no
additional scientific information while
at the same time would create confusion
and thereby undermine the utility of risk
estimates. The model chosen by the
Agency is regarded as giving a plausible
upper limit to the risk.
B. Use of Confidence Intervals
Issue 20
Comment summary: Confidence
intervals or a range should be used in
deriving criteria.
Response: The Agency feels that the
statistical confidence intervals should
not be used to express the range of
uncertainty of the criteria because this
range does not include major
uncertainties which are not quantifiable,
such as species differences in
metabolism, diet, target organ
specificity, and other biological
variables.
C. Species Conversion Factor (Wr
Issue 21
Comment summary: Comments
suggested that this factor may not be
appropriate for carcinogens because; (a)
DNA repair rates appear to be inversely
proportional to body weight, and (b)
mixed-function oxidase activity, which
may activate carcinogens, is higher in
rodents than in man. Examples were
given indicating that man is less
sensitive than experimental mammals to
chloroform, aflatoxln, and vinyl
chloride.
Response: Although some commentors
discussed reasons why the species
conversion factor, (70/W)V&, may not be
appropriate for particular compounds,
no suggestion was made for an
alternative method which would be
valid in general Commentors suggested
that mixed-function oxidase activity Is
lower in humans than in rodents and
that humans metabolize chloroform less
completely than animals, but facts like
these, even if quantified would have
uncertain implications to carcinogenic
potency in general because increased
metabolic activity could both enhance
carcinogenic potency by "inactivating"
the agent.
The fraction of a compound (e.g,
chloroform) unmetabolized may have no
relation at all to the amount of active
metablite formed. In the general method,
the cube root factor is Intended to
account only for the body size difference
between animal speciea as it relates to
the availability of the chemical to the
body tissues. Any specific knowledge
available on metabolism differences
would have to be incorporated as an
additional factor if it could be directly
related to cancer incidence. In general,
mixed-function oxidase activity has no
clear relation to cancer occurrence,
therefore, cannot be included in the
general approach.
The best apporach for checking the
validity of the species conversion factor
is to correlate carcinogenic potency of
agents in animals with that in humans
where suitable information is available.
This was done in a preliminary fashion
by Messelson [quoted by one
commentor) and is currently being
investigated by the Agency,
Issue 22 .
Comment summary: Data on
comparative metabolism should be used.
whenever possible, to modify the risk
estimate.
Response: See Issue 21 for response to
chloroform metabolism issue. The
Agency acknowledges that species
differences in metabolism should be
considered in all cases where the data
can be interpreted as being relevant to '
carcinogenicity. In the methodology
description the appropriate place to
incorporate this information is in the
factor r, called the absorption fraction.
D, Time-To-TumorData
Issue 23
Comment summary: Some comments
stated that the EPA's modification of the
one-hit model does not consider the
time-to-tumor concept
Response: The time-to-rumor concept
was incorporated in the one-hit
procedure by using the model P=l—exp
{—bd t*J where t is the average fraction
of a lifetime the tumor was observed
and is-a] so incorported into the current
approach. If sufficiently well defined
time-to-tumor data are available, a more
refined model would be used.
Issue 24
Comment summary: Other comments
contended that, because of the
relationship between dose and latency,
even potential carcinogens will not
induce tumors in a normal lifespan.
Examples were, given for beryllium and
arsenic.
Response: The arguments given in this
comment do not invalidate the criteria
which are associated with a lifetime risk
of 10~*. The arguments given in the
comment proceed as follows:
Let F[d,t) be the probability of cancer
by age t at exposure d. F is a monotonic
increasing function of both variables t
and d. Let d, be the exposure associated
with the lifetime risk of cancer 10~*
obtained by solving for d from the
equation F(d,t) • io~f and t = 70 which
is taken as the average lifespan. Based
on the arsenic risk assessment by the
CAG the comment argues that at
exposure d«= 0.002 fig/liter (where dc is
associated with a lifetime risk of 1CT6),
the median age would be 2,636 years
before cancer can occur, where 2,636 is
obtained by solving for I from the
equation F(d0,t) = 0,5.
Therefore, if the water concentration
is 0.002 tig/I the risk at 70 years is 10~*
and at 2,636 years it would be 0.5. These
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Federal Register / Vol. -45. No. 231 / Friday. November 28. 1980 / Notices
79377
are ~ it inconsistent statements, as
inv J by the commentor.
nent summary: One comment
sug, ^ted that studies in which t is less
than 0.75 may not be useful because of
insufficient time for tumor development.
Response: The t3 factor is necessary
when the carcinogenic response is so
strc -g that the animals die prematurely
of tunion. Hits Is true regardless of
whether the median time of death from
tumors Is greater or less than three-
fourths of their natural llfespan.
Issue 26
Comment summary: Another comment
raised questions about the experimental
difficulties of Druckery's work in
precisely determining time-to-tumor
development and the need to correct
tlme-to-tumpr data for the degree of
maUgnacy of the tumor.
Response:The tlme-to-tumor data is
used only when there was an early
terminal sacrifice. In this case the full
spectrum of tumor development is
observable histologically and the
difficulty of observing the precise time
of tumor development is not
encountered.
E. Mutagenicity Data
Issue 27
Comment summary: Mutagenicity
data should be given greater weight to
determine potential cardnogenidty
especially when mammalian bioassays
or epidemiology data are lacking.
R( -wise: See response to Issue 28.
Issue 28
Comment summary: The commentor
describes a method for using results
from short-term tests, such as the Ames
test or the hamster embryo in vitro
transformation test, to perform v
quantitative cardnogenidty risk
assessment
Response: The Agency does not
regard results from short term
mutagenidty tests, even those from a
test battery using several organisms,
equivalent to chronic whole animal
bioassays for cardnogenidty because of
the inherent differences between the
test systems utilized (i.e., bacteria and
cell cultures versus whole animals, in
which all the metabolic, distribution and
excretion systems of the body are
intact). Until correlations between the
carcinogenicity and mutagenidty of
agents become better understood and
more widely accepted, and until the
data base is more extensive, the Agency
is not justified in making quantitative
assessments of carcinogenicity based
solely on mutagenidty test results and
structure activity relationships. In *
decisions regarding the carcinogenicity
of agents, the Agency currently uses
short term bioassay tests only to support
equivocal findings of long term animal
bioassays and human studies.
F. Epidemiology Data
Issue 29
Comment summary. Epidemiology
data on societies other than the U.S.A.
should not be used because of
"dissimilar and possibly controlling
variables."
Response: The CAG feels that
epidemiological data on societies other
than the U.S.A. population can be used
as long as care Is taken in interpreting
and using the data.
Issue 30
Comment summary: Citing criteria for
arsenic and cadmium, the comment
states that: "Valid epidemiological
studies exploring a cause-and-'effect
relationship between exposure to a
substance and disease must avoid a
number of flaws: bias, confounding
factors, and the confusion of chance
associations with casual relationships.
The epidemiological studies used by the
Agency in criterion formulation fail to
avoid these flaws."
Response: While nearly every
epidemiologic study contains flaws in '
the sdentiflc sense, a regulatory agency
must interpret all data available, making
judgments as to whether the studies
were too flawed for proper conclusions.
In determining the carcinogenicity of a
substance, the Agency is sensitive to the
need to find human populations who
have been exposed to other agents also.
The appearance of rare types of cancers
and/or a dose-response trend, however.
often provlde(s) very positive evidence
of carcinogenidty. Such is the case with
the Taiwan drinking water survey. Here.
where artesian well water with a high
concentration of arsenic has been used
for more than 60 years, a high
correlation between amount of arsenic
and skin cancer was found In addition,
the pre-cancerous skin conditions were
pathonbmic of arsenic exposure, so that
there was little chance that the cancers
were caused by another agent.
Furthermore, the skin cancer is of a rare
form that was virtually unknown in
parts of Taiwan where the drinking
water arsenic content was small. In
addition, a positive association between
arsenic level in drinking water and the
prevalence of skin cancer has been
reported in at least three other areas in
the world.
Cadmium is an unusual situation in
that five independent populations
showed an excess of prostate cancer.
Even though each study is inconclusive
by itself for the reasons cited, a chance
occurrence of this finding is exceedingly
unlikely.
While the effect of many possible
confounding factors, especially
concomitant exposure to unknown
chemicals, cannot be accurately
determined, the Agency has the
responsibility of estimating criteria
levels with the best information
available.
C. Qualitative Determination of
Carcinogenicity
Issue 31
Comment summary: The commentor
states that: "A substance is currently
considered to be carcinogenic if it
produces a statistically significantly
higher than normal incidence of tumors
in treated animals in a single test. Such
a result is inconclusive, because of the
problems of false positives.
Response: In establishing a false
negative rate of P<0.05 the commentors
correctly point out that the false positive
rate is rather high. However, the careful
review of other information about the
compound reduces the effective false
positive rate.
Issue 32
Comment summary: The decision to
label a compound "a suspect human
carcinogen and therefore a potential
human carcinogen" based on
tumorigenicity in experimental
mammals has not been validated.
Several comments from the initial
publication of the methodology made a
similar critidsm.
Response: Among public health
authorities it is widely accepted that the
positive results in chronic animal
bioassays indicate that the agent poses
a potential risk for human
carcinogenicity. This attitude is
thoroughly summarized in the IRLG
report (Jour. Natl. Cancer Inst 63:241,
1979). In addition, a review by Tomatis
(Am. Rev. Pharmacol. Toxlcol. 79: 511,
1979) emphasized the value of rodent
bioassays in predicting human
carcinogenic risk.
Since 1976, (41FR 21402) the EPA has
been following the same regulatory
philosophy in evaluating carcinogenic
hazards. Therefore, contrary to the
comments, the EPA has not been acting
unilaterally without adequate public
notice.
Issue 33
Comment summary: The commentor
quotes a WHO publication: "It would be
unwise to classify a substance as a
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79370
Federal Register / Vol. 45. No. 231 / Friday. November 28, 1980 / Notices
carcinogen solely on the basis of a
species or strain-specific increased
incidence of tumors of a kind that occur
spontaneously with high frequency."
Response.- The CAG agrees partially
with the comment However, even if the
spontaneous Incidence is high, a
statistically significant enhancement of
the tumor incidence is of concern, and
other evidence for the compound should
be evaluated for consistency with that
finding.
Issue 34
Comment summary: Citing PAH as an
example, conunentors state that the
documents have been inconsistent in
qualitative determinations of
carcinogen! city.
Response: In cases such as PAH
where one criterion has to be set for an
entire class of compounds, the Agency
does not state that each chemical in the
class is a carcinogen, as Implied by the
commentor. Therefore, the PAH
example cited by the commentor does
not show that the Agency is Inconsistent
in classifying compounds as
carcinogenic.
The intended interpretation of the
criterion is that the risk is less than HT*
whenever the total concentration of all
PAH compounds in water is less then
the criterion. In a hypothetical case
where all of the PAH compounds In a
sample are non-carcinogenic, the
criterion would be too strict; however,
this situation seldom occurs. In most
cases where PAH is detected, a mixture
of compounds occurs and hi calculating
the criterion the assumption is made
that all components have the same
carcinogenic potency as benzdkt-
pyrene.
Isaue 35
Comment summary: Bis(2-
chloroisopropyljether (BCIE) yielded
negative results in an NCI bioassay.
Nonetheless, the cancer based criteria
based on an upper limit of the true
response rate was calculated because of
the structural similarity of BCIE to other
carcinogenic chloroalkyl ethers. The
commentor states that this is
inappropriate.
Response: As a response to the public
comments, the Agency has changed its
interpretation of data on bis(2-
ehlorolsopropyljether (BCIE). It Is no
longer considered to be carcinogenic
and, therefore, a criterion based on
carcinogenic data is not calculated.
Issue 36
Comment summary: Using the criteria
for chromium and asbestos as examples,
the commentors state that data on
inhalation carcinogenicity should not be
used to derive criteria if oral
carcinogenicity tests are negative.
Response: The criteria for chromium
(Cr) was derived on a marginally
significant digestive cancer Incidence
which occurred from inhalation
exposure (Enterline epidemiology
study). The digestive system cancer is
assumed to be caused by chromium (Cr)
which is removed from the respiratory
system by mucociliary action and then
swallowed. This is comparable to
exposure to chromium in drinking water.
Cr (VI) has not been adequately tested
.for its carcinogenic potential in animals;
therefore, further studies to assess the
caicinogenidty of Cr (VIJ by the oral
route would be desirable and necessary
before it is concluded that oral tests are
negative.
Asbestos has been shown to cause
peritonea] mesothelioma in humans and
is also associated with a significant
increase In human gastrointestinal
cancers. These are caused by inhaled
asbestos. Since up to 99 percent of the
inhaled asbestos is eventually
swallowed, the Agency feels that
asbestos-contaminated water could
cause the same type of gastrointestinal
cancers as inhaled asbestos.
H. Joint Action/Cocarcinogen/city
Issue 37
'Comment summary: The commentors
emphasized the potential importance of
cocarcinogenlcity and possible
synergisUc effects among carcinogens.
Response: The potential importance of
cocarcinogenicity and possible
synergistic effects among carcinogens
has not been addressed by the CAG hi
deriving water quality criteria, since
sufficient data is not available at this
time to make decisive judgments related
to these issues.
/. Site Specific vs. Total Tumors
Issue 38
Comment summary: No public
comments specifically addressed this '
issue. However, the methodology
committee should discuss the
appropriateness of using data on total
tumors for quantitative risk assessment
Response: Since chemicals generally
exert their carcinogenic effects at
specific organ sites, the incidence of
tumors at the responding sites is the
most relevant information to consider in
making either qualitative or quantitative
evaluations of hazard. The instances
where the tumor incidence at all sites
combined is elevated, but no one site or
group of sites is significantly increased,
are regarded as weak evidence of
carcinogenicity.
/. General Issues
Issue 39
Comment summary: Single unverified
bioassays should not be used for
establishing criteria for
dichlorobenzene.
Response: The comment does not
refer to carcinogenicity data since no
carcinogenic information was available
on dichlorobenzene.
Issue 40
Comment summary: Some comments
expressed concern with the types of
studies used to derive criteria. Another
comment implies that only data
published in referenced journals should
be used. Two commentors recommend
that explicit reasons be developed for
accepting or rejecting studies.
Response: The evaluations of
bioassay studies for carcinogenicity by
the CAG is sufficiently detailed to be
equivalent to that given in peer
reviewed journals.
Issue 41
Comment summary: The EPA "has
used animal studies without adequately
considering the nature of the toxic agent
and its mechanism of action, the
conditions of exposure, or the
physiological characteristics of the test
organism."
Response: The Agency routinely
considers all of the available
lexicological data cited by the
commentor and agrees that these factors
are important.
Issue 42
Comment summary: Several
comments questioned the
appropriateness of using studies from
one route of exposure—particularly
inhalation—to establish criteria for
ingestion.
Response: If a given chemical induced
a carcinogenic effect by inhalation at a
distant site, it is likely that the
compound could also produce a
carcinogenic effect by other routes of
administration. Therefore, the Agency
considers it appropriate to use
inhalation data to derive criteria for
ingestion, recognizing the difficulty of
determining the dose.
Issue 43
Comment summary: Treating all of the
proposed criteria as if they were based
upon equally valid data is not
scientifically sound: EPA must make
explicit the nature, extent, and quality of
the data utilized to estimate criteria.
Response: The Agency has indicated
which criteria should be regarded as
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Federal Register / Vol. 45. No. 231 / Friday. November 28.1980 / Notices
79379
marginal based on the nature of the
available data.
Issue 44
Comment summary: Criteria based on
carcinogenic effects might not be
adquate to protect humans from
mutagenic, teratogenlc, or other toxic
effects.
Response:^be U.S. EPA Office of
Health and Environmental Assessment
Is currently developing guidelines for
estimating the human risk to substances
producing mutagenic. teratogenlc, and
reproductive effects. \
Appendix
/. An Improved Procedure for Deriving Water
Quality Criteria
As discussed In the methodology document
(1981)* the Carcinogen Assessment Group
(GAG) has adopted a new prodedure which is
more systematic than the one-hit procedure
used previously by the GAG for calculating
the water quality criteria. The model selected
for the low dose extrapolation is given by
P(d}=l-exp[-(q.+q,d+ . . . +q,dk]]
At low doses, the upper confidence limit for
the extra risk
A(d) - P(d) -P(o)
1 -P(o)
has the form
Au(d) • l-«xp
That is, the risk A«(d) Is always linerarly
related to d at low doses. The constant qi*
corresponding to the 95 percent upper
confidence limit for A(dj is taken as the
carcinogenic potency for calculating the
water quality criteria.
Instead of extrapolating with the one-hit
model based on the lowest dose group
showing statistically slgniflcp.nl response as
previously used by the GAG. the new
procedure is employed because of the
following reasons: (1) the procedure Is more
systematic: (2) It invokes fewer arbitrary
assumptions; (3) the assumption of the low-
dose linearity Is not essential in the use of the
model and; (4) it incorporates data from all
of the dose groups which are consistent with
the multistage model At the same time, it is
conceptually consistent with the linear non-
threshold concept on which the one-hit
procedure was based.
The Agency recognizes that there Is no
really solid scientific basis for any
mathematical extrapolation model which •
relates carcinogen exposure to cancer risks at
the extremely low level of concentration that
must be dealt with tn evaluating the
environmental hazards. For practical reasons
such low levels of risk cannot be measured
directly either by animal experiments or by
epidemlologlc studies. We must therefor*,
depend on our current understanding of the
mechanisms of carcinogenesis for guidance
as to which risk model to use. At the present'
time the domlnat view of the carcinogenic
process Involves the concept that most agents
that cause cancer also cause Irreversible
damage to DNA. This position Is reflected by
the fact that a very large proportion of agents
that cause cancer are also mutagenic.
There is reason to expect the quanta! type
of biological response that is characteristic of
mutagenesis is associated with a linear non-
-.hold dose-response relationship. Indeed
:-;• is substantial evidence from
•: genesis studies with both ionizing
' Carcinogen Assessment Croup's Procedure for
Calculating Water Quality Criteria. Updated 1981.
radiation and a wide variety of chemicals
that this type of dose-response model is the
appropriate one to use. This Is particularly
true at the lower end of the dose-response
curve; al higher doses, there can be an
upward curvature probably reflecting non-
threshold dose-response relationships. The
linear non-threshold model is also consistent
with the relatively few epidemiologies!
studies of cancer responses to specific agents
that contain enough Information to make the
evaluation possible (e.g., radiation induced
leukemia, breast and thyroid cancer, and skin
cancer Induced by .arsenic In drinking water.
and liver cancer. Induced by aflatoxin in the
diet). There is also some evidence from
animal experiments that is consistent with
the linear non-threshold model (e.g., liver
tumors induced In mice by 2-
acetylaminofluorene in the large scale
EDmStudy at the National Center of
Toxlcological Research and the initiation
stage of the two-stage carcinogenesis model
in the rat liver and the mouse skin].
Because it has the best, albeit limited,
scientific basis of any of the current
mathematical extrapolation models, the
linear non-threshold model has been adopted
as the primary basis for risk extrapolation to
low levels of the dose-relationship. The risk
estimates made with this model should be
regarded as conservative, representing the
most plausible upper limit for risk. I.e.. the
true risk is not likely to be higher than the
estimate but it could be smaller.
//. Comparison of the new Procedure with the
Old (One-Hit) Procedure
The Agency had previously calculated the
slope b based on the one-hit model P=l-exp-
bd, using only the data from the lowest dose
group where the Incidence rate is statistically
significantly different from the control group
(see Federal Register. Part V. Thursday.
March 15.1979). The point estimate b was
taken as the carcinogenic potency for the
compound. Unlike the new procedure, the
upper confidence limit was not used because
the GAG recognized that the one-hit model is
usually conservative at low doses and thus
the point estimate b of the slope was
considered as an upper limit of the true
carcinogenic potency. This ad hoc approach'
"was used because it Is simple and easy to
understand.
Since b was considered an upper limit In
an ad hoc sense, it would be interesting to
compare the new procedure with the one-hit
procedure by calculating the ratio of two
carcinogenic potencies b/q/ for 21 chemical
compounds In the Proposed Water Quality
Criteria Documents which have data from at
least three dose groups. Except for chlordane
and heptachlor the new procedure agrees
with the one-hit procedure within a factor of
2. When the one-hit procedure is modified
(Table 1) the two procedures become
comparable. Therefore, the old procedure
could be used as a simple and quick way of
estimating the carcinogenic potency.
Table 1.—Ratio of Carcinogenic Potencies
Chemicals
b/q,'
CMortan
HeplacNor ..
Caibon tttfechlui no..
PAH
HCB—
1.2-OichlonMthane—
Acfytoflit/ito •*._.•>.-.««-
Henehkxoethane—
2.4.e-TncMoroeh
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