Design for the Environment Program
Alternatives Assessment Criteria for Hazard
Evaluation
Draft
January 2011
Office of Pollution Prevention & Toxics
U.S. Environmental Protection Agency
v^e£
U.S. EPA

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U.S. EPA Design for the Environment Program
Alternatives Assessment Criteria for Hazard Evaluation
Draft
January 2011
The criteria within this document will be applied during upcoming DfE
Alternatives Assessments. Lessons learned from the application of the
criteria during those assessments will be incorporated into a finalized
version.
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U.S. EPA Design for the Environment Program
Alternatives Assessment Criteria for Hazard Evaluation
Draft
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Table of Contents
1.	Introduction	-3-
2.	General Requirements	- 4 -
3.	Terms	- 5 -
4.	Toxicological Criteria	- 9 -
4.1.	Human Health Effects	- 9 -
4.1.1.	Acute Mammalian Toxicity	- 9 -
4.1.2.	Carcinogenicity	- 10 -
4.1.3.	Mutageni city / Genotoxi city	-11-
4.1.4.	Reproductive and Developmental Toxicity	- 12 -
4.1.5.	Neurotoxicity	- 13 -
4.1.6.	Repeated Dose Toxicity	- 14 -
4.1.7.	Sensitization	- 15 -
4.1.8.	Eye and Skin Irritation	- 16 -
4.1.9.	Endocrine Activity	-16-
4.2.	Environmental Toxicity and Fate	- 17 -
4.2.1.	Aquatic Toxicity	- 17 -
4.2.2.	Environmental Persistence	- 18 -
4.2.3.	Bioaccumulation	- 18 -
5.	Test Methods and Data Interpretation	- 20 -
5.1.	Acute Mammalian Toxicity	- 20 -
5.2.	Carcinogenicity	- 20 -
5.3.	Genetic Toxicity	-21-
5.4.	Neurotoxi city	- 22 -
5.5.	Repeated Dose Toxicity	- 22 -
5.6.	Reproductive and Developmental Toxicity	- 23 -
5.7.	Skin Sensitization	- 24 -
5.8.	Acute Aquati c Toxi city	- 24 -
5.9.	Persistence (measured as biodegradation)	- 25 -
5.10.	Bioaccumulation	- 27 -
6.	Appendix	-28-
Table A1. Alternatives Assessment Criteria Quick Reference	- 28 -
7.	References	-29-
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U.S. EPA Design for the Environment Program
Alternatives Assessment Criteria for Hazard Evaluation
Draft
January 2011
1. Introduction
The Design for the Environment (DfE) Program at the U.S. Environmental Protection Agency
developed the Alternatives Assessment Criteria for Hazard Evaluation as a transparent tool for
evaluating and differentiating among chemicals based on their concern for human health and
environmental hazard. The Criteria will be applied in upcoming DfE Alternatives Assessments
(for a current list of assessments to go: http://www.epa.gov/dfe/alternative assessments.html).
The Criteria could form the basis for decision-making by other organizations such as
manufacturers, retailers, other government agencies, and non-governmental organizations.
DfE Alternatives Assessments are multi-stakeholder partnerships that evaluate a chemical of
concern and its likely alternatives with the goal of "informing substitution" to safer alternatives.
The assessments are intended to reduce the likelihood of the unintended consequences that might
result if poorly understood alternatives were chosen. The Alternatives Assessment Criteria can
be used to place chemicals on a continuum of relative hazard to inform decision making.
The criteria are robust and comprehensive, including consideration for human health and
environmental hazards. For most endpoints, the criteria define "High," "Moderate," and "Low"
concern. Authoritative sources - the United Nation's Globally Harmonized System (GHS) for
the Classification and Labeling of Hazard Substances and U.S. EPA programs - are the basis for
these distinctions. In assigning a designation of Low, Moderate, or High concern for hazard, DfE
uses the best information available, both experimental and modeled.
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Alternatives Assessment Criteria for Hazard Evaluation
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2. General Requirements
2. 1 Data for all relevant routes of exposure will be evaluated.
2.2. The GHS criteria and data evaluation approach, and EPA risk assessment guidance
will be applied in the review of both no observed adverse effect
levels/concentrations (NOAEL/NOAEC) and lowest observed adverse effect
levels/concentrations (LOAEL/LOAEC). In general, NOAEL/NOAEC and
LOAEL/LOAEC values are preferred over no observed effect levels/concentrations
(NOEL/NOEC) and lowest observed effect levels/concentrations (LOEL/LOEC).
When available and appropriate, the results of benchmark dose modeling will also
be considered [1], In reviews that include conflicting data, a weight of evidence
evaluation will inform the hazard designation with a conservative approach aimed
at the protection of human health and the environment. All reviews will include an
assessment of potential impacts to vulnerable populations and life stages.
2.3	Use of existing data should follow the EPA HPV Challenge Program and OECD
HPV Programme data adequacy guidelines:
http://www.epa.gov/HPV/pubs/general/datadfin.htm.
2.4	When gathering data for evaluation under these criteria, a review of the open
literature including published peer-reviewed studies and government reports as well
as any confidential business information will be conducted.
2.5	Any known sensitivity of the test species or strain will be considered in the
evaluation of data against these criteria.

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Alternatives Assessment Criteria for Hazard Evaluation
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Terms
3.1.	Acute aquatic toxicity means the intrinsic property of a substance to be injurious to
an organism in a short-term, aquatic exposure to that substance [2],
3.2.	Acute mammalian toxicity refers to those adverse effects occurring following oral
or dermal administration of a single dose of a substance, or multiple doses given
within 24 hours, or an inhalation exposure of 4 hours [3],
3.3.	Attribute: The general property of the chemical that is being evaluated (e.g. acute
mammalian toxicity, persistence).
3.4.	The benchmark dose (or concentration) is the dose (or concentration) that is
associated with a specific measure or change of a biological effect. The calculation
of the benchmark dose (BMD) or concentration (BMC) generally represents the
central estimate of the dose or concentration associated with some level of response
above background. The lower limit of an on-side 95% confidence interval is
generally applied to the BMD and BMC [1],
3.5.	Bioaccumulation is a process in which a chemical substance is absorbed in an
organism by all routes of exposure as occurs in the natural environment, e.g.,
dietary and ambient environment sources. Bioaccumulation is the net result of
competing processes of chemical uptake into the organism at the respiratory surface
and from the diet and chemical elimination from the organism including respiratory
exchange, fecal egestion, metabolic biotransformation of the parent compound and
growth dilution [4],
3.6.	Biodegradation is a process in which the destruction of the chemical is
accomplished by the action of a living organism [5],
3.7.	Carcinogen denotes a chemical substance or mixture of chemical substances which
induces cancer or increases its incidence [6],
3.8.	A chemical is identified by its Chemical Abstract Service (CAS) number.
3.9.	Chronic aquatic toxicity means the intrinsic property of a substance to cause
adverse effects to aquatic organisms during aquatic exposures which are determined
in relation to the life-cycle of the organism [2],
3.10.	Criteria: Endpoints and cutoffs for attribute information. Example: oral acute
mammalian toxicity LD50 must be > 50 mg/kg. Data quality requirements
(including acceptable test methods and information sources) are developed for all
criteria.
3.11.	Dermal sensitizer: A substance that will lead an allergic response following skin
contact [7],
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3.12.	Developmental toxicity: Adverse effects in the developing organism that may
result from exposure prior to conception (either parent), during prenatal
development, or postnatally to the time of sexual maturation. Adverse
developmental effects may be detected at any point in the lifespan of the organism.
The major manifestations of developmental toxicity include: (1) death of the
developing organism, (2) structural abnormality, (3) altered growth, and (4)
functional deficiency [8],
3.13.	EC50: Half maximal effective concentration.
3.14.	Endocrine activity refers to a change in endocrine homeostasis caused by a
chemical or other stressor from human activities (e.g., application of pesticides, the
discharge of industrial chemicals to air, land, or water, or the use of synthetic
chemicals in consumer products.)
3.15.	An endocrine disruptor is an external agent that interferes in some way with the
role of natural hormones in the body. An agent might disrupt the endocrine system
by affecting any of the various stages of hormone production and activity, such as
by preventing the synthesis of hormones, by directly binding to hormone receptors,
or by interfering with the natural breakdown of hormones [9],
3.16.	Estimated concentration three (EC3): Estimated concentration of a test substance
needed to produce a stimulation index of three in the local lymph node assay, a test
used to evaluate dermal sensitization. [10]
3.17.	Genotoxicity: The more general terms genotoxic and genotoxicity apply to agents
or processes which alter the structure, information content, or segregation of DNA,
including those which cause DNA damage by interfering with normal replication
processes, or which in a non-physiological manner (temporarily) alter its
replication. Genotoxicity test results are usually taken as indicators for mutagenic
effects [11],
3.18.	An ingredient may be one chemical or a blend of multiple chemicals that are
intentionally added.
3.19.	LC50: Median lethal concentration.
3.20.	LD50: Median lethal dose.
3.21.	LOAEL: Lowest Observed Adverse Effect Level
3.22.	LOAEC: Lowest Observed Adverse Effect Concentration
3.23.	LOEC: Lowest Observed Effect Concentration
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3.24.	LOEL: Lowest Observed Effect Level.
3.25.	Mutagen: The term mutagenic and mutagen will be used for agents giving rise to
an increased occurrence of mutations in populations of cells and/or organisms [11],
3.26.	Neurotoxicity: An adverse change in the structure or function of the central and/or
peripheral nervous system following exposure to a chemical, physical, or biological
agent [12],
3.27.	NOAEL: No Observed Adverse Effect Level
3.28.	NOAEC: No Observed Adverse Effect Concentration
3.29.	NOEC: No Observed Effect Concentration
3.30.	NOEL: No Observed Effect Level
3.31.	Persistence: The length of time the chemical can exist in the environment before
being destroyed (i.e., transformed) by natural processes [13],
3.32.	Reproductive toxicity: The occurrence of biologically adverse effects on the
reproductive systems of females or males that may result from exposure to
environmental agents. The toxicity may be expressed as alterations to the female or
male reproductive organs, the related endocrine system, or pregnancy outcomes.
The manifestation of such toxicity may include, but not be limited to, adverse
effects on onset of puberty, gamete production and transport, reproductive cycle
normality, sexual behavior, fertility, gestation, parturition, lactation, developmental
toxicity, premature reproductive senescence, or modifications in other functions that
are dependent on the integrity of the reproductive systems [14],
3.33.	Respiratory sensitizer: A substance that will lead to hypersensitivity of the
airways following inhalation of the substance [7],
3.34.	Skin corrosion is the production of irreversible damage to the skin; namely, visible
necrosis through the epidermis and into the dermis, following the application of a
test substance for up to 4 hours [15],
3.35.	Skin irritation is the production of reversible damage to the skin following the
application of a test substance for up to 4 hours [15],
3.36.	Stimulation Index (SI): A value calculated to assess the skin sensitization potential
of a test substance that is the ratio of the proliferation in treated groups to that in the
concurrent vehicle control group. [10]
3.37.	Suitable analog: Suitable analogs will be based on a chemically (e.g., based on
chemical structure) or biologically (e.g., based on metabolic breakdown, or likely
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mechanistic/mode of action considerations) similar chemical. Guidance for
identifying a suitable analog can be found in OECD Series on Testing and
Assessment No. 80 Guidance on Grouping of Chemicals [16], The analog used
must be appropriate for the attribute being evaluated.
3.38. Weight-of-evidence: For the purposes of this document, weight-of-evidence refers
to the process of considering the strengths and weaknesses of various pieces of
information in reaching and supporting a conclusion concerning a property of the
substance [17],

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Alternatives Assessment Criteria for Hazard Evaluation
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4. Toxicological Criteria
Evaluation of chemicals under these criteria will be based on the best available data. In general,
DfE will use data in the following order of preference: 1) measured data on the chemical being
evaluated, 2) measured data from a suitable analog, and 3) estimated data from appropriate
models. EPA experts will evaluate the quality and reliability of both experimental and estimated
data. The majority of measured data are expected to be from laboratory experiments. However,
any available human data will be considered, e.g. Human Repeat Insult Patch Tests. In many
cases, the evaluation of human data will require a qualitative assessment, since the criteria are
primarily based on (non-human) animal studies. Human data may require appropriate review for
ethical treatment of the subjects.
In the absence of measured data on the chemical being evaluated, measured data from a suitable
analog and/or estimated data from computer models will be used. In the event that there are no
suitable analogs, that suitable analogs lack measured data, and the substance, or its analog cannot
be modeled, the hazard endpoint cannot be evaluated and will be designated "no data."
The links and references in this document are current as of the publication date of these Criteria.
EPA will use the most recent version of each authoritative list, EPA data interpretation guidance,
and test protocol when reviewing a chemical against these criteria. In the case where a GHS
reference in this document is superseded by a more recent version, EPA may choose to update
these Criteria to incorporate that newer version. EPA will consider all sources of developing
information, such as the EPA Endocrine Disruptor Screening Program [18] or enhancements to
estimation models such as EPI Suite™ [19] that occur over time. For convenience, a summary
of DfE's Alternatives Assessment Criteria is located in the Appendix (see Table Al).
4.1. Human Health Effects
4.1.1. Acute Mammalian Toxicity
DfE's acute mammalian toxicity criteria differentiate compounds based upon a common measure
of short term exposure toxicity, the median lethal dose or concentration (LD50 or LC50), through
oral, dermal, and respiratory routes. Chemical hazard designations will be made based upon the
criteria in Table 1. These values were derived from the GHS criteria [20],
Table 1. Acute Mammalian Toxicity Criteria for Hazard Designation
Acute Mammalian
Toxicity
Very
High
High
Moderate
Low
Oral LD50 (mg/kg)
<50
> 50 - 300
> 300 - 2000
>2000
Dermal LD50 (mg/kg)
<200
>200- 1000
> 1000-2000
>2000
Inhalation LC50
(vapor/gas) (mg/L)
Inhalation LC50
(dust/mist/fume) (mg/L/day)
<2
<0.5
>2-10
>0.5-1.0
>10-20
>1.0-5
>20
> 5
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4.1.2. Carcinogenicity
These criteria are designed to determine whether a compound is known, presumed, or suspected
to increase incidence of cancer, whether current data on carcinogenicity is equivocal, or whether
adequate studies have been conducted to show no increase in cancer incidents. Carcinogenicity
designations will be made according to the criteria in Table 2. Chemicals known, presumed, or
suspected to be carcinogenic to humans according to the authoritative lists in Table 3 will be
designated as High. When equivocal data or only positive structural alerts are present, a
designation of Moderate will be used. The basis for Low concern may include negative
carcinogenicity studies on the chemical being evaluated or negative studies on an analog and
lack of structural alerts, in addition to mechanistic considerations.
Table 2. Carcinogenicity Criteria for Hazard Designation
Carcinogenicity
High
Moderate
Low
Carcinogenicity
Positive results
Equivocal
results
Negative studies
and no structural
alerts
e 3. Criteria and Authoritative Lists Used to Designate Higl Hazard for Carcinogenicity
Authoritative Body
Classifications for High Hazard Designation
Globally Harmonized System
(GHS) [6]
Category 1A - Known to have carcinogenic potential for humans
Category 1B - Presumed to have carcinogenic potential for
humans
Category 2 - Suspected human carcinogens
National Toxicology Program
(NTP)
Known to be Human Carcinogen
Reasonably Anticipated to be Human Carcinogen
U.S. Environmental Protection
Agency (EPA)
(2005/1999) Carcinogenic to humans, Likely to be carcinogenic to
humans, or Suggestive evidence of carcinogenic potential
(1996) Known/Likely
(1986) Group A - Human Carcinogen, Group B - Probable
human carcinogen, or Group C - Possible human carcinogen
International Agency for
Research on Cancer (IARC)
Group 1 - carcinogenic to humans
Group 2A - probably carcinogenic to humans
Group 2B - possibly carcinogenic to humans
EU CMR List [21]
Category 1 - Known to be carcinogenic to humans
Category 2 - Should be regarded as if carcinogenic to humans
Category 3 - Cause for concern for humans owing to possible
carcinogenic effects
EU Risk Phrases [21]
R45: May cause cancer
R49: May cause cancer by inhalation
R40: Limited evidence of a carcinogenic effect
And all combination risk phrases containing one or more of the
above.
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4.1.3. Mutagenicity/Genotoxicity
The Mutagenicity/Genotoxicity criteria classify compounds based upon capacity to cause gene
mutations and/or chromosomal aberrations, whether current data are equivocal, or whether
adequate studies have been conducted that show lack of mutagenic potential.
Mutagenic/Genotoxic designations will be made according the criteria in Table 4. Those
compounds showing positive results and/or categorized by one of the authoritative bodies in
Table 5 will receive a High designation. When equivocal data or only positive structural data are
present, a designation of Moderate will be used. A Low hazard designation will be assigned for
chemicals with negative test data and no structural alerts.
Table 4. Mutagenicity/Genotoxicty Criteria for Hazard Designations
Mutagenicity/Genotoxicity
High
Moderate
Low
Mutagenicity/Genotoxicity
Positive results
Equivocal results
Negative for chromosomal
aberrations and gene
mutations, and no structural
alerts.
Table 5. Criteria and Authoritative Lists Used to Designate Higl Hazard for
Mutageni city / Genotoxi city	
Authoritative Body
Classifications for High Hazard Designation
Globally Harmonized System
(GHS) [11]
Category 1A - Chemicals known to induce heritable mutations in
germ cells of humans
Category 1B - Chemicals which should be regarded as if they induce
heritable mutations in the germ cells of humans
Category 2 - Chemicals which cause concern for humans owing to
the possibility that they may induce heritable mutations in the germ
cells of humans
EU CMR List [21]
Category 1 - Substances known to be mutagenic to humans
Category 2 - Substances which should be regarded as if they are
mutagenic to humans
Category 3 - Substances which cause concern for human owing to
possible mutagenic effects
EU Risk Phrases [21]
R46: May cause heritable genetic damage
R68: Possible risk of irreversible effects
And all combination risk phrases containing one or more of the above
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4.1.4. Reproductive and Developmental Toxicity
DfE's reproductive and developmental criteria classify compounds based upon the potential to
cause adverse effects on reproductive capacity and/or subsequent development of the offspring
through oral, dermal and respiratory exposure routes. In general, the NOAEL and LOAEL will
be considered as a basis for evaluation. Chemical hazard designations will be made based upon
the criteria in Table 6. These values were derived from the US EPA's Office of Pollution
Prevention & Toxics criteria for HPV chemical categorization [22],
Table 6. Reproductive and Developmental Toxicity Criteria for Hazard Designations	
Reproductive and
Developmental Toxicity
High Moderate Low
Oral (mg/kg/day)
Dermal (mg/kg/day)
Inhalation
(vapor/gas) (mg/L/day)
Inhalation
(dust/mist/fume) (mg/L/day)
< 1
< 50
< 0.1
< 100
50 - 250
0.1 - 0.5
100-500
1 -2.5
> 0.5
> 500
>2.5
>250
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4.1.5. Neurotoxicity
DfE's neurotoxicity criteria will classify compounds based upon observed neurotoxic effects
through oral, dermal, and respiratory exposure routes. Neurotoxic effects can be observed at
multiple levels of organization within the nervous system, including neurochemical, anatomical,
or behavioral, and across life stages. In general, NOAEL and LOAEL values will be considered
as the basis for evaluation. Chemical hazard designations will be made based on the criteria in
Table 7 which were derived from GHS criteria for Specific Target Organ Toxicity Repeated
Exposure [23],
The dose values in Table 7 are to be applied to 90-day repeated dose studies. Dose values are
tripled for chemicals evaluated in 28-day studies and similarly modified for studies of longer
durations.
Table 7. Neurotoxicity Criteria for Hazard Designations
Neurotoxicity
High
Moderate
Low
Oral (mg/kg-bw/day)
< 10
10-100
> 100
Dermal (mg/kg-bw/day)
<20
20 - 200
>200
Inhalation
< 0.2
0.2-1.0
>1.0
(vapor/gas) (mg/L/6h/day)
Inhalation
(dust/mist/fume) (mg/L/6h/day)
< 0.02
0.02-0.2
> 0.2
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4.1.6. Repeated Dose Toxicity
Chronic exposure will be evaluated with the results from repeated dose toxicity testing through
oral, dermal, and respiratory routes. In general, the NOAEL and LOAEL will be considered as a
basis for evaluation. Chemical hazard designations will be made based upon the criteria in Table
8 which were derived from the US EPA's Office of Pollution Prevention & Toxics criteria for
HPV chemical categorization [22],
The dose values in Table 8 are to be applied to 90-day repeated dose studies. Dose values are
tripled for chemicals evaluated in 28-day studies and similarly modified for studies of longer
durations.
Table 8. Repeated Dose Toxicity Criteria for Hazard Designations
Repeated Dose Toxicity
High
Moderate
Low
Oral (mg/kg-bw/day)
< 10
10-100
> 100
Dermal (mg/kg-bw/day)
<20
20 - 200
>200
Inhalation
(vapor/gas) (mg/L/6h/day)
Inhalation
(dust/mist/fume) (mg/L/6h/day)
<	0.2
<	0.02
0.2-1.0
0.02 - 0.2
>1.0
> 0.2
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4.1.7. Respiratory and Skin Sensitization
Evidence of whether repeated exposure to a chemical can induce an allergic response upon
contact will be evaluated in DfE's sensitization criteria. Both dermal and respiratory
sensitization will be considered. Chemical hazard designations will be made based upon the
criteria in Table 9 which were derived from the GHS guidance values [7], The GHS criteria for
categorizing chemicals as Category 1A or IB is given in Tables 10 and 11 respectively. For
Respiratory Sensitization, designations of High, Moderate, and Low will not be used. Instead, a
qualitative assessment of the available data will be prepared.
Table 9. Sensitization Criteria for Hazard Designations
Sensitization
High
Moderate
Low
Skin Sensitization
High frequency of
sensitization in humans
and/or high potency in
animals (GHS Cat. 1A)
Low to moderate
frequency of sensitization
in human and/or low to
moderate potency in
animals (GHS Cat. 1B)
Adequate data
available and
not GHS Cat.
1A or 1B
Respiratory Sensitization
For this endpoint, High/Moderate/Low etc. characterizations will not
apply. A qualitative assessment of the available data will be prepared.
Table 10. GHS Sensitization Criteria for High Hazard Designation
Assay
GHS Category 1A Criteria
Local lymph node assay
EC3 value < 2%
Guinea pig maximization
test
>	30% responding at < 0.1% intradermal induction dose or
>	60% responding at > 0.1% to < 1% intradermal induction dose
Buehler assay
>	15% responding at < 0.2% topical induction dose or
>	60% responding at > 0.2% to < 20% topical induction dose
Table 11. GHS Sensitization Criteria for	Hazard Designation
Assay
GHS Category 1B Criteria
Local lymph node assay
EC3 value > 2%
Guinea pig maximization
test
>	30% to < 60% responding at > 0.1% to < 1% intradermal induction dose or
>	30% responding at > 1% dermal induction dose
Buehler assay
>	15% to < 60%responding at > 0.2% to < 20% topical induction dose or
>	15% responding at > 20% topical induction dose
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4.1.8. Eye and Skin Irritation/Corrosivity
Data on a chemical's ability to cause eye and skin irritation/corrosivity will be reviewed under
these criteria. Hazard designations will be made based upon the criteria in Table 12. These
criteria were derived from the OPP Acute Toxicity Categories [24],
Table 12. Irritation Criteria for Hazard Designations
Irritation/Corrosivity
Very
High
High
Moderate
Low
Very
Low
Eye
Irritation/Corrosivity
Irritation
persists for
> 21 days
or corrosive
Clearing in
8-21 days,
severely
irritating
Clearing in 7
days or less,
moderately
irritating
Clearing in
less than
24 hrs,
mildly
irritating
Not
irritating
Skin
Irritation/Corrosivity
Corrosive
Severe
irritation at
72 hours
Moderate
irritation at 72
hours
Mild or
slight
irritation at
72 hours
Not
irritating
4.1.9. Endocrine Activity
EPA will evaluate endocrine activity rather than characterize hazard in terms of "endocrine
disruption". Evidence of a chemical having endocrine activity will be summarized in a narrative.
A) Data Resources
Endocrine activity can be defined as a change in endocrine homeostasis caused by a chemical
or other stressor from human activities (e.g., application of pesticides, the discharge of
industrial chemicals to air, land, or water, or the use of synthetic chemicals in consumer
products.). Data that will be considered include:
•	In vitro data such as hormone receptor binding assays or ex vivo assays
•	In vivo data from studies of intact animals or wildlife (including aquatic organisms)
•	Ethically conducted human studies
•	In vivo short term exposures or altered (e.g., ovariectomized) animal models
•	Structural similarity to known endocrine active substances using SAR tools such as AIM,
QSAR, etc.
•	Additional information gleaned from studies that are indicative of a chemical's endocrine
system interactions, such as changes in hormone profiles or reproductive organ weights.
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B) Criteria
Available data for each chemical will be evaluated for evidence of the presence of endocrine
activity.
•	If there are no data available to evaluate this endpoint, endocrine activity is unknown,
untested and would be marked with a "ND" indicating the absence of information. (No
Data)
•	If data show evidence of endocrine activity then the chemical will be designated as
potentially endocrine active, while noting caveats and limitations.
•	If data conclude no evidence of activity (no binding, perturbation, or evidence of
endocrine-related adverse effects) then the chemical will be designated as having no
evidence of endocrine activity, noting caveats and limitations.
In consultation with EPA toxicologists and risk assessors, DfE will provide a summary statement
of the available data, including the presence of equivocal or conflicting data and any limitations
to the available data. The level of confidence in the assessment will be noted.
4.2. Environmental Toxicity and Fate
4.2.1. Aquatic Toxicity
Chemicals will be assigned hazard designations based on either the LC50 or EC50 values for
acute aquatic toxicity, and lowest observed effect concentration (LOEC) for chronic aquatic
toxicity. The criteria used for making chemical hazard designations are shown in Table 13.
These values were derived from the EPA Office of Pollution Prevention and Toxics' (OPPT's)
New Chemicals Program [25] and OPPT's criteria for HPV chemical categorization [22],
Table 13. Aquatic Toxicity Criteria for Hazard Designations
Aquatic Toxicity
Very High
High
Moderate
Low
Acute Aquatic Toxicity
(LC50 or EC50) (mg/L)
<1.0
1 - 10
> 10-100
> 100
Chronic Aquatic
Toxicity
(LOEC) (mg/L)
< 0.1
0.1 - 1
>1-10
> 10
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4.2.2. Environmental Persistence
Persistence designations will be based on ultimate degradation. In the absence of data on
ultimate degradation, DfE will evaluate data on primary degradation of the compound and
consider the potential for degradation products of concern. Environmental monitoring data may
modify how a persistence designation is determined. If Ready Biodegradability test data are
available but the chemical did not pass, the chemical is evaluated based on measured data for
half-life.
In the absence of measured data on the substance of interest, DfE will evaluate data for suitable
analogs and estimated values from models such as EPI Suite or SPARC [26], Persistence
designations will be made based upon the criteria in Table 14. These values were derived from
OPPT's New Chemicals Program and the DfE Master Criteria, and reflect OPPT policy on PBTs
[27-29], For persistence in air, designations of High, Moderate, and Low will not be used.
Instead, a qualitative assessment of available data will be prepared.
Table 14. Criteria for Persistence Designations
Environmental
Persistence
Very
High
High
Moderate
Low
Very Low
Persistence in water,
soil or sediment
Half-life >
180 days
or
recalcitrant
Half life
of 60 -
180
days
Half-life < 60
but > 16 days
Half-life < 16
days OR
passes Ready
Biodegradability
test not
including the
10-day
window* No
degradation
products of
concern.
Passes Ready
Biodegradability
test with 10-day
window* No
degradation
products of
concern.
Persistence in air
For this endpoint, High/Moderate/Low etc. characterizations will not apply. A
qualitative assessment of available data will be prepared.
* See Ready Biodegradation test criteria [30-32],
4.2.3. Bioaccumulation
Data on the capacity for a compound to bioaccumulate will be evaluated. Environmental
monitoring data will be considered when available. The criteria used to make bioaccumulation
designations are shown in Table 15. These criteria were derived from OPPT's New Chemicals
Program [27], and Arnot & Gobas 2006 [4],
Table 15. Criteria for Bioaccumulation Designations
Bioaccumulation
Very High
High

Low
Bioaccumulation
(BAF / BCF)
> 100,000
100,000- 1,000
1,000- 100
< 100
Log BAF/BCF
>5
5-3
3-2
<2
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When experimental BAF or BCF data are available:
1)	If a measured log BAF or BCF is available and the value >2, apply the bioaccumulation
criteria in Table 15.
2)	If there are measured log BCF or log BAF values <2, consider application of the criteria on
a case-by-case basis. For example, if there is a single measured log BCF <2, use the upper
trophic BAF with metabolism from the BCFBAF model. If there are several measured
values which all support a designation of low bioaccumulation potential, then the chemical
will be designated as such.
When experimental BAF or BCF data are not available:
1)	If there are no measured BCF or BAF values, consider the octanol-water (Kow) and
octanol-air (Koa) partition coefficients. If a chemical has log Kow <2 and log Koa <5, it is
given a low designation for bioaccumulation [ref Gobas 2006]; an estimated BAF or BCF
is not needed. If no measured Kow and Koa values are available, they can be estimated
from the EPI Suite models KOWWIN and KOAWIN or other models that may be available
for these endpoints (e.g. SPARC).
2)	If bioaccumulation is not Low after evaluating log Kow and log Koa as defined above, and
there are no experimental bioaccumulation data, use estimated values (such as upper
trophic BAF with metabolism from EPI Suite's BCFBAF model) and apply the
bioaccumulation criteria in Table 15.
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5. Test Methods and Data Interpretation
This section lists examples of test methods used to develop data from which hazard designations
based upon the criteria in Section 4 will be made. In developing hazard designations we will
consider both peer-reviewed, published studies as well as unpublished data. Published, peer-
reviewed and guideline studies will be given the greatest weight.
5.1.	Acute Mammalian Toxicity - Test Methods
-	OPPTS Harmonized Guideline 870.1100: Acute oral toxicity [33]
-	OPPTS Harmonized Guideline 870.1200: Acute dermal toxicity [34]
-	OPPTS Harmonized Guideline 870.1300: Acute inhalation toxicity [35]
-	OECD Test Guideline 420: Acute Oral Toxicity-Fixed Dose Method [36]
-	OECD Test Guideline 423: Acute Oral Toxicity - Acute Toxic Class Method [37]
-	OECD Test Guideline 425: Acute Oral Toxicity - Up-and-Down Procedure [38]
-	OECD Test Guideline 402: Acute Dermal Toxicity [39]
-	OECD Test Guideline 403: Acute Inhalation Toxicity [40]
5.1.1. Sources for Data Interpretation
-	GHS Ch 3.1 Acute Toxicity [3]
-	EU Dangerous Substances Directive, http://ecb.irc.ec.europa.eu/documentation/.
To access the list of substances carrying Risk Phrases, click on
"CLASSIFICATION-LABELLING", then "DIRECTIVE 67-548-EEC", then
"ANNEX I OF DIRECTIVE 67-548-EEC", and then either of the files listed as:
"Annex I of Directive 67548EEC" [41]
5.2.	Carcinogenicity - Test Methods
-	OECD Test Guideline 451: Carcinogenicity Studies [42]
-	OECD Test Guideline 453: Combined Chronic Toxicity/Carcinogenicity Studies [43]
-	OPPTS Harmonized Guidelines 870.4200: Carcinogenicity [44]
-	OPPTS Harmonized Guidelines 870.4300: Combined chronic toxicity/carcinogenicity
[45]
-	NTP 2 Year Study Protocol: "Specifications for the conduct of studies to evaluate the
toxic and carcinogenic potential of chemical, biological and physical agents in
laboratory animals for the National Toxicology Program" [46]
Alternative Test Methods for Carcinogenicity
-	Modeled data from sources such as OncoLogic™ [47] are acceptable when data are
unavailable.
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5.2.1. Sources for Data Interpretation
-	EU Dangerous Preparations Directive Article 6 and Annex II (1999/45/EC and
subsequent updates/amendments) [48-50]
-	EU Dangerous Substances Directive, http://ecb.irc.ec.europa.eu/documentation/.
To access the list of substances carrying Risk Phrases, click on
"CLASSIFICATION-LABELLING", then "DIRECTIVE 67-548-EEC", then
"ANNEX I OF DIRECTIVE 67-548-EEC", and then either of the files listed as:
"Annex I of Directive 67548EEC" [41]
-	GHS Ch 3.6 Carcinogenicity [6]
-	Section 2, Hazard Assessment in Guidelines for Carcinogen Risk Assessment
http://oaspub.epa.gov/eims/eimscomm.eetfile7p download id=439797 [51]
-	Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to
Carcinogens, available at:
http://cfpub.epa.gov/ncea/CFM/recordisplav.cfm?deid=160003 [52]
5.3. Genetic Toxicity - Test Methods
Per GHS [11], results from multiple, acceptable test methods must be used in conjunction
for evaluation of genetic toxicity.
-	OECD Test Guideline 471 (OPPTS 870.5100): Bacterial Reverse Mutation Test [53,
54]
-	OECD Test Guideline 473 (OPPTS 870.5375): In vitro Mammalian Chromosome
Aberration Test [55, 56]
-	OECD Test Guideline 474 (OPPTS 870.5395): Mammalian Erythrocyte
Micronucleus Test [57, 58]
-	OECD Test Guideline 475 (OPPTS 870.5385): Mammalian Bone Marrow
Chromosome Aberration Test [59, 60]
-	OECD Test Guideline 476 (OPPTS 870.5300): In vitro Mammalian Cell Gene
Mutation Test [61, 62]
-	OECD Test Guideline 483 (OPPTS 870.5380): Mammalian Spermatogonial
Chromosome Aberration Test [63, 64]
-	OECD Test Guideline 486: Unscheduled DNA Synthesis (UDS) Test with
Mammalian Liver Cells in vivo [65], This guideline does NOT substitute in the
necessary minimum set for either the gene mutation or the chromosome aberration
test.
5.3.1. Sources for Data Interpretation
- EU Dangerous Substances Directive, http://ecb.irc.ec.europa.eu/documentation/.
To access the list of substances carrying Risk Phrases, click on
"CLASSIFICATION-LABELLING", then "DIRECTIVE 67-548-EEC", then
"ANNEX I OF DIRECTIVE 67-548-EEC", and then either of the files listed as:
"Annex I of Directive 67548EEC" [41]
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-	EU Dangerous Preparations Directive Article 6 and Annex II (1999/45/EC and
subsequent updates/amendments) [48-50]
-	GHS Ch 3.5 Germ Cell Mutagenicity [11]
5.4.	Neurotoxicity - Test Methods
-	OECD Test Guideline 424: Neurotoxicity Study in Rodents [66]
-	OPPTS Harmonized Guideline 870.6200: Neurotoxicity screening battery [67]
-	OECD Test Guideline 426: Developmental Neurotoxicity Study [68]
-	OPPTS Harmonized Guideline: 870.6300 Developmental neurotoxicity study [69]
5.4.1. Sources for Data Interpretation
-	Section 3, Hazard Characterization in Guidelines for Neurotoxicity Risk
Assessment [12]
-	GHS Ch. 3.9 Specific Target Organ Toxicity Repeated Exposure [23]
5.5.	Repeated Dose Toxicity - Test Methods
-	OECD Test Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents
[70]
-	OECD Test Guideline 409: Repeated Dose 90-Day Oral Toxicity Study in Non-
Rodents [71]
-	OECD Test Guideline 411: Subchronic Dermal Toxicity: 90-day Study [72]
-	OECD Test Guideline 413: Subchronic Inhalation Toxicity: 90-day Study [73]
-	OPPTS Harmonized Guideline 870.3100: 90-Day oral toxicity in rodents [74]
-	OPPTS Harmonized Guideline 870.3150: 90-Day oral toxicity in nonrodents [75]
-	OPPTS Harmonized Guideline 870.3250: 90-Day dermal toxicity [76]
-	OPPTS Harmonized Guideline 870.3465: 90-Day inhalation toxicity [77]
-	OECD Test Guideline 407: Repeated Dose 28-day Oral Toxicity Study in Rodents
[78]
-	OECD Test Guideline 410: Repeated Dose Dermal Toxicity: 28-day Study [79]
-	OECD Test Guideline 412: Repeated Dose Inhalation Toxicity: 28-day Study [80]
-	OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test [81]
-	OPPTS Harmonized Guideline 870.3050: Repeated dose 28-day oral toxicity study in
rodents [82]
-	OPPTS Harmonized Guideline 870.3200: 28-Day dermal toxicity [83]
5.5.1. Sources for Data Interpretation
-	GHS Ch 3.9 Specific Target Organ Toxicity Repeated Exposure [23]
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5.6. Reproductive and Developmental Toxicity - Test Methods
Fertility Test Methods
-	OECD Test Guideline 415: One-Generation Reproduction Toxicity Study [84]
-	OECD Test Guideline 416: Two-Generation Reproduction Toxicity Study [85]
-	OPPTS Harmonized Guideline 870.3800: Reproduction and fertility effects [86]
-	OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test
[87]
-	OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test [81]
-	OPPTS Harmonized Guideline 870.3550: Reproduction/developmental toxicity
screening test [88]
-	OPPTS Harmonized Guideline 870.3650: Combined repeated dose toxicity study
with the reproduction/developmental toxicity screening test [89]
Developmental Toxicity Test Methods
-	OECD Test Guideline 414: Prenatal Developmental Toxicity Study [90]
-	OPPTS Harmonized Guideline 870.3800: Reproduction and fertility effects [86]
-	OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test
[87]
-	OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test [81]
-	OPPTS Harmonized Guideline 870.3550: Reproduction/developmental toxicity
screening test [88]
-	OPPTS Harmonized Guideline 870.3650: Combined repeated dose toxicity study
with the reproduction/developmental toxicity screening test [89]
5.6.1. Sources for Data Interpretation
-	EU Dangerous Substances Directive, http://ecb.irc.ec.europa.eu/documentation/.
To access the list of substances carrying Risk Phrases, click on
"CLASSIFICATION-LABELLING", then "DIRECTIVE 67-548-EEC", then
"ANNEX I OF DIRECTIVE 67-548-EEC", and then either of the files listed as:
"Annex I of Directive 67548EEC" [41]
-	EU Dangerous Preparations Directive Article 6 and Annex II (1999/45/EC and
subsequent updates/amendments) [48-50]
-	GHS Ch 3.7 Reproductive Toxicity [91]
-	Part A, Section 3, Hazard Characterization in Guidelines for Reproductive
Toxicity Risk Assessment, http://www.epa.gov/ncea/raf/pdfs/repro51 .pdf [ 14]
-	Part A, Section 3, Hazard Characterization in Guidelines for Developmental
Toxicity Risk Assessment, http://www.epa.gov/NCEA/raf/pdfs/devtox.pdf [8]
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5.7.	Skin Sensitization - Test Methods
-	OECD Test Guideline 406: Skin Sensitization [92]
-	OECD Test Guideline 429: Skin Sensitization: Local Lymph Node Assay [10]
-	OPPTS Harmonized Guideline 870.2600: Skin Sensitization [93]
5.7.1. Sources for Data Interpretation
-	EU Dangerous Substances Directive, http://ecb.irc.ec.europa.eu/documentation/.
To access the list of substances carrying Risk Phrases, click on
"CLASSIFICATION-LABELLING", then "DIRECTIVE 67-548-EEC", then
"ANNEX I OF DIRECTIVE 67-548-EEC", and then either of the files listed as:
"Annex I of Directive 67548EEC" [41]
-	EU Dangerous Preparations Directive Article 6 and Annex II (1999/45/EC and
subsequent updates/amendments) [48-50]
-	GHS Ch 3.4 Respiratory and Skin Sensitization [7]
5.8.	Acute Aquatic Toxicity
Test Methods for Fish
-	OECD Test Guideline 203: Fish, Acute Toxicity Test [94]
-	OPPTS Harmonized Guideline 850.1075: Fish acute toxicity test, freshwater and
marine [95]
NOTE - EPA may request that the test be carried out using semi-static renewal or a flow-
through system with mean measured concentration. Any new testing should be done in
consultation with EPA.
Test Methods for Aquatic Invertebrates
-	OECD Test Guideline 202, Part 1, Daphnia sp., Acute Immobilisation Test [96]
-	OPPTS Harmonized Guideline 850.1010: Aquatic invertebrate acute toxicity test,
freshwater daphnids [97]
-	OPPTS Harmonized Guideline 850.1035: Mysid acute toxicity test[98]
NOTE - EPA may request that the test be carried out using semi-static renewal or a flow-
through system with mean measured concentration. Any new testing should be done in
consultation with EPA. A 96-hour Mysid shrimp acute toxicity test can be used in place
of a daphnid acute toxicity test when the latter is not available.
Test Methods for Algae
-	OECD Test Guideline 201, Alga, Growth Inhibition Test (and biomass) [99]
-	OPPTS Harmonized Guideline 850.5400: Algal toxicity, Tiers I and II (including
growth inhibition and biomass) [100]
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Alternative Test Methods, Acute Aquatic Toxicity
The following test methods may be considered, when relevant:
-	OPPTS Harmonized Guideline 850.1085: Fish acute toxicity mitigated by humic acid
[101]
-	OPPTS Harmonized Guideline 850.1025: Oyster acute toxicity test (shell deposition)
[102]
-	OPPTS Harmonized Guideline 850.1045: Penaeid acute toxicity test [103]
-	OPPTS Harmonized Guideline 850.1055: Bivalve acute toxicity test (embryo larval)
[104]
-	OPPTS Harmonized Guideline 850.4400: Aquatic plant toxicity test using Lemna
spp. Tiers I and II [105]
-	Modeled data from sources such as EPI Suite™ [19] are acceptable when data are
unavailable.
5.8.1. Sources for Data Interpretation
-	U.S. EPA Design for the Environment Program Master Criteria for Safer
Ingredients [28]
-	U. S. EPA EPI Suite™ [ 19]
5.9. Persistence
Data from experimental methods are generally preferred over estimations of persistence.
It is noted that simulation tests are likely to better describe the biodegradability of a
chemical in specific environmental conditions and may also contribute useful information
to the review. Environmental monitoring data may modify how a persistence designation
is determined.
Test Methods for Persistence
-	OECD Test Guideline 301: Ready Biodegradability (sections A-F) [30]
-	OECD Test Guideline 310: Ready Biodegradability - C02 in sealed vessels [31]
-	OPPTS Harmonized Guideline 835.3110: Ready biodegradability [106]
-	If the compound degrades by more than 40% in 28 days during one of the Ready
Biodegradability tests specified above or by more than 60% in one of the Inherent
Biodegradability tests detailed in OECD Test Guidelines 302 (A-C) [107-109], then
the half-life of a chemical is likely to be less than 60 days [110],
-	OECD Test Guideline 303A (OPPTS 835.3240): Aerobic Sewage Treatment:
Activated Sludge Units [111, 112]
-	OECD Test Guideline 309 (OPPTS Harmonized Guideline 835.3190): Aerobic
Mineralization in Surface Water - Simulation Biodegradation Test [113, 114]
-	OECD Test Guideline 314: Simulation Tests to Assess the Biodegradability of
Chemicals Discharged in Wastewater (Note: TG 314 uses elements of OECD TG
301, 303A, 309, 310, and 311) [115]
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-	OPPTS Harmonized Guideline 835.3280-Simulation Tests to Assess the Primary and
Ultimate Biodegradability of Chemicals Discharged to Wastewater [116]
-	OPPTS Harmonized Guideline 835.3170 - Shake Flask Die-Away Test [117]
-	OPPTS Harmonized Guideline 835.3180 - Sediment/Water Microcosm
Biodegradation Test [118]
Other Methods of Degradation
On a case-by-case basis, DfE will consider other routes of degradation in the
environment, such as hydrolysis or photolysis, and degradation in other relevant media,
for example, soil or sediment. In evaluating such degradation studies, DfE will consider
the relevance of that degradation pathway to the chemical in question as well as the
significance of the degradation.
5.9.1. Sources for Data Interpretation
-	U.S. EPA Design for the Environment Program Master Criteria for Safer
Ingredients [28]
-	U. S. EPA EPI Suite™ [ 19]
-	SPARC [26]
-	Revised Introduction to the OECD Guidelines for Testing of Chemicals, Section 3
[119]
-	OPPTS 835.0001 Principles and Strategies Related to Biodegradation Testing of
Organic Chemicals under the Toxic Substances Control Act (TSCA) [120]
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5.10. Bioaccumulation
A field-measured BAF (located in the literature) is the most preferred data for indicating
bioaccumulation. Environmental monitoring data will be considered when available.
Alternative Test Methods for Bioaccumulation
When a field-measured BAF is not available, the following test methods may be used:
-	OECD Test Guideline 305: Bioconcentration: Flow-through Fish Test [121]
-	OPPTS Harmonized Guideline 850.1710: Oyster BCF [122]
-	OPPTS Harmonized Guideline 850.1730: Fish BCF [123]
-	Modeled data from sources such as EPI Suite™ [19] are acceptable when data are
unavailable.
5.10.1. Sources for Data Interpretation
-	U.S. EPA Design for the Environment Program Master Criteria for Safer
Ingredients [28]
-	U. S. EPA EPI Suite™ [ 19]
-	SPARC [26]
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6. Appendix
Table Al. Alternatives Assessment Criteria Quick Reference
Human Health Effects
Acute Mammalian Toxicity
Very High
High
Moderate
Low

Oral LD50 (mg/kg)
£ 50
> 50 - 300
> 300 - 2000
>2000

Dermal LD50 (mg/kg)
£ 200
>200- 1000
> 1000-2000
>2000

Inhalation LC50
(vapor/gas) (mg L)
£ 2
>2-10
>10-20
>20

Inhalation LC50
(0.5-1.0
>1.0-5
>5

Carcinogenicity

High

Low



Positive results
Equivocal results
Negative studies and no
structural alerts

Mutagenicity/Genotoxicity

High

Low



Positive results
Equivocal results
Negative for chromosomal
abberations and gene mutations,
and no structural alerts.
Adequate data available.

Reproductive and
Developmental Toxicity

High

Low

Oral (mg/kg/day)

<50
50 - 250
>250

Dermal (nig/kg/day)

< 100
100-500
>500

Inhalation (vapoi, gas. mg/L/day)

< 1
1 -2.5
>2.5

Inhalation (dust, mist fume, mg/L/day)

<0.1
0.1-0.5
>0.5

Neurotoxicity

High
Moderate
Low

Oral (mg/kg-bw/day)

< 10
10-100
> 100

Dermal (mg/kg-bw/day)

<20
20 - 200
>200

Inhalation (vapor/gas) (mg L 6h day)

<0.2
0.2-1.0
>1.0

1 n h a 1 ati o n (d list, m istfn m e)
(mg/L/6h/day)

<0.02
0.02 - 0.2
>0.2

Repeated Dose Toxicity

High

Low

Oral (mg/kg-bw/day)

< 10
10-100
>100

D e rm a 1 (mg/kg -bw/d ay)

<20
20 - 200
>200

Inhalation (vapor gas) (mg/L/6h/day)

<0.2
0.2-1.0
> 1.0

Inhalation (dustmist'fume)
(mg/L/6h/day)

<0.02
0.02 - 0.2
>0.2

Sensitization

High

Low

Skin sensitization

High frequency of sensitization
in humans and/or high potency
in animals (GHS Cat. 1A)
Low to moderate frequency of
sensitization in human and/or
low to moderate potency in
animals (GHS Cat. 1B)
Adequate data available and not
GHS Cat. 1A or 1B

Respiratory Sensitization
For this endpoint, High/Moderate/Low etc. characterizations will not apply. A qualitative assessment of available data will be prepared.
Irritation/Corrosivity
Very High
High

Low
Very Low
Eye Irritation/Corrosivity
Irritation persists for > 21
days or corrosive
Clearing in 8-21 days, severely
irritating
Clearing in 7 days or less,
moderately irritating
Clearing in less than 24 hrs,
mildly irritating
Not irritating
Skin Irritation/Corrosivity
Corrosive
Severe irritation at 72 hours
Moderate irritation at 72 hours
Mild or slight irritation at 72
hours
Not irritating
Endocrine Activity
For this endpoint, High/Moderate/Low etc. characterizations will not apply. A qualitative assessment of available data will be prepared.
Environmental Toxicity and Fate
Aquatic Toxicity
Very High
High

Low

Acute Aquatic Toxicity
(LC50 or EC50) (mg L)
< 1.0
1 -10
> 10-100
> 100

Chronic Aquatic Toxicity
(LOEC) (mg/L)
<0.1
0.1 -1
>1-10
> 10

Environmental Persistence
Very High
High

Low
Very Low
Persistence in water, soil or sediment
Half-life > 180 days or
recalcitrant
Half life of60 - 180 days
Half-life <60 but £ 16 days
Half-life < 16 days OR passes
Ready Biodegradability test
not including the 10-day
window. No degradation
products of concern.
Passes Ready
Biodegradability test with
10-day window. No
degradation products of
concern.
Persistence in air (half-life days)
For this endpoint, High/Moderate/Low etc. characterizations will not apply. A qualitative assessment of available data will be prepared.
Bioaccumulation (BAF / BCF)
Very High
High

Low

!
> 100,000
100,000 -1,000
1,000-100
< 100

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7. References
1.	USEPA, Benchmark Dose Technical Guidance Document, External Review Draft.
EPA/630/R-00/001. 2000.
2.	GHS, Hazardous to the Aquatic Environment. 2009, United Nations.
3.	GHS, Acute Toxicity. 2009, United Nations.
4.	Arnot, J.A. and F.A. Gobas, A review of bioconcentrationfactor (BCF) and
bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms.
Environmental Reviews, 2006. 14: p. 257-297.
5.	Boethling, R.S. and D. Mackay, eds. Handbook of Property Estimation Methods for
Chemicals. 2000, CRC Press.
6.	GHS, Carcinogenicity. 2009, United Nations.
7.	GHS, Respiratory or Skin Sensitization. 2009, United Nations.
8.	USEPA, Guidelines for Developmental Toxicity Risk Assessment. Federal Register, 1991.
56(234): p. 63798-63826.
9.	USEPA, Special Report on Environmental Endocrine Disruption: An Effects Assessment
and Analysis. , in Risk Assessment Forum. 1997: Washington DC.
10.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 429: Skin Sensitization:
Local Lymph Node Assay. 2002.
11.	GHS, Germ Cell Mutagenicity. 2009, United Nations.
12.	USEPA, Guidelines for Neurotoxicity Risk Assessment. Federal Register, 1998. 63(93): p.
26926-26954.
13.	EPA. Persistent Bioaccumulative Toxic (PBT) Chemicals Final Rule 1999 [cited 2010
April 20]; Available from: http://www.epa.gov/fedrgstr/EPA-
WASTE/1999/October/Dav-29/f28169.htm.
14.	USEPA, Guidelines for Reproductive Toxicity Risk Assessment. Federal Register, 1996.
61(212): p. 56274-56322.
15.	GHS, Skin Corrosion/Irritation. 2009, United Nations.
16.	OECD, OECD Series on Testing and Assessment No 80.: Guidance on Grouping of
Chemicals. 2007.
17.	ECHA. Practical guide 2: How to report weight of evidence. 2010 [cited 2010 April
21]; Available from:
http://echa.europa.eu/doc/publications/practical guides/pg report weight of evidence.p
df.
18.	USEPA. Endocrine Disruptor Screening Program. October 21, 2009 [cited 2009
October 22, 2009]; Available from: http://www.epa.gov/endo/.
19.	USEPA, Estimations Programs Interface Suite ™. 2010, United States Environmnetal
Protection Agency: Washington, DC.
20.	Nations, U., Globally Harmonized System of Classification and Labeling of Chemicals. 3
ed. 2009.
21.	ECB, Annex I of Directive 67-548-EEC. 2007.
22.	USEPA, Methodology for Risk-Based Prioritization Under ChAMP. 2009, Office of
Pollution Prevention & Toxics.
23.	GHS, Specific Target Organ Systemic Toxicity Repeated Exposure. 2009, United Nations.
24.	USEPA. Label Review Manual. 2010 [cited 2010 September 27]; Available from:
http://www.epa.gov/oppfeadl/labeling/lrm/label-review-manual.pdf.
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25.	USEPA. Pollution Prevention (P2) Framework 2005 [cited 2010 September 27];
Available from: http://www.epa.gov/oppt/sf/pubs/p2frame-iune05a2.pdf.
26.	Hilal, S.H., S.W. Karickhoff, and L.A. Carreira, Prediction of Chemical Reactivity
Parameters and Physical Properties of Organic Compounds from Molecular Structure
Using SPARC, mEPA/600/R-03/030. 2003, U.S. Environmental Protection Agency:
Athens, GA.
27.	USEPA, Pollution Prevention (P2) Framework. 2005, Office of Pollution Prevention and
Toxics.
28.	USEPA, Design for the Environment Program Master Criteria for Safer Chemicals,
OPPT, Editor. 2010.
29.	USEPA, Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances
1999. p. 60194-60204.
30.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 301: Ready
Biodegradability. 1992.
31.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 310: Ready
Biodegradability - C02 in sealed vessels (Headspace Test) 2006.
32.	USEPA, Fate, Transport and Transformation Test Guidelines: OPPTS 835.3110: Ready
Biodegradability. 1998.
33.	USEPA, Health Effects Test Guidelines: OPPTS 870.1100: Acute Oral Toxicity. 1998.
34.	USEPA, Health Effects Test Guidelines: OPPTS 870.1200: Acute Dermal Toxicity. 1998.
35.	USEPA, Health Effects Test Guidelines: OPPTS 870.1300: Acute Inhalation Toxicity.
1998.
36.	OECD, OECD Guidelines for the Testing of Chemicals:
Toxicity - Fixed Dose Procedure. 2001.
37.	OECD, OECD Guidelines for the Testing of Chemicals:
-Acute Toxic Class Method. 2001.
38.	OECD, OECD Guidelines for the Testing of Chemicals:
Toxicity: Up-and-Down Procedure. 2006.
39.	OECD, OECD Guidelines for the Testing of Chemicals:
Toxicity. 1987.
40.	OECD, OECD Guidelines for the Testing of Chemicals:
Toxicity. 1981.
41.	ECB, Directive 67-548-EEC. 2007.
42.	OECD, OECD Guidelines for the Testing of Chemicals:
Studies. 1981.
43.	OECD, OECD Guidelines for the Testing of Chemicals:
Toxicity/Carcinogenicity Studies. 1981.
44.	USEPA, Health Effects Test Guidelines: OPPTS 870.4200: Carcinogenicity. 1998.
45.	USEPA, Health Effects Test Guidelines: OPPTS 870.4300: Combined Chronic
Toxicity/Carcinogenicity. 1998.
46.	NTP, Specifications for the conduct of studies to evaluate the toxic and carcinogenic
potential of chemical, biological and physical agents in laboratory animals for the
National Toxicology Program. 2006.
47.	Woo, Y.-t., et al., OncoLogic™, An Expert System for Prediction of the Carcinogenic
Potential of Chemicals. 2010, U.S. Environmnetal Protection Agency.
Test No. 420: Acute Oral
Test No. 423: Acute Oral toxicity
Test No. 425: Acute Oral
Test No. 402: Acute Dermal
Test No. 403: Acute Inhalation
Test No. 451: Carcinogenicity
Test No. 453: Combined Chronic
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48.	Council Directive 1999/45/EC, E. Commission, Editor. 1999: Official Journal of the
European Union.
49.	Council Directive 2001/60/EC, E. Commission, Editor. 2001: Official Journal of the
European Union.
50.	Council Directive 2006/8/EC, E. Commission, Editor. 2006: Official Journal of the
European Union.
51.	USEPA, Guidelines for Carcinogen Risk Assessment. USEPA Risk Assessment Forum,
2005.
52.	Barton, H., et al. Supplemental Guidance for Assessing Susceptibility from Early-Life
Exposure to Carcinogens 2005 [cited 2009 December 22, 2009]; Available from:
http://cfpub.epa.gov/ncea/CFM/recordisplav.cfm?deid=160003.
53.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 4 71: Bacterial Reverse
Mutation Test. 1997.
54.	USEPA, Health Effects Test Guidelines: OPPTS 870.5100: Bacterial Reverse Mutation
Test. 1998.
55.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 473: In Vitro
Mammalian Chromosome Aberration Test. 1997.
56.	USEPA, Health Effects Test Guidelines: OPPTS 870.5375: In Vitro Mammalian
Chromosome Aberration Test. 1998.
57.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 474: Mammalian
Erythrocyte Micronucleus Test. 1997.
58.	USEPA, Health Effects Test Guidelines: OPPTS 870.5395: Mammalian Erythrocyte
Micronucleus Test. 1998.
59.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 475: Mammalian Bone
Marrow Chromosome Aberration Test. 1997.
60.	USEPA, Health Effects Test Guidelines: OPPTS 870.5385: Mammalian Bone Marrow
Chromosome Aberration Test. 1998.
61.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 476: In Vitro
Mammalian Cell Gene Mutation Test. 1997.
62.	USEPA, Health Effects Test Guidelines: OPPTS 870.5300: In Vitro Mammalian Cell
Gene Mutation Test. 1998.
63.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 483: Mammalian
Spermatogonial Chromosome Aberration Test. 1997.
64.	USEPA, Health Effects Test Guidelines: OPPTS 870.5380: Mammalian Spermatogonial
Chromosome Aberration Test. 1998.
65.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 486: Unscheduled DNA
Synthesis (UDS) Test with Mammalian Liver Cells In Vivo. 1997.
66.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 424: Neurotoxicity
Study in Rodents. 1997.
67.	USEPA, Health Effects Test Guidelines: OPPTS 870.6200: Neurotoxicity Screening
Battery. 1998.
68.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 426: Developmental
Neurotoxicity Study. 2007.
69.	USEPA, Health Effects Test Guidelines: OPPTS 870.6300: Developmental Neurotoxicity
Study. 1998.
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70.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 408: Repeated Dose 90-
Day Oral Toxicity Study in Rodents. 1998.
71.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 409: Repeated Dose 90-
Day Oral Toxicity Study in Non-Rodents. 1998.
72.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 411: Subchronic
Dermal Toxicity: 90-day Study. 1981.
73.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 413: Subchronic
Inhalation Toxicity: 90-day Study. 1981.
74.	USEPA, Health Effects Test Guidelines: OPPTS 870.3100: 90-Day Oral Toxicity in
Rodents. 1998.
75.	USEPA, Health Effects Test Guidelines: OPPTS 870.3150: 90-Day Oral Toxicity in
Nonrodents. 1998.
76.	USEPA, Health Effects Test Guidelines: OPPTS 870.3250: 90-Day Dermal Toxicity.
1998.
77.	USEPA, Health Effects Test Guidelines: OPPTS 870.3465: 90-Day Inhalation Toxicity.
1998.
78.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 407: Repeated Dose 28-
day Oral Toxicity Study in Rodents. 1995.
79.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 410: Repeated Dose
Dermal Toxicity: 21/28-day Study. 1981.
80.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 412: Repeated Dose
Inhalation Toxicity: 28-day or 14-day Study. 1981.
81.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 422: Combined
Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening
Test. 1996.
82.	USEPA, Health Effects Test Guidelines: OPPTS 870.3050: Repeated Dose 28-day Oral
Toxicity Study in Rodents. . 2000.
83.	USEPA, Health Effects Test Guidelines: OPPTS 870.3200: 28-Day Dermal Toxicity.
1998.
84.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 415: One-Generation
Reproduction Toxicity Study. 1983.
85.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 416: Two-Generation
Reproduction Toxicity. 2001.
86.	USEPA, Health Effects Test Guidelines: OPPTS 870.3800: Reproduction and Fertility
Effects. 1998.
87.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 421:
Reproduction/Developmental Toxicity Screening Test. 1995.
88.	USEPA, Health Effects Test Guidelines: OPPTS 870.3550: Reproduction/Developmental
Toxicity Screening Test. 2000.
89.	USEPA, Health Effects Test Guidelines: OPPTS 870.3650: Combined Repeated Dose
Toxicity Study with the Reproduction/Developmental Toxicity Screening Test. 2000.
90.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 414: Prenatal
Development Toxicity Study. 2001.
91.	GHS, Reproductive Toxicity. 2009, United Nations.
92.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 406: Skin Sensitization.
1992.
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93.	USEPA, Health Effects Test Guidelines: OPPTS 870.2600: Skin Sensitization. 1998.
94.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 203: Fish, Acute
Toxicity Test. 1992.
95.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1075: Fish acute toxicity test,
freshwater and marine . . 1996.
96.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 202: Daphnia sp. Acute
Immobilisation Test. 2004.
97.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1010: Aquatic Invertebrate
Acute Toxicity Test, freshwater daphnids. . 1996.
98.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1035: Mysid acute toxicity test.
. 1996.
99.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 201: Alga, Growth
Inhibition Test. 2006.
100.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.5400: Algal toxicity, Tiers I and
II. . 1996.
101.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1085: Fish Acute Toxicity
Mitigated by Humic Acid. . 1996.
102.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1025: Oyster acute toxicity test
(shell deposition). . 1996.
103.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1045: Penaeid acute toxicity
test. . 1996.
104.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1055: Bivalve Acute Toxicity
Test (embryo larval). . 1996.
105.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.4400: Aquatic plant toxicity test
using Lemna spp. Tiers I and II. . 1996.
106.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.3110: Ready
Biodegradability. 1998.
107.	OECD. OECD Guidelines for the Testing of Chemicals: Test No. 302A: Inherent
Biodegradability: ModifiedSCAS Test. 1981; Available from:
http://lvsander.sourceoecd.org/vl=8284221/cl=38/nw=l/rpsv/ii/oecdiournals/16073 I0x/v
In3/s3/pl.
108.	OECD. OECD Guidelines for the Testing of Chemicals: Test No. 302C: Inherent
Biodegradability: ModifiedMITI Test (II). 1981; Available from:
http://oberon.sourceoecd.ore/vl=498282/cl=28/nw=l/rpsv/ii/oecdiournals/1607310x/vln
3/s5/pl.
109.	OECD. OECD Guidelines for the Testing of Chemicals: Test No. 302B: Inherent
Biodegradability: Zahn-Wellens/ EVP A Test. 1992; Available from:
http://lvsander.sourceoecd.org/vl=8284221/cl=38/nw=l/rpsv/ii/oecdiounials/16073 IQx/v
In3/s4/pl.
110.	Aronson, D., et al., Estimating biode gradation half-lives for use in chemical screening.
Chemosphere, 2006. 63(11): p. 1953-1960.
111.	OECD, OECD Guidelines for the Testing of Chemicals 303A: Aerobic Sewage
Treatment: Activated Sludge Units. 2001.
112.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.3240 Simulation
Test—Aerobic Sewage Treatment: A. Activated Sludge Units. 2008.
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113.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 309: Aerobic
Mineralisation in Surface Water - Simulation Biodegradation Test
2004.
114.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.3190 - Aerobic
Mineralization in Surface Water - Simulation Biodegradation Test. 2008.
115.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 314: Simulation Tests
to Assess the Biodegradability of Chemicals Discharged in Wastewater. 2008.
116.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.3280 Simulation
Tests to Assess the Primary and Ultimate Biodegradability of Chemicals Discharged to
Wastewater. 2008.
117.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.3170 - Shake Flask
Die-Away Test 1998.
118.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.3180 -
Sediment/Water Microcosm Biodegradation Test 1998.
119.	OECD, Revised Introduction to the OECD Guidelines for Testing of Chemicals, Section
3. Part 1: Principles and Strategies Related to the Testing of Degradation of Organic
Chemicals. 2006.
120.	USEPA, Fate, Transport and Transformation Test Guidelines: 835.0001 Principles and
Strategies Related to Biodegradation Testing of Organic Chemicals under the Toxic
Substances Control Act (TSCA). 2008.
121.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 305: Bioconcentration:
Flow-through Fish Test. 1996.
122.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1710: Oyster BCF. . 1996.
123.	USEPA, Ecological Effects Test Guidelines: OPPTS 850.1730: Fish BCF. . 1996.
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