U.S. EPA

DfE Screen for Solvents In Cleaning Products
1 Introduction

To identify safer solvents for use in cleaning products, Design for the Environment (DfE) focuses on the
characteristics (hazard endpoints) that are relevant to the types of solvents used in cleaners and that
distinguish safer solvents from those of greater concern. With cleaning solvents, in general, there are
potential concerns for the following endpoints: carcinogenicity, acute mammalian toxicity, reproductive
and developmental toxicity, repeated-dose toxicity, neurotoxicity, and environmental fate and toxicity.
These are termed the "Attributes of Concern." For the four classes of the Phase I Solvents (alcohols,
esters, ethylene glycol ethers, and propylene glycol ethers), the distinguishing hazard endpoints, which
are a subset of the Attributes of Concern, are: acute mammalian toxicity, reproductive and developmental
toxicity, repeated-dose toxicity, and environmental fate and toxicity. These are termed the "Distinguishing
Attributes of Concern."

DfE has selected the Distinguishing Attributes of Concern based on their ability to differentiate safer from
less safe solvents and on the availability or feasibility of generating data to address these endpoints. In
applying the screen, DfE will seek data on all Attributes of Concern; data on any single attribute that does
not meet DfE's threshold for a safer solvent will cause the solvent to fail the screen. For a solvent to pass
the screen, all available data must satisfy these thresholds and, very importantly, there must be data on
all distinguishing attributes—either on the chemical itself or a close analog—indicating that the solvent
meets safety thresholds. (Phase II Solvents—amides, amines, and terpenes—may have different
Distinguishing Attributes of Concern.)

Table 1 - DfE Screen for Solvents (Phase I)

Phase I Solvent Classes

Alcohols

Esters

Ethylene Glycol Ethers (EGEs)

Propylene Glycol Ethers (PGEs)

Attributes of Concern for Phase I
Solvents

Carcinogenicity

Neurotoxicity

Acute Mammalian Toxicity

Reproductive and Developmental Toxicity

Repeated-Dose Toxicity

Environmental Fate and Toxicity

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2 Terms

2.1	Alcohol: An organic compound containing at least one hydroxyl group (OH). Compounds having
two hydroxyl groups are referred to as "diols". Alcohols can be primary (1°), secondary (2°) or
tertiary (3°), depending on the position at which they are attached and the degree of branching of
the molecule.

2.2	Dust: Solid particles of a material suspended in a gas, usually air [1],

2.3	Esters: The condensation product of an alcohol with a carboxylic acid. Cyclic esters (lactones)
are not included in this definition and should not be reviewed using this screen because they are
generally unsuitable for use as solvents.

2.4	Ethylene glycol ethers (EGEs): Monoethers of mono- and di-ethylene glycol, and their
corresponding acetate esters; glyme and diglyme.

R-(OCH2CH2)nOH, and acetate esters
Me-(OCH2CH2)nOMe

Where R = branched or linear C1-C7 alkyl.

2.5	LOAEL: Lowest Observed Adverse Effect Level

2.6	Mist: Liquid droplets of a substance or mixture suspended in a gas, usually air [1],

2.7	NOAEL: No Observed Adverse Effect Level

2.8	Propylene glycol ethers (PGEs): This class includes mono- and di- ethers of 1,2-propanediol
(propylene glycol), 1-[2-hydroxy(methylethoxy)]-2-propanol (dipropylene glycol) and 1,2-bis[2-
hydroxy(methylethoxy)]propane (tripropylene glycol), and their corresponding acetate esters.

R-(OCH2CH2CH2)nOH, and acetate esters

Me-(OCH2CH2CH2)nOMe

Where R = branched or linear C1-C7 alkyl.

2.9	Vapor: The gaseous form of a substance or mixture released from its liquid or solid state [1],

3 Preferences

The following preferences and terms apply to all attributes and data requirements.

3.1	Every solvent must be screened individually. It is not expected that all solvents from these four
classes will pass the screen.

3.2	Data for all available routes of exposure will be evaluated. Failure to pass an endpoint by any
route of exposure results in failure to pass the screen.

3.3	Test data using dermal and inhalation exposure routes are preferred over oral exposure data
because the former are more likely routes of exposure for cleaning products.

3.4	The GHS criteria and data evaluation approach, and EPA risk assessment guidance, will inform
professional judgment in the review of both no observed adverse effect levels/concentrations
(NOAEL/NOAEC) and lowest observed adverse effect levels/concentrations (LOAEL/LOAEC).
NOAEL/NOAEC and LOAEL/LOAEC values are preferred to no observed effect

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levels/concentrations (NOEL/NOECs) and lowest observed effect levels/concentrations
(LOEL/LOECs).

3.5	The definitions in Section 2 shall apply in all cases.

3.6	Use of existing data should follow the EPA HPV Challenge Program's data adequacy
guidelines[2].

4 Attributes of Concern for all Solvents

Fully characterized endpoints for all chemicals are optimal. However, insufficient characterization may be
acceptable for the endpoints of carcinogenicity and neurotoxicity, because concern is not expected and
data are limited, respectively. Data or valid analogs will be reviewed whenever they are available, (see
Figure 1 below).

Does not Pass
Endpoint Criterion
and DfE Screen

Can be Considered
for DfE Screen

r



~v-~

Of

Presumptively

Insufficiently

Presumptively

Low Concern

Coneern

of Concern

characterized

of Low Concern

Solvents with test £

Structural

No testing

Structural

Solvents with

data

analogy1 to a

available and

analogy to a

test data

demonstrating

chemical of

lack of

chemical of

demonstrating

Concern

Concern

structural

Low Concern

Low Concern





analogy to a









tested chemical





1Can also include metabolic or mechanistic analogy.

Figure 1 - A diagrammatic representation of the continuum from high concern to low
concern and data requirements for screening qualification for carcinogenicity and
neurotoxicity.

4.1 CARCINOGENICITY

4.1.1	Criteria

Phase I Solvents will be screened for carcinogenicity based upon established lists and GHS criteria (see
Table 2).

4.1.2	Data Evaluation

Available data on the solvent or valid analog along with the OncoLogic™ [3] model will be used to assess
a solvent under GHS.

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Table 2 - Carcinogenicity

Authoritative Body

Criteria that will not pass the DfE Screen

International Agency for Research on
Cancer (IARC)

Group 1 - carcinogenic to humans
Group 2A - probably carcinogenic to humans
Group 2B - possibly carcinogenic to humans

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"

Globally Harmonized System (GHS)
[4]

Category 1 - Known or presumed human carcinogens1
Category 2 - Suspected human carcinogens1

'For chemicals where available carcinogenicity data have not been reviewed by IARC, NTP, or EPA

4.1.3	Preferred Test Methods

OECD Test Guideline 451: Carcinogenicity Studies [5];

OECD Test Guideline 453: Combined Chronic Toxicity/Carcinogenicity Studies [6];
OPPTS Harmonized Guideline 870.4200: Carcinogenicity [7];

OPPTS Harmonized Guideline 870.4300: Combined Chronic Toxicity/Carcinogenicity [8];
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" [9],

4.1.4	Data Interpretation

Section 2, Hazard Assessment in Guidelines for Carcinogen Risk Assessment [10]
GHS Ch 3.6 Carcinogenicity [4]

4.2 NEUROTOXICITY

4.2.1	Criteria

No solvents that are classifiable as neurotoxicants according to GHS [4] (see guidance values in Table 3)
will pass the screen for this endpoint. Insufficiently characterized solvents may be considered for the DfE
Screen.

4.2.2	Data Evaluation

Available data on the solvent or valid analog will be used to assess a solvent under GHS.

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Table 3 - Neurotoxicity

Route of Exposure

Guidance values1

Oral (mg/kg-bw/day)

> 100

Dermal (mg/kg-bw/day)

>200

Inhalation (gas) (ppm/6h/day)

>250

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

>1.0

Inhalation (dust/mist) (mg/L/6h/day)

>0.2

5The doses provided are for 90-day studies. Guidance values are tripled for chemicals evaluated in 28-day studies.

4.2.4	Preferred Test Methods

OECD Test Guideline 424: Neurotoxicity Study in Rodents [11] and
OPPTS Harmonized Guideline 870.6200: Neurotoxicity screening battery [12],

4.2.5	Optional Test Methods

Additional evidence from OECD Test Guideline 426: Developmental Neurotoxicity Study [13] and OPPTS
Harmonized Guideline: 870.6300 Developmental neurotoxicity study [14] can be used to screen solvents
for neurotoxicity.

4.2.6	Data Interpretation

Section 3, Hazard Characterization in Guidelines for Neurotoxicity Risk Assesssmeni [15]
GHS Ch. 3.9 Specific Target Organ Toxicity Repeated Exposure [16]

5 Distinguishing Attributes of Concern

Insufficient characterization is not acceptable for the endpoints listed below. Test data are acceptable and
data from analogous chemicals may be acceptable (see Figure 2.)

Does not Pass
Endpoint Criterion
and DfE Screen

Passes Endpoint Criterion
and Can Be Considered for
DfE Screen

Of
Cojipern

Solvents with

test data
demonstrating
Concern

Presumptively
of Concern

Structural
analogy1 to a
chemical of
Concern

"~~V"



Insufficiently
characterized
No testing
available and
lack of
structural
analogy to a
jsted chemical

Presumptively
of Low Concern

Structural
analogy to a
chemical of
Low Concern

Low Concern

Solvents with

test data
demonstrating
Low Concern

1Can also include metabolic or mechanistic analogy.

Figure 2 - A diagrammatic representation of the continuum from high concern to low
concern and data requirements for screening qualification for acute toxicity, PBT,
reproductive and developmental toxicity and repeated dose toxicity.

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5.1

ACUTE MAMMALIAN TOXICITY

5.1.1	Criteria

To be acceptable under the screen, Phase I Solvents must have a median lethal dose or concentration
greater than those values listed in Table 4.

5.1.2	Data Evaluation

Data must be available for at least one route of exposure. For inhalation, exposure must be at least four
hours; the thresholds for inhalation are the same for exposures greater than four hours. Exposures of less
than four hours will be evaluated on a case-by-case basis. Data for all available routes of exposure will be
evaluated. Failure to pass this endpoint by any route of exposure results in failure to pass the screen.

Table 4 Acute Mammalian Toxicity

Route of Exposure

Median Lethal
Dose/Concentration

Oral LD50 (mg/kg)

>2000

Dermal LD50 (mg/kg)

>2000

Inhalation LC50 (gas) (ppm)

>5000

Inhalation LC50 (vapor) (mg/L)

>20

Inhalation LC50 (dust/mist) (mg/L)

>5

5.1.3 Test Methods

OPPTS Harmonized Guideline: 870.1100 Acute oral toxicity [17];

OPPTS Harmonized Guideline: 870.1200 Acute dermal toxicity [18];

OPPTS Harmonized Guideline: 870.1300 Acute inhalation toxicity [19];

OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dose Method [20];

OECD Test Guideline 423: Acute Oral Toxicity - Acute Toxic Class Method [21];
OECD Test Guideline 425: Acute Oral Toxicity - Up-and-Down Procedure [22];
OECD Test Guideline 402: Acute Dermal Toxicity [23]; and
OECD Test Guideline 403: Acute Inhalation Toxicity [24],

5.2 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

5.2.1	Criteria

Phase I Solvents will not be acceptable under the screen if they are classifiable as reproductive toxicants
according to GHS [25] (see guidance values in Table 5). Following the SIDS Dossier [26], all solvents
must be reviewed for both fertility and developmental effects.

5.2.2	Data Evaluation

Data on reproductive and developmental toxicity must be available via at least one of the routes of
exposure below. Data for all available routes of exposure will be evaluated. Failure to pass this endpoint
by any route of exposure or toxicity effect (fertility or development) results in failure to pass the screen.

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Table 5 - Reproductive and Developmental Toxicity

Route of Exposure

Guidance Values

Oral (mg/kg-bw/day)

>250

Dermal (mg/kg-bw/day)

>200

Inhalation (gas)
(ppm/6h/day)

>250

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

>1.0

Inhalation (dust/mist)
(mg/L/6h/day)

>0.2

5.2.3 Test Methods

5.2.3.1	Fertility test methods, preferred

OECD Test Guideline 415: One-Generation Reproduction Toxicity Study [27] and
OECD Test Guideline 416: Two-Generation Reproduction Toxicity Study [28].

5.2.3.2	Fertility test methods, acceptable

OPPTS 870.3800: Reproduction and fertility effects [29]

The following test methods may be used to justify classification, per GHS [25]:

OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test [30]
OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test [31]

OPPTS Harmonized Guideline 870.3550: Reproduction/developmental toxicity screening
test [32]

OPPTS Harmonized Guideline 870.3650:Combined repeated dose toxicity study with the
reproduction/developmental toxicity screening test [33]

5.2.3.3	Developmental toxicity test methods, preferred

OECD Test Guideline 414: Prenatal Developmental Toxicity Study [34],

5.2.3.4	Developmental toxicity test methods, acceptable

OPPTS 870.3700: Prenatal developmental toxicity study [35]

The following test methods may be used to justify classification, per GHS [25]:

OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test [30]
OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test [31]

OPPTS Harmonized Guideline 870.3550: Reproduction/developmental toxicity screening
test [32]

OPPTS Harmonized Guideline 870.3650:Combined repeated dose toxicity study with the
reproduction/developmental toxicity screening test [33]

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5.2.4 Data Interpretation

Section 3, Hazard Characterization, Guidelines for Reproductive Toxicity Risk
Assessment [36]

Section 3, Hazard Characterization, Guidelines for Developmental Toxicity Risk
Assessment [37]

GHS Ch 3.7 Reproductive Toxicity [25]

5.3 REPEATED-DOSE TOXICITY
5.3.1 Criteria

Phase I Solvents will not be acceptable under the screen if they are classifiable as systemic toxicants
according to GHS [16] (see guidance values in Table 6).

Table 6 - Repeated-Dose Toxicity

Route of Exposure

Guidance values1

Oral (mg/kg-bw/day)

>100

Dermal (mg/kg-bw/day)

>200

Inhalation (gas) (ppm/6h/day)

>250

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

>1.0

Inhalation (dust/mist/fume) (mg/L/6h/day)

>0.2

7 The doses provided are for 90-day studies. Guidance values are tripled for chemicals evaluated
in 28-day studies and similarly modified for studies of longer durations.

5.3.2	Data Evaluation

Data must be available for at least one of the above routes of exposure, although inhalation and dermal
exposure data are preferred. Data for all available routes of exposure will be evaluated, and any study
must be 28 days or greater to satisfy this endpoint. Should testing be pursued to meet the screen data
requirement, a functional observational battery (FOB) should be added to the test method to provide
neurotoxicity information.

5.3.3	Preferred Test Methods

OECD Test Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents [38]
OECD Test Guideline 409: Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents
[39]

OECD Test Guideline 411: Subchronic Dermal Toxicity: 90-day Study [40]

OECD Test Guideline 413: Subchronic Inhalation Toxicity: 90-day Study [41]

OPPTS Harmonized Guideline 870.3100: 90-Day oral toxicity in rodents [42]

OPPTS Harmonized Guideline 870.3150: 90-Day oral toxicity in nonrodents [43]
OPPTS Harmonized Guideline 870.3250: 90-Day dermal toxicity [44]

OPPTS Harmonized Guideline 870.3465: 90-Day inhalation toxicity [45]

5.3.4 Acceptable Test Methods

OECD Test Guideline 412: Repeated Dose Inhalation Toxicity: 28-day Study [46]

OECD Test Guideline 410: Repeated Dose Dermal Toxicity: 28-day Study [47]

OECD Test Guidelines 407: Repeated Dose 28-day Oral Toxicity Study in Rodents [48]

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OECD Test Guideline 422, Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test [31]

OPPTS Harmonized Guideline 870.3050: Repeated dose 28-day oral toxicity study in
rodents [49]

OPPTS Harmonized Guideline 870.3200: 28-Day dermal toxicity [50]

5.3.5 Data Interpretation

GHS Specific Target Organ Toxicity - Repeated Exposure [16],

5.4 ENVIRONMENTAL TOXICITY AND FATE
5.4.1 Criteria

If a solvent is an acute aquatic toxicant, then it must biodegrade rapidly and not be bioaccumulative (see
Table 7, lines 1-3). If a solvent has low aquatic toxicity (Table 7, line 4), then its rate of biodegradation
may be >28 days as long as the half-life < 180 days and BCF < 5000.

Table 7 - Environmental Toxicity and Fate



Acute Aquatic Toxicity
Value (L/E/IC50)1'2

Persistence

(Measured in terms of rate of
biodegradation)

Bioaccumulation
Potential

1

If <1 ppm...

...then may be acceptable if the
component meets the 10-day window as
measured in a ready biodegradation
testc without degradation products of
concern01...

...and BCF <1000

2

If >1 ppm and <10 ppm...

...then the component must meet the
10-day window as measured in a ready
biodegradation test without degradation
products of concern01...

3

If >10 ppm and <100
ppm...

...then the component must meet the
28-day pass level as measured in a
ready biodegradation test without
degradation products of concern01...

4

If >100 ppm...

...then the component need not meet
the 28-day pass level as measured in a
ready biodegradation test if there are no
degradation products of concern01 and
half-life < 180 days...

s In general, there is a predictable relationship between acute aquatic toxicity and chronic aquatic toxicity for organic
chemicals, i.e., chemicals that have high acute aquatic toxicity also have high chronic aquatic toxicity. [51] Since acute
aquatic toxicity data are more readily available, the DfE Screens use these data to screen chemicals that may be toxic to
aquatic life. Where measured chronic toxicity data is available, it will be assessed with other data and applied in the screen
based on the relationship between acute and chronic aquatic toxicity.

bData, whether estimated or measured, are required for each of the following groups of organisms algae, aquatic
invertebrates and fish (all fresh water). Data for marine species may be added when available.

0 A case-by-case approach focusing on rate of biodegradation and degradation products of concern will be implemented for
solvents toxic to aquatic organisms at < 1ppm.

d Degradation products of concern are compounds with high acute aquatic toxicity (L/E/IC50 <10ppm) which mineralize <60% in 28
days.

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5.4.2 Preferred Test Methods, Persistence (measured as biodegradation)

OECD Test Guideline 301: Ready Biodegradability (sections A-F [52]);

OPPTS Harmonized Guideline 835.3110: Ready biodegradability [53]; and
Modeled data from sources such as EPISuite [54] and the PBT Profiler [55] are
acceptable when data are unavailable.

5.4.3	Preferred Test Methods, Bioaccumulation

A field-measured BAF (located in the literature) is the most preferred data for indicating bioaccumulation.
When not possible, the following test methods may be used:

OECD Test Guideline 305: Bioconcentration: Flow-through Fish Test [56];

OPPTS Harmonized Guideline 850.1710: Oyster BCF [57];

OPPTS Harmonized Guideline 850.1730: Fish BCF [58];

Modeled data from sources such as EPISuite [54] and the PBT Profiler [55] are

acceptable when data are unavailable. An estimated BAF is preferred to an estimated

BCF for compounds where log Kow > 5.

5.4.4	Preferred Test Methods, Acute Aquatic Toxicity

A baseline data set is required that should include freshwater test data for at least one species each of
algae, aquatic invertebrate and fish. Additional aquatic toxicity data in other species or in marine species
will also be reviewed if available.

5.4.4.1	Preferred test methods for fish

OECD Test Guideline 203: Fish, Acute Toxicity Test [59] and

OPPTS Harmonized Guideline 850.1075: Fish acute toxicity test, freshwater and marine
[60],

5.4.4.2	Preferred test methods for aquatic invertebrates

OECD Test Guideline 202, Part 1, Daphnia sp., Acute Immobilisation Test [61];

OPPTS Harmonized Guideline 850.1010: Aquatic invertebrate acute toxicity test,
freshwater daphnids [62]; and

OPPTS Harmonized Guideline 850.1035: Mysid acute toxicity test [63],

NOTE: A 96 hour Mysid shrimp acute toxicity test [70] can be used in place of a daphnid acute toxicity test when the
latter is not available.

5.4.4.3	Preferred test methods for aquatic plants

OECD Test Guideline 201, Alga, Growth Inhibition Test [64] and
OPPTS Harmonized Guideline 850.5400: Algal toxicity, Tiers I and II [65],

5.4.5	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 [66];
OPPTS Harmonized Guideline 850.1025: Oyster acute toxicity test (shell deposition) [67];
OPPTS Harmonized Guideline 850.1045: Penaeid acute toxicity test [68];

OPPTS Harmonized Guideline 850.1055: Bivalve acute toxicity test (embryo larval) [69];
OPPTS Harmonized Guideline 850.4400: Aquatic plant toxicity test using Lemna spp.
Tiers I and II [70]; and

Modeled data from sources such as ECOSAR [71] are acceptable when data are
unavailable.

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6

References

1.	GHS, Acute Toxicity. 2007, United Nations.

2.	USEPA. Determining the Adequacy of Existing Data. 1999 [cited; Available from:
http://www.epa.qov/HPV/pubs/qeneral/datadfin.htm.

3.	USEPA. OncoLogic™. 2008 [cited; Available from:
http://www.epa.oov/oppt/newchems/tools/oncolooic.htm.

4.	GHS, Carcinogenicity. 2007, United Nations.

5.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 451: Carcinogenicity
Studies. 1981.

6.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 453: Combined Chronic
Toxicity/Carcinogenicity Studies. 1981.

7.	USEPA, Health Effects Test Guidelines: OPPTS 870.4200: Carcinogenicity. 1998.

8.	USEPA, Health Effects Test Guidelines: OPPTS 870.4300: Combined Chronic
Toxicity/Carcinogenicity. 1998.

9.	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.

10.	USEPA, Guidelines for Carcinogen Risk Assessment. USEPA Risk Assessment Forum,
2005.

11.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 424: Neurotoxicity Study
in Rodents. 1997.

12.	USEPA, Health Effects Test Guidelines: OPPTS 870.6200: Neurotoxicity Screening
Battery. 1998.

13.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 426: Developmental
Neurotoxicity Study. 2007.

14.	USEPA, Health Effects Test Guidelines: OPPTS 870.6300: Developmental Neurotoxicity
Study. 1998.

15.	USEPA, Guidelines for Neurotoxicity Risk Assessment. Federal Register, 1998. 63(93):
p. 26926-26954.

16.	GHS, Specific Target Organ Systemic Toxicity Repeated Exposure. 2007, United
Nations.

17.	USEPA, Health Effects Test Guidelines: OPPTS 870.1100: Acute Oral Toxicity. 1998.

18.	USEPA, Health Effects Test Guidelines: OPPTS 870.1200: Acute Dermal Toxicity. 1998.

19.	USEPA, Health Effects Test Guidelines: OPPTS 870.1300: Acute Inhalation Toxicity.
1998.

20.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 420: Acute Oral Toxicity
- Fixed Dose Procedure. 2001.

21.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 423: Acute Oral toxicity -
Acute Toxic Class Method. 2001.

22.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 425: Acute Oral Toxicity:
Up-and-Down Procedure. 2006.

23.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 402: Acute Dermal
Toxicity. 1987.

24.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 403: Acute Inhalation
Toxicity. 1981.

25.	GHS, Reproductive Toxicity. 2007, United Nations.

26.	OECD, Manual for the Investigation ofHPV Chemicals, Annex 1 Guidance for completing
a SIDS Dossier 2007.

27.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 415: One-Generation
Reproduction Toxicity Study. 1983.

28.	OECD, OECD Guidelines for the Testing of Chemicals: Test No. 416: Two-Generation
Reproduction Toxicity. 2001.

29.	USEPA, Health Effects Test Guidelines: OPPTS 870.3800: Reproduction and Fertility
Effects. 1998.

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30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

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Reproduction/Developmental Toxicity Screening Test. 1995.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 422: Combined
Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening
Test. 1996.

USEPA, Health Effects Test Guidelines: OPPTS 870.3550: Reproduction/Developmental
Toxicity Screening Test. 2000.

USEPA, Health Effects Test Guidelines: OPPTS 870.3650: Combined Repeated Dose
Toxicity Study with the Reproduction/Developmental Toxicity Screening Test. 2000.
OECD, OECD Guidelines for the Testing of Chemicals: Test No. 414: Prenatal
Development Toxicity Study. 2001.

USEPA, Health Effects Test Guidelines: OPPTS 870.3700: Prenatal Developmental
Toxicity Study. 1998.

USEPA, Guidelines for Reproductive Toxicity Risk Assessment. Federal Register, 1996.
61(212): p. 56274-56322.

USEPA, Guidelines for Developmental Toxicity Risk Assessment. Federal Register,
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OECD, OECD Guidelines for the Testing of Chemicals: Test No. 408: Repeated Dose 90-
Day Oral Toxicity Study in Rodents. 1998.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 409: Repeated Dose 90-
Day Oral Toxicity Study in Non-Rodents. 1998.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 411: Subchronic Dermal
Toxicity: 90-day Study. 1981.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 413: Subchronic
Inhalation Toxicity: 90-day Study. 1981.

USEPA, Health Effects Test Guidelines: OPPTS 870.3100: 90-Day Oral Toxicity in
Rodents. 1998.

USEPA, Health Effects Test Guidelines: OPPTS 870.3150: 90-Day Oral Toxicity in
Nonrodents. 1998.

USEPA, Health Effects Test Guidelines: OPPTS 870.3250: 90-Day Dermal Toxicity.

1998.

USEPA, Health Effects Test Guidelines: OPPTS 870.3465: 90-Day Inhalation Toxicity.
1998.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 412: Repeated Dose
Inhalation Toxicity: 28-day or 14-day Study. 1981.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 410: Repeated Dose
Dermal Toxicity: 21/28-day Study. 1981.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 407: Repeated Dose 28-
day Oral Toxicity Study in Rodents. 1995.

USEPA, Health Effects Test Guidelines: OPPTS 870.3050: Repeated Dose 28-day Oral
Toxicity Study in Rodents. . 2000.

USEPA, Health Effects Test Guidelines: OPPTS 870.3200: 28-Day Dermal Toxicity.

1998.

Rand, G.M., ed. Fundamentals of Aquatic Toxicology. 2nd ed. 1995, Taylor & Francis:
Washington, DC.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 301: Ready
Biodegradability. 1992.

USEPA, Health Effects Test Guidelines: OPPTS 835.3110: Ready Biodegradability.

1998.

USEPA. EPI Suite ™. 2008 [cited June 2008]; Available from:
http://epa.gov/opptintr/exposure/pubs/episuite.htm.

SRC. PBTProfiler. 2006 [cited June 2008]; Available from: http://www.pbtprofiler.net/.
OECD, OECD Guidelines for the Testing of Chemicals: Test No. 305: Bioconcentration:
Flow-through Fish Test. 1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1710: Oyster BCF.	. 1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1730: Fish BCF. . 1996.

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63

64

65

66

67

68

69

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OECD, OECD Guidelines for the Testing of Chemicals: Test No. 203: Fish, Acute Toxicity
Test. 1992.

USEPA, Health Effects Test Guidelines: OPPTS 850.1075: Fish acute toxicity test,
freshwater and marine . .1996.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 202: Daphnia sp. Acute
Immobilisation Test. 2004.

USEPA, Health Effects Test Guidelines: OPPTS 850.1010: Aquatic Invertebrate Acute
Toxicity Test, freshwater daphnids. . 1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1035: Mysid acute toxicity test. .
1996.

OECD, OECD Guidelines for the Testing of Chemicals: Test No. 201: Alga, Growth
Inhibition Test. 2006.

USEPA, Health Effects Test Guidelines: OPPTS 850.5400: Algal toxicity, Tiers I and II. .
1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1085: Fish Acute Toxicity Mitigated
byHumicAcid. . 1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1025: Oyster acute toxicity test
(shell deposition). . 1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1045: Penaeid acute toxicity test. .
1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.1055: Bivalve Acute Toxicity Test
(embryo larval). . 1996.

USEPA, Health Effects Test Guidelines: OPPTS 850.4400: Aquatic plant toxicity test
using Lemna spp. Tiers I and II. . 1996.

USEPA. ECOSAR. 2000 [cited; Available from:
http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

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