Screening-Level Hazard Characterization Pyridine and Pyridine Derivatives Category SUB-CATEGORY I Pyridine (CASRN 110-86-1) 2-Picoline (CASRN 109-06-8) 3-Picoline (CASRN 108-99-6) 4-Picoline (CASRN 108-89-4) Pyridine, alkyl derivatives (CASRN 68391-11-7) SUB-CATEGORY II Nicotinonitrile (CASRN 100-54-9) Picolinonitrile (CASRN 100-70-9) SUB-CATEGORY III Piperidine (CASRN 110-89-4)

U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

SCREENING-LEVEL HAZARD CHARACTERIZATION
Pyridine and Pyridine Derivatives Category

SUB-CATEGORY I
Pyridine (CASRN 110-86-1)

2-Picoline (CASRN 109-06-8)

3-Picoline (CASRN 108-99-6)

4-Picoline (CASRN 108-89-4)

Pyridine, alkyl derivatives (CASRN 68391-11-7)

SUB-CATEGORY II
Nicotinonitrile (CASRN 100-54-9)

Picolinonitrile (CASRN 100-70-9)

SUB-CATEGORY III

Piperidine (CASRN 110-89-4)

The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary
initiative aimed at developing and making publicly available screening-level health and
environmental effects information on chemicals manufactured in or imported into the United
States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship
entailed the identification and initial assessment of the adequacy of existing toxicity
data/information, conducting new testing if adequate data did not exist, and making both new
and existing data and information available to the public. Each complete data submission
contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the
environment.

The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is
evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored
chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions.

They are not intended to be definitive statements regarding the possibility of unreasonable risk of

1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.

2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

injury to health or the environment.

The evaluation is performed according to established EPA guidance2'3 and is based primarily on
hazard data provided by sponsors; however, in preparing the hazard characterization, EPA
considered its own comments and public comments on the original submission as well as the
sponsor's responses to comments and revisions made to the submission. In order to determine
whether any new hazard information was developed since the time of the HPV submission, a
search of the following databases was made from one year prior to the date of the HPV
Challenge submission to the present: (ChemID to locate available data sources including
Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.),
STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS,
Merck, etc.) and Science Direct. OPPT's focus on these specific sources is based on their being
of high quality, highly relevant to hazard characterization, and publicly available.

OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and
Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment
Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are
presented in an international forum that involves review and endorsement by governmental
authorities around the world. OPPT is an active participant in these meetings and accepts these
documents as reliable screening-level hazard assessments.

These hazard characterizations are technical documents intended to inform subsequent decisions
and actions by OPPT. Accordingly, the documents are not written with the goal of informing the
general public. However, they do provide a vehicle for public access to a concise assessment of
the raw technical data on HPV chemicals and provide information previously not readily
available to the public.

3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Chemical Abstract Service

Sub-Category I

Registry Number

110-86-1

(CASRN)

109-06-8

108-99-6

108-89-4

68391-11-7

Sub-Category II

100-54-9

100-70-9

Sub-Category III

110-89-4

Chemical Abstract Index

Sub-Category I

Name

Pyridine

Pyridine, 2-methyl-

Pyridine, 3-methyl-

Pyridine, 4-methyl-

Pyridine, alkyl derivs.

Sub-Category II

3-Pyridinecarbonitrile

2-Pyridinecarbonitrile

Sub-Category III

Piperidine

Structural Formula

See Section 1

Sub-Category I:

CASRNs 110-86-1, 109-06-8,

108-99-6, 108-89-4 and 68391-11-7 are liquids with high water

solubility and high vapor pressure. They are expected to have high mobility in soil.

Volatilization is considered moderate based on their Henry's Law constants; however, these

compounds will partially exist as cations in the environment which will attenuate the potential to

volatilize. The rate of hydrolysis

is considered negligible. The rate of atmospheric

photooxidation is considered slow to negligible. The rate of biodegradation is considered rapid

to moderate. These chemicals are expected to have low persistence (PI) and low

bioaccumulation potential (Bl).

The acute toxicity of sub-category I is low via the oral (rats), high via the dermal (rabbits) and

moderate via the inhalation (rats) routes of exposure. The alkyl pyridines are corrosive to rabbit

skin and severely irritating to rabbit eye. CASRN 110-86-1 is not a skin sensitizer in guinea pigs.

Oral repeated-dose studies with CASRN 110-86-1 in rats showed systemic toxicity ranging from

changes in body weights to histopathological changes in the liver at 33 mg/kg-bw/day; the

NOAEL was 14 mg/kg-bw/day.

In mice, repeated oral exposures showed effects on body

weight gain and liver at 200 mg/kg-bw/day; the NOAEL for systemic toxicity was 100 mg/kg-

bw/day. Repeated inhalation exposures of male rats to CASRN

108-99-6 showed no effects at the highest concentration tested; the NOAEC for systemic toxicity

was 1.10 mg/L. Repeated inhalation exposures of rats to CASRN 109-06-8 showed no effects at

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

the highest concentration tested; the NOAEC for systemic toxicity was 0.38 mg/L. Effects were
observed on body weights and liver; the NOAEC for systemic toxicity was not established. No
specific reproductive toxicity studies were available but effects on the male reproductive system
were observed after repeated oral exposures to CASRN 110-86-1 in mice and rats. No
developmental toxicity studies were available. Sub-category I did not induce gene mutations in
vitro. CASRN 110-86-1 did not induce chromosomal aberrations in vitro or in vivo. In two-year
bioassays in rats and mice exposed via drinking water, CASRN 110-86-1 increased the incidence
of tumors.

The acute hazard to fish is based on the toxicity values for CASRNs 108-89-4, 108-99-6,
109-06-8, 110-86-1 and 68391-11-7 ranging from 40 to 897 mg/L. The acute hazard to aquatic
invertebrates is based on the toxicity values for CASRNs 108-99-6, 110-86-1 and 68391-11-7
ranging from 69 to 2470 mg/L. The acute hazard to aquatic plants is based on the toxicity value
for CASRN 108-99-6 of 320 mg/L.

The reproductive and developmental toxicity endpoints remain as data gaps under the HPV
Challenge Program.

Sub-Category II:

CASRNs 100-54-9 and 100-70-9 are solids at ambient temperature with high water solubility
and moderate vapor pressure. They are expected to have high mobility in soil. Volatilization is
considered moderate based on their Henry's Law constants. The rates of hydrolysis and
atmospheric photooxidation are considered negligible. The rate of biodegradation is considered
rapid to moderate and they are expected to have low persistence (PI) and low bioaccumulation
potential (Bl).

The acute toxicity of sub-category II is low via the oral (rats) and dermal (rabbits) routes of
exposure. Repeated oral exposures with CASRN 100-54-9 in rats showed histopathological
changes in the liver at 30 mg/kg-bw/day; the NOAEL for systemic toxicity was 5 mg/kg-bw/day.
At higher doses, there was necrosis of spermatocytes and spermatids. No specific reproductive
toxicity studies were available but effects on the male reproductive system were observed after
repeated oral exposures to CASRN 100-54-9 in rats. No developmental toxicity studies were
available. CASRN 100-54-9 did not induce gene mutations or chromosomal aberrations in vitro.

The acute hazard to fish is based on the toxicity value for CASRN 100-70-9 of 726 mg/L. The
acute hazard to aquatic invertebrates is based on the estimated toxicity values for CASRNs
100-54-9 and 100-70-9 of 1000 mg/L. The acute hazard to aquatic plants is based on the
estimated toxicity values for CASRNs 100-54-9 and 100-70-9 of 232 mg/L.

The reproductive and developmental toxicity, and the acute toxicity to aquatic invertebrates and
aquatic plants endpoints remain as data gaps under the HPV Challenge Program.

Sub-Category III:

CASRN 110-89-4 is a colorless liquid with high water solubility and high vapor pressure. It is
expected to have moderate mobility in soil. Volatilization of CASRN 110-89-4 is considered
moderate based on its Henry's Law constant; however, it is a weak base that is expected to exist
as a cation in water and cations do not volatilize. The rate of hydrolysis is considered negligible.

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

The rate of atmospheric photooxidation is considered moderate. CASRN 110-89-4 was found to
be readily biodegradable and is expected to have low persistence (PI) and low bioaccumulation
potential (Bl).

The acute oral toxicity of CASRN 110-89-4 is moderate in rats and low in mice. Acute dermal
toxicity in rabbits and inhalation toxicity in rats is moderate. CASRN 110-89-4 is corrosive to
rabbit skin, severely irritating to rabbit eye and a skin sensitizer in guinea pigs. After repeated
inhalation exposures, no adverse effects were observed in rats at the highest dose tested; the
NOAEC for systemic toxicity was 0.348 mg/L. No data were available for the reproductive
toxicity endpoint. In a prenatal developmental toxicity study in rats via the inhalation route,
dams showed decreased weight gains at 0.015 mg/L; the NOAEC for maternal toxicity was
0.003 mg/L. Fetal body weights were decreased at 0.003 mg/L. The NOAEC for developmental
toxicity was not established. CASRN 110-89-4 did not induce gene mutations
in vitro and did not induce micronuclei in vivo. No data were available for the chromosomal
aberrations endpoint. In a two-year bioassay in rats exposed via drinking water, CASRN
110-89-4 did not increase the incidence tumors.

The acute hazard to fish is based on the estimated toxicity value for CASRN 110-89-4 of 46
mg/L. The acute hazard to aquatic invertebrates is based on the estimated toxicity value for
CASRN 110-89-4 of 4 mg/L. The acute hazard to aquatic plants is based on the estimated
toxicity values for CASRN 110-89-4 of 1.2 mg/L.

The reproductive toxicity and the acute toxicity to fish, aquatic invertebrates and aquatic plants
endpoints remain as data gaps under the HPV Challenge Program.

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

The sponsor, the American Chemistry Council's Pyridine and Pyridine Derivatives High
Production Volume Work Group, submitted a Test Plan and Robust Summaries to EPA for the
Pyridine and Pyridine Derivatives category on December 17, 2003. EPA posted the submission
on the ChemRTK HPV Challenge website on January 28, 2004

(http://www.epa.gov/chemrtk/pubs/summaries/pyriderv/cl4925tc.htm). EPA comments on the
original submission were posted to the website on July 15, 2004. Public comments were also
received and posted to the website. The pyridine and pyridine derivatives category consists of
eight substances described in Section 1.

Category Justification

The pyridine and pyridine derivatives category was submitted comprising nine chemicals that are
structurally-related derivatives of pyridine: piperidine is the saturated ring structure derivative of
pyridine. The sponsor grouped the chemicals into one category based on similarities in structure
and functional features and similar or predictable physical-chemical, environmental fate,
ecotoxicity and mammalian toxicities. Two of the sponsored substances are mixtures; pyridine,
alkyl derivatives (CASRN 68391-11-7) and pyridinium, l-(phenylmethyl)-ethyl methyl
derivatives, chlorides (CASRN 68909-18-2) for which the sponsor did not provide the
composition.

EPA did not support the category formation as submitted because of significant differences in the
chemical structures, in the metabolism of some of the category members and a lack of evidence
of their similar mammalian toxicities. In addition, it was questionable whether data for the
alkylpyridines could be read across to the alkylpyridine derivatives or pyridinium chlorides
because composition for these mixtures is unknown. The sponsor did not provide a category
justification for the ecotoxicity endpoints; however, EPA concluded that the observed differences
in structures are also likely to lead to differences in ecological toxicity. In its letter (to Charlie
Auer), dated November 15, 2006, the sponsor withdrew the sponsorship for pyridinium,
l(phenylmethyl)- Et Me derivs., chlorides (CASRN 68909-18-2). For the remaining category
members, EPA proposed grouping of the chemicals into the following sub-categories:

Sub-category I: pyridine (CASRN 110-86-1), 2-picoline (CASRN 109-06-8), 3-picoline
(CASRN 108-99-6), 4-picoline (CASRN 108-89-4) and pyridine, alkyl derivatives (CASRN
68391-11-7);

Sub-category II: nicotinonitrile (CASRN 100-54-9) and picolinonitrile (CASRN 100-70-9); and
Sub-category III: Piperidine (CASRN 110-89-4)

The Sponsor agreed with EPA's suggested sub-categories and EPA agrees that the sub-categories
of the pyridine and pyridine derivatives category are acceptable but read-across between the sub-
categories is not supported.

6

------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2009 1 Chemical Identity 1.1 Identification and Purity The following description is taken from the Test Plan (2003): Pyridine and pyridine derivatives are industrial solvents and chemical intermediates. CASRN 68391-11-7 is a TSCA unknown of variable composition or of biological origin (UVCB) chemical which has an unspecified molecular formula and weight. The chemical structures are presented in Table 1. 'I'iihie 1. Chemical Structures of Pyridine and Pyridine Derivatives Chemical Name C'ASUN Structure Pyridine 110-86-1 O 2-Picoline 109-06-8 (T^i N 3-Picoline 108-99-6 4-Picoline 108-89-4 -O Pyridine, alkyl derivatives 68391-11-7 Representative structure: KV ^—N Picolinonitrile 100-70-9

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

'I'iihie 1. Chemiciil Structures of Pyridine niul Pyridine Derivatives

Chemiciil N;ime

C'ASUN

Structure

Nicotinonitrile

100-54-9

—G

N	N

Piperidine

110-89-4



1.2 Physical-Chemical Properties
Sub-Category I

The physical-chemical properties of the pyridine and alkylpyridines sub-category are
summarized in Table 2. The pyridine and alkylpyridines sub-category primarily contains liquids
with high water solubility and high vapor pressure.

Sub-Category II

The physical-chemical properties of picolinonitrile and nicotinonitrile are summarized in
Table 3. Picolinonitrile and nicotinonitrile are solids at ambient temperature with high water
solubility and moderate vapor pressure.

Sub-Category III

The physical-chemical properties of piperidine are summarized in Table 4. Piperidine is a
colorless liquid with high water solubility and high vapor pressure.

8

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Table 2. Physical-C

lemical Properties Sub-Category I1

Property

Pyridine

2-Picoline

3-Picoline

4-Picoline

Pyridine, alkyl
derivs.

CASRN

110-86-1

109-06-8

108-99-6

108-89-4

68391-11-7

Molecular Weight

79

93

93

93

UVCB2

Physical State

Liquid

Liquid

Liquid

Liquid

No data2

Melting Point

-41.6°C
(measured)

-70 to -66.8°C
(measured)

-18.3°C
(measured)

3.66°C (measured)

No data2

Boiling Point

115.2°C

128-129°C

143-144°C

144.9-145°C

No data2



(measured)

(measured)

(measured)

(measured)



Vapor Pressure

20 mm Hg at 25°C

10-12.6 mm Hg at

5.32 mm Hg at

7.99 mm Hg at

No data2



(measured)

25°C (measured)

25°C (estimated);
6.05 mm Hg at
25°C (measured)3

25°C (measured)



Water Solubility

1*106 mg/L,
miscible

lxlO6 mg/L, freely
soluble, very

lxlO6 mg/L,
miscible

lxlO6 mg/L,
soluble, infinite

No data2



(measured)

soluble, miscible
(measured)

(measured)

solubility, miscible
(measured)



Dissociation

5.23 (measured)3

6.00 (measured)3

5.63 at 25°C

5.98 at 25°C

No data2

Constant (pKa)





(measured)

(measured)



Henry's Law

1.1 xlO"5 atm-

9.96x10 6 atm-

7.73x10 6 atm-

6.0xl0"6 atm-

No data2

Constant

m3/mole

m3/mole

m3/mole

m3/mole





(measured)

(measured)

(measured)

(measured)



Log Kow

0.64 (measured)

1.11 (measured)

1.35 (estimated);
1.20 (measured)3

1.22 (measured)

No data2

'The American Chemistry Council's Pyridine and Pyridine Derivatives HPV Work Group. December 19, 2003. Revised Robust Summary for the Pyridine and
Pyridine Derivatives Category, http://www.epa.gov/chemrtk/pubs/summaries/pvriderv/cl4925tc.htm.

2UVCB chemicals, which are TSCA Unknown, of Variable Composition, or of Biological Origin, have unspecified molecular formulas and molecular weights.
According to the Robust Summary, properties are not calculable for UVCB chemicals.

3HSDB. 2008. Hazardous Substances Data Bank. Accessed December 17, 2008. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.

9

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Table 3. Physical-Chemical

Properties of Sub-Category II



Property

Picolinonitrile

Nicotinonitrile

CASRN

100-70-9

100-54-9

Molecular Weight

104

104

Physical State

Solid at ambient temperature

Solid at ambient temperature

Melting Point

29°C (measured)

50°C (measured)

Boiling Point

222°C (measured)

240°C (measured)

Vapor Pressure

0.102 mm Hg at 25°C

0.0262 mm Hg at 25°C



(estimated)

(estimated);

0.296 mm Hg at 25°C

(measured)2

Water Solubility

35,710 mg/L at 25°C
(estimated)

27,920 mg/L at 25°C (estimated);
1.35x10s mg/L at 20°C
(measured)2

Dissociation Constant (pKa)

-0.26 (measured)2

1.39 (measured)2

Henry's Law Constant

6.8x1 0"8atm-m3/mole

2.7*10~7 at 111-111/111 ole



(estimated);
3.4x10"7atm-m3/mole

(measured)2



(estimated)3



Log Kow

0.35 (estimated);
0.45 (measured)2

0.35 (estimated);
0.36 (measured)2

The American Chemistry Council's Pyridine and Pyridine Derivatives HPV Work Group. December 19, 2003. Robust
Summary and Test Plan for Pyridine and Pyridine Derivatives.
http: //www.epa. go v/chemrtk/pubs/ summaries/pvriderv/c 14925tc .htm.

2SRC. The Physical Properties Database (PHYSPROP). Syracuse, NY: Syracuse Research Corporation. Available from
http://www.svrres.com/esc/phvsprop.htm as of December 2008.

3USEPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States Environmental
Protection Agency, Washington, DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

Table 4. Physical-Chemical Properties of Sub-Category III1

Property

Piperidine

CASRN

110-89-4

Molecular Weight

85.2

Physical State

Colorless liquid

Melting Point

-11.03°C (measured)

Boiling Point

106.3°C (measured)

Vapor Pressure

32.1 mm Hg at 25°C (measured)

Water Solubility

lxlO6 mg/L at 20°C (measured)

Dissociation Constant (pKa)

11.28 (measured)2

Henry's Law Constant

4.4xl0"6 atm-m3/mole (measured)2

Log Kow

0.84 (measured)

'The American Chemistry Council's Pyridine and Pyridine Derivatives HPV Work Group. December 19, 2003. Robust
Summary and Test Plan for Pyridine and Pyridine Derivatives.
http://www.epa.gov/chemrtk/pubs/summaries/pvriderv/cl4925tc.htm.

SRC. The Physical Properties Database (PHYSPROP). Syracuse, NY: Syracuse Research Corporation. Available from
http://www, svrres.com/esc/phvsprop.htm as of October 15, 2008.

General Information on Exposure

10

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

2.1 Production Volume and Use Pattern

The Pyridine and Pyridine Derivatives Category chemicals had an aggregated production and/or
import volume in the United States of 35 million to 200 million pounds during the calendar year

Non-confidential information in the IUR indicated that the industrial processing and uses of
these chemicals include intermediates and corrosion inhibitors and anti-scaling agents. Non-
confidential information in the IUR indicated that the commercial and consumer products
containing the chemical under CASRN 68391-11-7 include "other." IUR information also
indicates there were no commercial/consumer uses for other chemicals in the category. The
HPV submission for this category states that the chemicals are used as industrial solvents and
chemical intermediates in the production of drugs and vitamins, as well as industrial products
such as paints, dyes, rubber products and adhesives. In addition, the HSDB states that
CASRN 110-86-1 and 110-89-4 are used in food flavorings.

2.2 Environmental Exposure and Fate

There is potential for environmental releases of these chemicals to various media including
water, land and air.

Sub-Category I

The environmental fate properties are provided in Table 5. The pyridine and alkylpyridines
category contains liquids with high water solubility and high vapor pressure. The pyridine and
alkylpyridines are expected to have high mobility in soil. Volatilization of the pyridine and
alkylpyridines is considered moderate based on their Henry's Law constants; however, these
compounds will partially exist as cations in the environment which will attenuate the potential to
volatilize. The rate of hydrolysis is considered negligible. The rate of atmospheric
photooxidation is considered slow to negligible. The rate of biodegradation is considered rapid
to moderate. Pyridine and alkylpyridines are expected to have low persistence (PI) and low
bioaccumulation potential (Bl).

Table 5. Environmental Fate Characteristics of Sub-Category I1

2005.

CASRN 100-54-9
CASRN 100-70-9
CASRN 108-89-4
CASRN 108-99-6
CASRN 109-06-8
CASRN 110-86-1
CASRN 110-89-4
CASRN 68391-11-7

1 to 10 million pounds
1 to 10 million pounds
1 to 10 million pounds
10 to 50 million pounds
10 to 50 million pounds
10 to 50 million pounds
1 to 10 million pounds
1 to 10 million pounds

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009











Pyridine,

Property

Pyridine

2-Picoline

3-Picoline

4-Picoline

alkyl derivs.

CASRN

110-86-1

109-06-8

108-99-6

108-89-4

68391-11-7

Photodegradation

28.9 days

9.707 days

9.707 days

9.707 days

No data2

Half-life

(estimated)

(estimated)

(estimated)

(estimated)



Hydrolysis Half-

Stable

Stable

Stable

Stable

Stable

life

(estimated)

(estimated)

(estimated)

(estimated)

(estimated)

Biodegradation

11-15% after 14

100% after 9

85% after 29

68-100% in 24

No data2



days

days with

days

days by soil





58-97% after 28

benzoate

95% after 10

suspension





days 0% after

100% after 13

days

90% after 14





19 days

days with

45% after 30

days in river





100% after 21

glucose

days by soil

water





days

94% after 7 days

suspension

100% in 66-170





98% after 13

56- 100% in 24

100% after 14

days by soil





days

days by soil

days by river

suspension





100% after 8

suspension.

water

30% in 7 days at





days at 20 mg/L

1-2% in 28 days

100% after 9

20 mg/L





in river water

(not readily

days with

100% in 32 days





92-100% in 28

biodegradable)3

benzoate

by soil





days (readily



100% after 48

suspension





biodegradable)3



days with











glucose











3-12% in 28











days (not readily











biodegradable)3





Bioconcentration

BCF = 3

BCF = 1

BCF = 2

BCF = 2

No data2



(estimated)4

(estimated)4

(estimated)4

(estimated)4



Log Koc

1.5 (estimated)4

1.7 (estimated)4

1.7 (estimated)4

1.7 (estimated)4

No data2

Fugacity









No data2

(Level III











Model)4

9.52%

5.5%

5.12%

4.87%



Air

42.9%

46.3%

45.1%

44.8%



Water

47.5%

48.1%

49.7%

50.2%



Soil

0.0818%

0.1%

0.1%

0.1%



Sediment











Persistence5

PI (low)

PI (low)

PI (low)

PI (low)

No data

Bioaccumulation5

B1 (low)

B1 (low)

B1 (low)

B1 (low)

No data

The American Chemistry Council's Pyridine and Pyridine Derivatives HPV Work Group. December 19, 2003. Revised Robust
Summary for the Pyridine and Pyridine Derivatives Category.
http: //www.epa. gov/chemrtk/pubs/ summaries/pvriderv/c 14925tc .htm.

2UVCB chemicals, which are TSCA Unknown, of Variable Composition, or of Biological Origin, have unspecified molecular
formulas and molecular weights. According to the Robust Summary, properties are not calculable for UVCB chemicals.
3National Institute of Technology and Evaluation. 2002. Biodegradation and Bioaccumulation of the Existing Chemical
Substances under the Chemical Substances Control Law. Accessed September 18, 2008.
http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html.

4U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States Environmental
Protection Agency, Washington, DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

'Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64,
Number 213 (November 4, 1999) pp. 60194-60204.

Sub-Category II

The environmental fate properties are provided in Table 6. CASRN 100-54-9 and CASRN 100-
70-9 are solids at ambient temperature with high water solubility and moderate vapor pressure.
Both compounds are expected to have high mobility in soil. Volatilization is considered

12

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

moderate based on their Henry's Law constants. The rate of hydrolysis is considered negligible.
The rate of atmospheric photooxidation is considered negligible. The rate of biodegradation is
considered rapid to moderate. CASRN 100-54-9 and CASRN 100-70-9 are expected to have low
persistence (PI) and low bioaccumulation potential (Bl).

Table 6. Environmental Fate Characteristics of Sub-Category II1

Property

Picolinonitrile

Nicotinonitrile

CASRN

100-70-9

100-54-9

Photodegradati on
Half-life

164 days (estimated)

164 days (estimated)

Hydrolysis Half-life

Stable2

Stable2

Biodegradation

20-61% after 7 days under aerobic
conditions;

Half-life = <1 days under anaerobic
conditions

Half-life = <1 days under anaerobic
conditions;

91-97%) after 7 days under aerobic
conditions;

1% after 28 days (not readily
biodegradable)3

Bioconcentration

BCF = 3.2 (estimated)4

BCF = 3.2 (estimated)4

Log Koc

1.99 (estimated)4

1.99 (estimated)4

Fugacity

(Level III Model)

Air = 3%

Water = 34%

Soil = 63%
Sediment = <0.1%

Air = 11%

Water = 33%

Soil = 56%
Sediment = <0.1%

Persistence5

PI (low)

PI (low)

Bi oaccumul ati on5

Bl (low)

Bl (low)

'The American Chemistry Council's Pyridine and Pyridine Derivatives HPV Work Group. December 19, 2003.
Robust Summary and Test Plan for Pyridine and Pyridine Derivatives.
http://www.epa.gov/chemrtk/pubs/summaries/pvriderv/cl4925tc.htm.

2HSDB. 2008. Hazardous Substances Data Bank. Accessed December 10, 2008. http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?HSDB.

3National Institute of Technology and Evaluation. 2002. Biodegradation and Bioaccumulation of the Existing
Chemical Substances under the Chemical Substances Control Law.
http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html.

4USEPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

5Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.

Sub-Category III

The environmental fate properties are provided in Table 7. CASRN110-89-4 is expected to have
moderate mobility in soil. CASRN110-89-4 was readily biodegradable using a modified MITI
biodegradation test (OECD 301C). Volatilization of CASRN110-89-4 is considered moderate
based on its Henry's Law constant; however, it is a weak base that is expected to exist as a cation
in water and cations do not volatilize. The rate of hydrolysis is considered negligible under
environmental conditions. CASRN110-89-4 is expected to have low persistence (PI) and low
bioaccumulation potential (Bl).

13

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Table 7. Environmental Fate Characteristics of Sub-Category III1

Property

Piperidine

Photodegradation Half-life

0.12 days (estimated)

Hydrolysis Half-life

Stable

Biodegradation

67% after 14 days (readily biodegradable)2

Bioconcentration

BCF = 3.2 (estimated)3

Log Koc

1.97 (estimated)3

Fugacity

(Level III Model)

Air = 70%

Water = 16%

Soil = 14%
Sediment = <0.1%

Persistence4

PI (low)

Bi oaccumul ati on4

Bl (low)

'The American Chemistry Council's Pyridine and Pyridine Derivatives HPV Work Group. December 19, 2003.
Robust Summary and Test Plan for Pyridine and Pyridine Derivatives.
http://www.epa.gov/chemrtk/pubs/summaries/pvriderv/cl4925tc.htm.

2National Institute of Technology and Evaluation. 2002. Biodegradation and Bioaccumulation of the Existing
Chemical Substances under the Chemical Substances Control Law.
http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html.

3USEPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

4Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances.

Federal Register 64, Number 213 (November 4, 1999) pp. 60194-60204.

3 Human Health Hazard

A summary of health effects data submitted for SIDS endpoints is provided in Table 8. The table
also indicates where data for tested category members are read-across (RA) to untested members
of the category.

Acute Oral Toxicity

Sub-Category I
Pyridine (CASRN110-86-1)

(1)	Male albino rats (5/dose) were administered undiluted pyridine by the oral route at 464, 681,
1000 or 1470 mg/kg-bw and observed for 14 days. No mortality was observed at the lowest
dose. Two rats died at each mid-dose in the first seven days post exposure and all rats died
within two days at the highest dose, (http://www.srcinc.com/what-we-
do/databaseforms.aspx?id=384)

LD50 = 891 mg/kg-bw

(2)	In studies with rats and mice, the LD50 was determined (no other information available).
(http://www.srcinc.com/what-we-do/databaseforms.aspx?id=384)

LD50 = 800-1600 mg/kg-bw
4-Picoline (CASRN 108-89-4)

14

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

In two studies, Sprague-Dawley rats (4 females/dose in one study and 2-3/sex/dose in the other)
were administered 4-picoline via gavage at doses from 125 to 2000 mg/kg-bw and observed for
up to 14 days. Mortality was observed at all doses > 500 mg/kg-bw.

LD50 = 700 - 841 mg/kg-bw

3-Picoline (CASRN108-99-6)

(1)	Sprague-Dawley rats (2-3/sex/dose) were administered 3-picoline via gavage at 501, 631, 794
or 1000 mg/kg-bw and observed for seven days. Mortality was observed at all doses within four
days of dosing.

LD50 = 710 mg/kg-bw

(2)	Fischer rats (3 males/dose) were administered 3-picoline via gavage at 320, 630, 1300, 2000,
3200 or 5000 mg/kg-bw and observed for 14 days. No rats died at 320 mg/kg-bw and one rat
died at 630 mg/kg-bw. All rats died at doses greater than 630 mg/kg-bw.

LD50 = 630 mg/kg-bw

2-Picoline (CASRN 109-06-8)

In two studies, Sprague-Dawley rats (10 males/dose in one study and 2-3/sex/dose in the other)
were administered 2-picoline via gavage at doses from 550 to 1260 mg/kg-bw and observed
daily for up to 28 days. Mortality was observed at doses greater than 790 mg/kg-bw.

LD50 = 810 to > 950 mg/kg-bw

Pyridine, alkyl derivs (CASRN 68391-11-7)

Sherman-Wistar rats (5 males/dose) were administered pyridine, alkyl derivatives via gavage at
1000, 2000, 4000, 8000 or 16,000 mg/kg-bw and observed for 14 days. At 4000 mg/kg-bw and
above, all rats died; in most cases less than five to six hours post dosing.

LD50 = 2500 mg/kg-bw
Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

(1)	Sherman-Wistar rats (5 males/dose) were administered nicotinonitrile via gavage at 250, 500,
1000, 2000 or 4000 mg/kg-bw and observed for 14 days. All rats at the two high doses died
within 3 hours of exposure. Mortality was also observed at the 1000 mg/kg-bw. No rats died at
the two lower doses.

LD50 =1100 mg/kg-bw

(2)	Sprague-Dawley rats (5/sex/dose) were administered nicotinonitrile via gavage at 0, 1297,
1388, 1485, 1589 or 1700 mg/kg-bw and observed for 14 days. In males, mortality was observed
at all doses; no females dying at 1297 mg/kg-bw..

LD50 (males) = 633 mg/kg-bw
LD50 (females) = 1455 mg/kg-bw

Picolinonitrile (CASRN 100-70-9)

15

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Sprague-Dawley rats (2-3/sex/dose) were administered picolinonitrile via gavage at 500 or 1000
mg/kg-bw as a 5% solution of test substance in corn oil. Two of 3 rats from the high dose died
within three days of dosing. No mortality occurred at 500 mg/kg-bw. No other information
provided.

LD50 = not calculated

Sub-Category III
Piperidine (CASRN110-89-4)

(1)	Sprague-Dawley rats (5/sex/dose) were administered piperidine via gavage at 300, 550 or 800
mg/kg-bw and observed for 14 days. Mortality was observed (7 of 10) at the highest dose.
LD50 = 740 mg/kg-bw

(2)	Sprague-Dawley rats (5 females) were administered piperidine one at a time with the
estimated LD50 dose in an up and down method and observed for 14 days.

LD50 = 337 mg/kg-bw

(3)	Sprague-Dawley rats (10/sex/dose) were administered piperidine via gavage at 5, 50, 500 or
2000 mg/kg-bw using the fixed-dose procedure and up and down method and observed for 14
days (number of deaths not stated).

LD50 (males) = 405 mg/kg-bw
LD50 (females) = 488 mg/kg-bw

(4)	ddY Mice (10/sex/dose) were administered piperidine (doses not specified) via gavage and
observed for 14 days (number of deaths not stated).

LD50 (males) = 633 mg/kg-bw
LD50 (females) = 536 mg/kg-bw

Acute Dermal Toxicity

Sub-Category I
Pyridine (CASRN 110-86-1)

Albino rabbits (2/dose) were administered 500, 1000 or 2000 mg/kg-bw pyridine dermally on to
the hair-clipped skin under occluded conditions for 24 hours. All animals in the high dose group
died within a day post exposure. Severe chemical burn was seen topically at all doses.
1000 mg/kg-bw < LD50 < 2000 mg/kg-bw

4-Picoline (CASRN 108-89-4)

(1)	New Zealand White rabbits (4 males/dose) were administered 4-picoline dermally
(concentration not stated) on to the hair-clipped skin under occluded conditions for 24 hours and
observed for 14 days.

LD50 ~ 257 mg/kg-bw

(2)	In two similar studies, New Zealand White rabbits (1/sex/dose) were administered 4-picoline
dermally on to hair-clipped skin at 50.1 (male), 79.4 (female), 126 (male), 200 (female), 501
(male), 1000 (female) or 2000 (male) mg/kg-bw under occluded conditions for 24 hours and

16

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

observed for 14 days. In both studies, rabbits at 316 mg/kg-bw and above died within one day.
In one study, the animals also died at 126 and 200 mg/kg-bw.

79.4 mg/kg-bw < LD50 < 126 mg/kg-bw

3-Picoline (CASRN108-99-6)

(1)	New Zealand White rabbits (2/dose, sex not stated) were administered 3-picoline dermally at
200, 800 or 2000 mg/kg-bw for 24 hours and observed for 14 days. All animals at the highest
dose died.

200 mg/kg-bw < LD50 < 800 mg/kg-bw

(2)	New Zealand White rabbits (1/sex/dose) were administered 3-picoline dermally on to hair-
clipped skin at 79.4 (male), 126 (female), 200 (male), 316 (female), 501 (male), 1000 (female) or
2000 (male) mg/kg-bw under occluded conditions for 24 hours and observed for 14 days.

Rabbits at 501 mg/kg-bw and above died. Mortality was also seen at 200 mg/kg-bw.

126 mg/kg-bw < LD50 < 200 mg/kg-bw

(3)	New Zealand White rabbits (5/sex/dose) were administered 3-picoline dermally on to hair-
clipped skin at 200 and 1000 mg/kg-bw under occluded conditions for 24 hours and observed for
14 days. All animals at the higher dose died.

200 mg/kg-bw < LD50 < 1000 mg/kg-bw

2-Picoline (CASRN 109-06-8)

(1)	New Zealand White rabbits (1/sex/dose) were administered 2-picoline dermally on to clipped
hair at 79.4 (female), 200 (male), 316 (female), 501 (male), 1000 (female), or 2000 (male)
mg/kg-bw under occluded conditions and observed for 14 days post exposure. All rabbits
exposed to 316 mg/kg-bw or above died within one day of exposure.

200 mg/kg-bw < LD50 <316 mg/kg-bw

(2)	Rabbits (strain and number not reported) were administered 2-picoline (dose not stated)
dermally and observed for 14 days. No other information provided.

LD50 -385 mg/kg-bw

(3)	Rabbits (strain not stated, 2/dose) were administered 2-picoline dermally at 252 or 500
mg/kg-bw under occluded conditions for 24 hours. All animals at the higher dose died. Upon
removal of the cuff, animals in the lower dose group showed signs of moderate necrosis with
slight edema.

252 mg/kg-bw < LD50 < 500 mg/kg-bw
Pyridine, alkyl derivatives (CASRN 68391-11-7)

New Zealand White rabbits (2/sex/dose) were administered pyridine, alkyl derivatives dermally
at 0.5, 1.0 or 2.0 mL/kg-bw to abraded skin under an occluded conditions for 24 hours and
observed for 14 days. The only mortality was a female in the high dose group which died on day
12.

LD50 > 2.0 mL/kg-bw

17

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Sub-Category II

Nicotinonitrile (CASRN100-54-9)

Rabbits (2/sex/dose, strain not reported,) were administered nicotinonitrile dermally at 500,
1000, 2000, or 4000 mg/kg-bw u on to the clipped and abraded backs under occluded condition
and observed for 14 days (exposure duration not reported). All rabbits at the highest dose died.
One male at 2000 mg/kg-bw died.

2000 mg/kg-bw < LD50 < 4000 mg/kg-bw

Sub-Category III
Piperidine (CASRN 110-89-4)

New Zealand White rabbits were treated with piperidine by the dermal route of exposure and
observed for 14 days. No other information provided.
http://www.bgchemie.de/files/95/ToxBew72-L.pdf
LD50 = 276 mg/kg-bw

Acute Inhalation Toxicity

Sub-Category I
Pyridine (CASRN 110-86-1)

(1)	Sprague-Dawley rats (5/sex/concentration) were exposed (whole body) to pyridine
(concentrations not stated) for one hour.

1-h LCso-29.1 mg/L

(2)	Sprague-Dawley rats (6 males/concentration) were exposed (nose only) to pyridine at 1600,
4900 or 6000 ppm (approximately 5.18, 14.7 or 18 mg/L, respectively) for 4 hours and were
observed for 14 days. Mortality occurred at 4900 ppm (2 of 6 rats within four days) and 6000
ppm (5 of 6 rats during exposure).

14.7 mg/L < LD50 < 18 mg/L

(3)	Six rats (strain and sex not reported) were exposed to pyridine at 4000 ppm (12 mg/L) for 4
hours and were observed for 14 days. Five rats died within 14 days after exposure.

LC50 < 12 mg/L

4-Picoline (CASRN 108-89-4)

(1)	Rats (6 males, strain not reported) were exposed (whole body) to 4-picoline at an average
chamber concentration of 9.2 g/m3 (approximately 9.2 mg/L) for five hours. All animals died
during exposure.

LC50 < 9.2 mg/L

(2)	Rats (6 males, strain not reported) were exposed (whole body) to 4-picoline at an average
chamber concentration of 17.5 g/m3 (approximately 17.5 mg/L) for two and half hours. All
animals died during exposure.

2.5 h-LCso < 17.5 mg/L

(3)	Albino rats (6 males) were exposed to 4-picoline at 1000 ppm (approximately 3.8 mg/L) for 4
hours and observed for 14 days post exposure. One rat died during the study.

18

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

LC50 > 3.8 mg/L
3-Picoline (CASRN108-99-6)

(1)	Sprague-Dawley rats (6 males) were exposed (whole body) to 3-picoline at an average
chamber concentration of 11.82 g/m3 (approximately 11.8 mg/L) for 5 hours. All animals died
during exposure.

LC50 < 11.8 mg/L

(2)	Sprague-Dawley rats (6 males) were exposed (nose only) to 3-picoline at concentrations of
1300 and 3300 ppm (approximately 4.95 and 12.7 mg/L, respectively) for 4 hours. All animals
at the higher concentration died during exposure.

5.0 mg/L  ~ 6.96 mg/L

(2)	Wistar rats (number and sex/concentration not stated) were exposed via inhalation to
piperidine at 6960 or 13,920 mg/m3 (approximately 6.96 or 13.9 mg/L) for four hours and
observed for 14 days. No mortalities occurred at the lower concentration. At 13,920 mg/m3, all
rats died (http://www.bgchemie.de/files/95/ToxBew72-L.pdf).

~ 6.96 < LC50 < -13.9 mg/L

(3)	Sprague-Dawley rats of both sexes (number/dose not stated) were exposed to piperidine
(concentrations not stated) via inhalation for four hours and observed for 14 days
(http://www.bgchemie.de/files/95/ToxBew72-L.pdf).

LC50 ~ 4.8 mg/L

Repeated-Dose Toxicity

Sub-Category I
Pyridine (CASRN 110-86-1)

19

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

(1)	In a 13-week study, Sprague-Dawley rats (10/sex/dose) were administered pyridine via
gavage at 0, 0.25, 1.0, 10, 25 or 50 mg/kg-bw/day 7 days/week. No treatment-related mortalities
occurred. Males at the highest dose had statistically significant (significance not provided)
decreased body weights and weight gains and increased food consumption. Absolute and
relative liver weights were significantly increased (significance not provided) at 10, 25 and 50
mg/kg-bw/day in females. Elevated (though not significant) cholesterol levels were observed in
females at the two higher doses. Inflammatory hepatic lesions were observed in both sexes:
males at 0.25, 1.0 and 50 mg/kg-bw/day and females at 50 mg/kg-bw/day. There were no
treatment-related effects on the hematological parameters or macroscopic and microscopic
changes noted during histopathological examination of the tissues. No neuropathological lesions
were observed.

LOAEL = 50 mg/kg-bw/day (based on decreased body weights effects on liver)

NOAEL = 25 mg/kg-bw/day

(2)	In a 13-week study, Fischer F344 rats (10/sex/dose) were administered pyridine via gavage at
0, 12.5, 25, 50, 100 or 200 mg/kg-bw/day. Mortality was observed at 100 mg/kg-bw/day (1
male) and at 200 mg/kg-bw/day (1 male and two females). Decreased body weights, when
compared to controls, were noted in females at all doses (11 to 14%) and in males at and above
50 mg/kg-bw/day (13 to 41%). Gross pathological observations of the liver (doses not stated)
indicated granular visceral surfaces with depressed discolored areas. At 100 and 200 mg/kg-
bw/day, multiple foci or diffuse necrosis, hepatocytomegaly, bile duct hyperplasia and fatty
metamorphosis were noted during microscopic evaluation of the liver. A proliferation of
connective tissue forming collagenous bands altering the parenchyma was also observed. At 200
mg/kg-bw/day, focal interstitial myocarditis was also observed in both sexes.

LOAEL = 100 mg/kg-bw/day (based on reduced body weights and effects on liver)

NOAEL = 50 mg/kg-bw/day

(3)	In a 13-week NTP study, Fischer F344 rats (10/sex/concentration) were administered
pyridine via drinking water at 0, 50, 100, 250, 500 or 1000 ppm (equivalent to 0 and
approximately 5, 10, 25, 55 or 90 mg/kg-bw/day) for 13 weeks. Mortality was observed at the
highest dose (2 females). Body weights were significantly (p<0.01) depressed at the two highest
doses. Clinical chemistry at these doses indicated increases in serum alanine aminotransferase
(ALT) and sorbitol dehydrogenase (SDH) activity as well as increased bile acid concentrations.
The estrous cycle length at the highest dose was longer than controls. Significantly increased
(p<0.01) absolute and relative liver weights were seen in both sexes at 25 mg/kg-bw/day and
above. Incidences of centrilobular degeneration, hypertrophy, chronic inflammation and
pigmentation were also increased at the two highest doses in both sexes. Kidney lesions in males
at the two highest doses included protein casts, chronic inflammation and mineralization. The
incidences of granular casts and hyaline degeneration (hyaline droplets) were increased in males
of the two high doses; these lesions were consistent with alpha 2|i-globulin nephropathy.

LOAEL ~ 55 mg/kg-bw/day (based on effects on body weight and liver effects)

NOAEL ~ 25 mg/kg-bw/day

(4)	In a 13-week NTP study, Wistar rats (10 males/concentration) were administered pyridine via
drinking water at 0, 50, 100, 250, 500 or 1000 ppm (0 and approximately 5, 10, 30, 60 or 100
mg/kg-bw/day) pyridine. Mortality was observed at 60 mg/kg-bw/day (one male). Body

20

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

weights and body weight gains were significantly decreased (p<0.01) at 30 mg/kg-bw/day and
above. Clinical chemistry at the two highest doses indicated increases in serum alanine
aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activity and increased bile acid
concentrations. In the liver, incidences of centrilobular degeneration, hypertrophy, chronic
inflammation and pigmentation were generally increased at the two highest doses.

LOAEL ~ 60 mg/kg-bw/day (based on changes in clinical chemistry and effects on liver)
NOAEL ~ 30 mg/kg-bw/day

(5)	In a two-year drinking water study, described in the carcinogenicity section, Fischer 344 rats
(50/sex/dose) were exposed to pyridine in drinking water at 0, 100, 200 or 400 ppm (0 and
approximately 7, 14 or 33 mg/kg-bw/day). Treatment-related non-neoplastic lesions were
observed in the liver of both sexes at 400 ppm (-33 mg/kg-bw/day). These included centrilobular
cytomegaly, cytoplasmic vacuolization, periportal fibrosis, fibrosis, centrilobular degeneration
and necrosis and pigmentation.

LOAEL ~ 33 mg/kg-bw/day (based on liver effects)

NOAEL ~ 14 mg/kg-bw/day

(6)	In a two-year drinking water study, described in the carcinogenicity section, male Wistar rats
(50/sex/dose) were exposed to pyridine in drinking water at 0, 100, 200 or 400 ppm (0 and
approximately 8, 17 or 36 mg/kg-bw/day). Survival of rats exposed to 200 or 400 ppm was
significantly less than that of controls. Severity of nephropathy was marked in all groups and
additional evidence of systemic toxicity, including mineralization in the glandular stomach,
parathyroid gland hyperplasia and fibrous osteodystrophy was observed at 200 and 400 ppm.
Incidences of hepatic centrilobular degeneration and necrosis, fibrosis, periportal fibrosis and/or
pigmentation were increased (significance not stated) in exposed groups.

LOAEL ~ 17 mg/kg-bw/day (based on mortality and systemic effects)

NOAEL ~ 8 mg/kg-bw/day

(7)	In a four-day study, Fischer 344 rats (5 males/dose) were exposed (nose only) to pyridine at 5
or 444 ppm (approximately 0.02 or 1.44 mg/L) for 6 hours/day. Olfactory epithelial lesions in
rats exposed to both concentrations of pyridine included vacuolar degeneration of sustentacular
cells; focal, marked attenuation of the epithelium; loss of neurons and the presence of
intraepithelial luminal structures.

LOAEC ~ 0.02 mg/L (based on lesions in the olfactory epithelium)

NOAEC ~ not established

(8)	In a 13-week study, B6C3F1 mice (10/sex/dose) were administered pyridine via gavage at 25,
50, 100, 200 or 400 mg/kg-bw/day, five days/week. Six males at 400 mg/kg-bw/day and one
male in the 200 mg/kg-bw/day group died during exposure. Males in all exposure groups
experienced body weight depression (6 to 40%) in a dose-dependant manner. Males at 400
mg/kg-bw/day were lethargic or moribund and females were emaciated. At 400 mg/kg-bw/day,
some males and females had prominent lobular markings in the livers. These coincided with
histopathological changes in some animals at 200 mg/kg-bw/day and above. The hepatic lesions
consisted of fatty metamorphosis, hepatocytomegaly and multifocal necrosis and occasional
parenchymal degeneration, indicated by an increase in the number of normal mitotic figures.
LOAEL = 200 mg/kg-bw/day (based on mortality and effects on liver)

21

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

NOAEL = 100 mg/kg-bw/day

(9) In a 13-week National Toxicology Program (NTP) study, B6C3F1 mice
(10/sex/concentration) were administered pyridine in drinking water at 0, 50, 100, 250, 500 or
1000 ppm (0, 10, 20, 50, 85 or 160 mg/kg-bw/day for males and 0, 10, 20, 60, 100 or 190 mg/kg-
bw/day for females). One female mouse in the 60 mg/kg-bw/day group died during week 2. The
final mean body weights and body weight gains of females were significantly (p<0.01) reduced
at the highest dose. Sperm motility was significantly decreased (p<0.01) in exposed mice
relative to controls. Absolute and relative liver weights were increased in males at 20 mg/kg-
bw/day and higher (p<0.01) and in females at 60 and 100 mg/kg-bw/day and higher (p<0.01).
No treatment-related lesions were observed in either sex.

NOAELmaies = 160 mg/kg/bw/day (based on no treatment-related effects at highest dose tested)
LOAELfemaies = 190 mg/kg-bw/day (based on decreased body weight gain)

NOAELfemaies = 100 mg/kg-bw/day

3-Picoline (CASRN108-99-6)

In a two-week study, Sprague-Dawley rats (10 males/dose) were exposed (nose only) to
3-picoline at 0 or 290 ppm (0 or 1.10 mg/L) for 6 hours/day, 5 days/week. Five rats were
allowed to recover for 13 days post exposure. No clinical signs of toxicity were observed during
exposure. The exposed rats had changes in liver weights which were not present after the
recovery period. No other treatment-related effects were observed. No treatment-related effects
were observed on hematological or clinical chemistry analysis.

NOAEC ~ 1.10 mg/L

2-Picoline (CASRN 109-06-8)

In a six-month study, Sprague-Dawley rats (10/sex/dose) were exposed to 2-picoline vapor at 0,
5, 35, 100 ppm (0 and approximately 0.019, 0.133 or 0.38 mg/L/day) for 6 hours/day, 5
days/week. No signs of treatment-related toxicity were observed at any treatment level at any
time.

NOAEC ~ 0.38 mg/L
Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

In a 28-day study, Sprague-Dawley rats (6/sex/dose) were administered nicotinonitrile via
gavage at 0, 5, 30 or 180 mg/kg-bw/day. Additional groups of control and high dose animals
were allowed to recover for 14 days post exposure. At 180 mg/kg-bw/day significant (p<0.05)
decreased body weight gain was observed. Changes in urinalysis parameters (volume increased,
osmotic pressure decreased, changes in pH and specific gravity) in both sexes at the highest dose
were reversible. Changes in hematological parameters (increased leukocyte count, decreased
erythrocyte count) were observed at the highest dose in both sexes. Histopathological
examination showed hemosiderin deposits in the red pulp of the spleen in both sexes at the
highest dose. However, these changes were not considered toxicologically significant because
they were within normal physiological limits. Changes (significance not stated) in blood
chemistry values (increases in total protein, albumin, A/G ratio, GPT, total cholesterol and
phospholipids) were not altered during the recovery period. Treatment-related (significance not
stated) changes in relative kidney and liver weights were observed in both sexes at the highest

22

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

dose. Males at this dose also exhibited increased absolute and relative adrenal weights which did
not correlate to any histological changes. For females, kidney and liver weight changes
(significance not stated) were observed at 30 mg/kg-bw/day. Histopathology indicated
centrilobular hypertrophy of hepatocytes in both sexes at 30 mg/kg-bw/day and higher. These
were present after recovery at the highest dose in both sexes. In males, the incidence of hyaline
droplets increased in the proximal tubules at 30 mg/kg-bw/day and higher. There was also
hypertrophy of zona hepatoblast of the adrenal and extramedullar hematopoiesis and
hemosiderin deposits in spleen at the highest dose in both sexes.

LOAEL = 30 mg/kg-bw/day (based on effects on the liver)

NOAEL = 5 mg/kg-bw/day

Sub-Category III
Piperidine (CASRN110-89-4)

In a 28-day study, Wistar rats (10/sex/concentration) were exposed via inhalation (whole-body)
to piperidine at 5, 20 or 100 ppm (approximately 0.017, 0.07 or 0.348 mg/L, respectively) for six
hours/day five days/week. No treatment-related changes were observed at the two lower
concentrations. At the highest concentration, there was a slight increase in relative liver weights
and decrease in body weight gain. The increase in liver weights was significant in females but no
histopathologic correlation was observed. No differences from control were observed in
hematology, clinical chemistry, ophthalmology, pathology or histopathology. No evidence of
neurotoxicity was observed (http://www.bgchemie.de/files/95/ToxBew72-L.pdf).

NOAEL ~ 0.348 mg/L (based on no adverse effects at highest concentration tested)

Reproductive Toxicity

Sub-Category I
Pyridine (CASRN 110-86-1)

Data from an oral repeated-dose study in mice, described above, indicate effects on sperm
motility in mice. These data are inadequate to address the reproductive toxicity endpoint for the
purposes of the HPV Challenge Program. The reproductive toxicity endpoint remains a data gap
sub-category I under the HPV Challenge Program.

Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

Data from an oral repeated-dose study in rats, described above, showed necrosis of
spermatocytes and spermatids, and vacuolation of the Sertoli cells. These data are inadequate to
address the reproductive toxicity endpoint for the purposes of the HPV Challenge Program. The
reproductive toxicity endpoint remains a data gap for sub-category II under the HPV Challenge
Program.

Sub-Category III
Data gap.

Developmental Toxicity
Sub-Category I

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Data gap.

Sub-Category II
Data gap.

Sub-Category III
Piperidine (CASRN110-89-4)

Pregnant rats were exposed to piperidine at 0, 3, 15 or 100 mg/m3 (approximately 0, 0.003, 0.015
or 0.10 mg/L, respectively) via inhalation for three different exposure scenarios: throughout
pregnancy, day 4 (3 and 100 mg/m3 only) of gestation or day 9 of gestation. There was a
treatment-related decrease in body weight gain in the maternal animals at the two higher
exposure concentrations. There was a treatment-related decrease in fetal body weight with
increasing exposure concentrations and exposure times; only the low dose groups being affected
during the one day exposures.

LOAEL (maternal) ~ 0.015 mg/L (based on decrease in weight gain)

NOAEL (maternal) ~ 0.003 mg/L

LOAEL (developmental toxicity) ~ 0.003 mg/L (based on reduced fetal body weight)

NOAEL (developmental toxicity) ~ not established

Genetic Toxicity — Gene Mutation

In vitro

Sub-Category I
Pyridine (CASRN 110-86-1)

(1)	In seven reverse-mutation bacterial assays, Salmonella typhimurium strains (TA98, TA100,
TA102, TA1535, TA1537 and/or TA1538) were exposed to pyridine at concentrations ranging
from 0.05 to 100 |iL/plate with and without metabolic activation. Positive and negative controls
were tested concurrently; however, their responses were not provided. Cytotoxicity was
observed in two assays at 25 and 50 |iL/plate. No mutagenicity was observed in the presence or
absence of metabolic activation in these assays.

Pyridine was not mutagenic in these assays.

(2)	Escherichia coli strains 343/113 polA+ and KMBL1787 polA" were exposed to pyridine at
10 |ig/plate without metabolic activation. The positive control showed appropriate response.
Pyridine was not mutagenic in this assay.

(3)	Chinese hamster lung cells (V79) were exposed to pyridine at concentrations up to
9.25 |iL/mL without metabolic activation. Positive and negative controls were tested
concurrently; however, the results were not provided. Cytotoxic concentration was observed at
8.75 |iL/mL. The test substance was not mutagenic under these test conditions.

Pyridine was not mutagenic in this assay.

4-Picoline (CASRN 108-89-4)

(1) In three reverse-mutation bacterial assays, Salmonella typhimurium strains TA98, TA100, TA
1535, TA 1537, TA1538 were exposed to 4-picoline at concentrations up to 5000 |ig/plate with

24

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

and without metabolic activation. Positive and negative controls were tested concurrently;
however, the results were not provided. The test substance was not mutagenic under these test
conditions in the presence or absence of metabolic activation.

4-Picoline was not mutagenic in this assay.

(2) Chinese hamster lung cells (V79) were exposed to 4-picoline at concentrations up to
4.5 |iL/mL without metabolic activation. Positive and negative controls were tested
concurrently; however, the results were not provided. Cytotoxic concentration was 4.5 |iL/mL.
The test substance was not mutagenic under these test conditions.

4-Picoline was not mutagenic in this assay.

3-Picoline (CASRN108-99-6)

(1) In four reverse-mutation bacterial assays, Salmonella typhimurium strains TA97, TA98,
TA100, TA102, TA 1535 and/or TA 1537 were exposed to 3-picoline at concentrations up to
5000 |ig/plate with and without metabolic activation. Positive and negative controls were tested
concurrently; however, the results were not provided. The test substance was not cytotoxic or
mutagenic under these test conditions in the presence or absence of metabolic activation.
3-Picoline was not mutagenic in this assay.

(2) Chinese hamster lung cells (V79) were exposed to 3-picoline at concentrations up to

4.0 |iL/mL without metabolic activation in a mammalian cell forward mutation assay. Positive
and negative controls were tested concurrently; however, the results were not provided.
Cytotoxic concentration was 4.0 |iL/mL. The test substance was not mutagenic under these test
conditions.

3-Picoline was not mutagenic in this assay.

2-Picoline (CASRN 109-06-8)

(1) In a reverse-mutation bacterial assay, Salmonella typhimurium strains TA97, TA98, TA100,
TA102, TA 1535 and/or TA 1537 were exposed to 2-picoline at concentrations up to 5000
|ig/plate with and without metabolic activation. Positive and negative controls were tested
concurrently; however, the results were not provided. The test substance was not cytotoxic or
mutagenic under these test conditions in the presence or absence of metabolic activation.
2-Picoline was not mutagenic in this assay.

(2) Chinese hamster lung cells (V79) were exposed to 2-picoline at concentrations up to
5.5 |iL/mL without metabolic activation. Positive and negative controls were tested
concurrently; however, the results were not provided. Cytotoxic concentration was 5.25 |iL/mL.
The test substance was not mutagenic under these test conditions.

2-Picoline was not mutagenic in this assay.

Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

In reverse-mutation bacterial assays, Salmonella typhimurium strains TA98, TA100, TA1535,
TA1537 and Escherichia colifWP2 uvrA were exposed to nicotinonitrile at concentrations up to
5000 |ig/plate with and without metabolic activation. Positive and negative controls were tested
concurrently; however, the results were not provided. No cytotoxicity or mutagenicity was
observed in the presence or absence of metabolic activation.

Nicotinonitrile was not mutagenic in this assay.

Sub-Category III
Piperidine (CASRN110-89-4)

(1) In a reverse-mutation bacterial assay, Salmonella typhimurium strains TA98, TA100,

TA1535 and TA1537 were exposed to piperidine at a concentration of 3 |imol/plate, with and
without metabolic activation. The controls behaved as expected. Piperidine was negative for
mutagenesis in this assay in the presence or absence of metabolic activation.

Piperidine was not mutagenic in this assay.

(3) Escherichia coli strains 343/113 polA+ and KMBL1787 polA" were exposed to piperidine at
10 |ig and 40 mM without metabolic activation. The positive control behaved appropriately. At
the lower concentration the results were inconclusive but at the higher concentration, the results
were negative.

Piperidine was not mutagenic in this assay.

(3) Mouse lymphoma L5178Y/TK+ cells were examined for mutations following exposure to 0,
2.00, 4.01 or 6.01 mM piperidine in the absence of metabolic activation and 0, 2.00, 4.01, 6.01 or
8.02 mM piperidine in the presence of metabolic activation. The cytotoxic concentration was
6.01 mM with activation and 8.02 mM with activation. No mutagenic activity was observed in
the presence of metabolic activation. With metabolic activation, piperidine was positive for
mutagenicity.

Piperidine was mutagenic in this assay in the absence of metabolic activation and not
mutagenic in the presence of metabolic activation.

Genetic Toxicity — Chromosomal Aberrations

In vitro

Sub-Category I
Pyridine (CASRN 110-86-1)

(1) Chinese hamster fibroblast cells (CHL) were exposed to pyridine at concentrations up to
505.7 mg/mL without metabolic activation. Negative controls were tested concurrently;
however, the results were not provided. Based on the criteria for the assay, pyridine did not
cause an increase in chromosomal aberrations.

Pyridine did not induce chromosomal aberrations in this assay.

(2) Chinese hamster ovary (CHO) cells were exposed to pyridine concentrations up to

2325 |ig/mL without metabolic activation and 5000 |ag/m L with metabolic activation. Positive
and negative controls were tested concurrently; however, the results were not provided.
Cytotoxicity occurred at concentrations >2325 |ag/mL without metabolic activation and

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

>5000 |ig/mL with metabolic activation. Pyridine did not induce chromosomal aberrations with
or without metabolic activation.

Pyridine did not induce chromosomal aberrations in this assay.

Sub-Category II

Nicotinonitrile (CASRN100-54-9)

Chinese hamster ovary (CHO) cells were exposed to nicotinonitrile concentrations up to
5000 |ig/mL with and without metabolic activation for six hours or up to 3000 |ag/mL without
activation for 24 and 48 hours. Positive and negative controls were tested concurrently;
however, the results were not provided. No cytotoxicity was observed. Nicotinonitrile did not
induce chromosomal aberrations with or without metabolic activation under these test conditions.
Nicotinonitrile did not induce chromosomal aberrations in this assay.

In vivo

Sub-Category I
Pyridine (CASRN 110-86-1)

(1) B6C3F1 mice (10 males/dose) were administered pyridine via intraperitoneal injection at
400, 500 and 600 mg/kg-bw. Positive and negative controls were tested concurrently; however,
the results were not provided. Two hours before sacrifice, the animals were administered
colchicine intraperitoneally. The mice were sacrificed at 17 or 36 hours. No induction of
aberrations was noted in bone marrow cells at either sampling time at any dose.

Pyridine did not induce chromosomal aberrations in this assay.

(2) B6C3F1 mice (5 males/dose) were administered pyridine via intraperitoneal injection at
31.25, 62.5, 125, 250 and 500 mg/kg-bw three times at 24-hour intervals. Positive and negative
controls were tested concurrently; however, the results were not provided. The animals were
sacrificed 24 hours after the third injection and blood smears were prepared from bone marrow
cells obtained from the femurs. The micronucleated polychromatic erythrocytes (MPCEs) per
1000 PCEs and the percent PCEs in the treated animals were not significantly different
(p>0.025) to the controls at any dose tested.

Pyridine did not increase micronuclei in this assay.

Sub-Category III
Piperidine (CASRN 110-89-4)

In a mouse micronucleus assay (OECD TG 474) NMRI mice of both sexes (6 mice/dose) were
treated with a single oral dose of piperidine at 40, 120 or 400 mg/kg-bw (maximum tolerated
dose). Five of the 18 animals died within 72 hours. No increase in polychromatic erythrocytes
was observed. (No other information provided). (http://www.bgchemie.de/files/95/ToxBew72-
L.pdf).

Piperidine did not increase micronuclei in this assay.

Genetic Toxicity - Other Effects
In vitro

Sub-Category I

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Pyridine (CASRN110-86-1)

(1) In a sister chromatid exchange (SCE) assay, Chinese hamster cells were exposed to pyridine
up to 0.005 M without metabolic activation. Positive controls were tested concurrently;
however, the results were not provided. The test substance did not induce SCE in this assay.
Pyridine did not induce chromosomal aberrations in this assay.

(2) In a sister chromatid exchange (SCE) assay, Chinese hamster ovary (CHO) cells were
exposed to pyridine up to 5020 |ag/m L with and without metabolic activation. Negative and
positive controls were tested concurrently and showed appropriate response. Cytotoxicity was
observed at 5020 jag/mL without metabolic activation. The test substance did not induce SCE in
this assay.

Pyridine did not induce chromosomal aberrations in this assay.

In vivo

Sub-Category I
Pyridine (CASRN 110-86-1)

In an unscheduled DNA synthesis (UDS) assay, B6C3F1 mice (4 males/dose) were administered
pyridine via gavage at 175, 350 or 700 mg/kg-bw. Mice were sacrificed 2 and 16 hours post
exposure. Primary hepatocytes were isolated, cultured and counted. Negative and positive
controls were tested; the negative control results were discussed. No treatment-related increase
in the UDS response was observed at any dose tested.

Pyridine did not induce unscheduled DNA synthesis in this assay.

Additional Information
Skin Irritation

The following information was retrieved from the TSCATS database accessible at:
(http://www.srcinc.com/what-we-do/databaseforms.aspx?id=384)

Sub-Category I
Pyridine (CASRN 110-86-1)

Six albino rabbits (sex not stated) were treated with 0.5 mL undiluted pyridine on intact and
abraded skin and observed at 24 and 72 hours.

Pyridine was corrosive to rabbit skin.

4-Picoline (CASRN 108-89-4)

(1) Six New Zealand white rabbits were exposed to 0.5 mL 4-picoline dermally on to the clipped
area of the skin under occluded condition for 4 hours. The skin was washed and observed at 24
and 48 hours. Corrosion was seen at the application site.

4-Picoline was corrosive to rabbit skin.

(2) Rabbits (strain not stated 1 male/2females) exposed to 0.2 mL 4-picoline dermally on to the
intact skin and evaluated after 1, 24 48, 72, 120 and 168 hours. The clinical observations ranged
from no changes through slight erythema and moderate edema ending with no erythema or

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

edema at 168 hours. A de-fatting effect was observed whereby flaking of the skin was observed
at 10-14 days.

4-Picoline was severely irritating to rabbit skin.

(3) New Zealand albino rabbits were exposed to 4-picoline dermally at dilutions of 8, 12.5, 25, or
50%. Except for 8% dilution, all doses were lethal to the rabbits. Additional rabbits were
exposed to 4-picoline at 0.5 or 1.0 g/kg-bw. All animals applied 1.0 g/kg-bw died. Animals
applied 0.5 g/kg survived. (No other information available)

3-Picoline (CASRN108-99-6)

(1) Six New Zealand white rabbits were exposed to 3-picoline dermally. Corrosion was
observed. (No other information available).

3-Picoline was corrosive to rabbit skin.

(2) When tested in guinea pigs, 3-picoline was moderately irritating to the skin. (No additional
information available).

3-Picoline was moderately irritating to guinea pig skin.

2-Picoline (CASRN 109-06-8)

(1) Six albino rabbits were exposed to 2-picoline dermally and observed at 4, 24 and 48 hours.
Moderate to severe erythema and corrosion were observed.

2-Picoline was corrosive to rabbit skin.

(2) Rabbits were exposed to undiluted 2-picoline six times on to the intact skin of the ear. Slight
hyperemia was observed during the first week which became moderate by week two. After the
sixth application, moderate burning was apparent. After 21 days, a slight scab remained.
2-Picoline was severely irritating to rabbit skin.

(3) Rabbits were exposed to undiluted 2-picoline dermally on to the intact and abraded skin.
Severe burning was accompanied by severe hyperemia and moderate edema after one
application. A severe scar with moderate scabbing remained after 21 days.

2-Picoline was severely irritating to rabbit skin.

(4) In a skin patch test, undiluted 2-picoline was applied to rabbit skin for 15 minutes, 5 minutes
or 1 minute. Moderate hyperemia was observed after two minutes; moderate burn after 15
minutes. The burn appeared to be severe with severe hyperemia one day later. A severe scab
remained in six days. After the five minute exposure, skin looked normal in a week. After the
one minute exposure, no irritation was observed the next day or a week later.

2-Picoline was severely irritating to rabbit skin.

Sub-Category III
Piperidine (CASRN 110-89-4)

(1) New Zealand White rabbits (2 male/4 females) were exposed to 0.5 mg Haccure 200 (a
mixture containing piperidine and 2-ethyl-4-methylimidazole) and Epon 828 dermally on to the

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

clipped skin under semi-occluded conditions 4 hours. After four hours, the gauze was removed
and the animals were scored for erythema and edema at 30-60 minutes and at 24, 48 and 72
hours, and days four and 14 following exposure. The study was terminated after 14 days. At 30-
60 minutes, there was slight to moderate edema in 5/6 rabbits. Moderate or severe erythema and
edema were observed on all rabbits from 24 hours to seven days. On day 14, except for one
rabbit, severe erythema with eschar formation and slight to severe edema were observed.
Piperidine was irritating to rabbit skin.

(2) New Zealand White rabbits (2 male/4 females) were exposed to 0.5 mL Haccure 200 (a
mixture containing piperidine and 2-ethyl-4-methylimidazole (4:6)) dermally on to the clipped
skin under semi-occluded condition for 4 hours. After four hours, the gauze was removed and
the animals were scored for erythema and edema at 30-60 minutes and at 24hours, and observed
for 14 days following exposure. At 30-60 minutes, there was slight to moderate edema in all
rabbits. Severe erythema and moderate to severe edema were observed on all rabbits at 24 hours.
Necrosis was observed at all test sites at both 30-60 minutes and 24 hours. The study was
terminated after 24 hours since the lesions were not considered reversible within the 14-day
study design.

Piperidine was corrosive to rabbit skin.

(3) Piperidine (0.5 mg) was tested in rabbits in a standard Draize test for 24 hours. Severe
dermal reaction was seen. (No other information available).

Piperidine was severely irritating to rabbit skin.

Eye Irritation

The following information was retrieved from the TSCATS database accessible at:
(http://www.srcinc.com/what-we-do/databaseforms.aspx?id=384)

Sub-Category I
Pyridine (CASRN110-86-1)

Six albino rabbits (sex not stated) were instilled with 0.1 mL undiluted pyridine into the eyes and

observed at 24, 48 and 72 hours.

Pyridine was severely irritating to rabbit eye.

4-Picoline (CASRN 108-89-4)

(1) New Zealand albino rabbits were instilled with 4-picoline in to the eyes. Both eyes were
observed for conjunctival, corneal or internal responses. One eye was washed within 30 seconds
while the other eye was unwashed. Severe conjunctival inflammation and swelling, severe
corneal injury and severe iritis were observed.

4-Picoline was severely irritating to rabbit eye.

(2) Albino rabbits (3 male and females) were instilled with undiluted 4-picoline (0.1 mL) in the
right eye and observed for seven days. The eyes were rinsed with warm isotonic saline solution
after either a 24 hour exposure or 15 minute exposure. The left eye served as the control. At 24
hours, opacity of the eye was observed with accompanying discharge, at both exposures. The
test substance was considered a severe eye irritant at both exposure times.

4-Picoline was severely irritating to rabbit eye.

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

3-Picoline (CASRN108-99-6)

When tested in rabbit eye, 3-picoline was a severe eye irritant.

3-Picoline was severely irritating to rabbit eye.

2-Picoline (CASRN 109-06-8)

Rabbit was instilled with undiluted 2-picoline with and without washing. There was slight pain
upon direct contact followed by severe conjunctival and corneal injury resulting in permanent
impairment of vision and possibly total loss of sight. Corneal injury was apparent immediately
after contact.

2-Picoline was severely irritating to rabbit eye.

Sub-Category III
Piperidine (CASRN 110-89-4)

Rabbits were instilled with 250 |Jg piperidine in a standard Draize test for 24 hours. The
reaction was severe. (No other information provided).

Piperidine was severely irritating in rabbit eye.

Sensitization

The following information was retrieved from the TSCATS database accessible at:
(http://www.srcinc.com/what-we-do/databaseforms.aspx?id=384)

Sub-Category I
Pyridine (CASRN 110-86-1)

Pyridine was evaluated for dermal sensitization in guinea pigs and was determined not to be a
sensitizer. No other information is available.

Pyridine is not a skin sensitizer.

Sub-Category III
Piperidine (CASRN 110-89-4)

Haccure 200 is a mixture containing (piperidine and 2-ethyl-4-methylimidazole, 4:6).

In a contact dermal sensitization test, ten female guinea pigs were applied 0.5 mL Haccure 200
(piperidine) as a 30% (v/v) suspension in propylene glycol to a 4 x 4 cm patch and attached to
hair clipped skin. A concentration of 30% was chosen due to severe dermal reactions at higher
concentrations. The induction applications were made 3 times each week until all nine induction
applications had been made. Animals were challenged two weeks after the last induction with
0.5 mL test substance. Sites of application were evaluated for erythema, edema and other lesions
approximately 24 and 48 hours after the test substance application. The positive control behaved
as expected. The test substance was considered a contact dermal sensitizer.

Piperidine is a skin sensitizer.

Carcinogenicity

Sub-Category I
Pyridine (CASRN 110-86-1)

(1) In a two-year NTP study, B6C3F1 mice (50/sex/concentration) were exposed to pyridine in
drinking water at 0, 250, 500 or 1000 ppm (males; 0, 35, 65, 110 mg/kg-bw/day or 0, 125, 250 or

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

500 ppm (females; 0, 15, 35 or 70 mg/kg-bw/day). Hepatocellular neoplasm, including
hepatoblastomas in exposed male and female mice were treatment-related. http://ntp-
apps.niehs.nih.gov/ntp tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=l 10-86-1
Pyridine increased the incidence of tumors in this study.

(2)	In a two-year NTP study, Fischer 344 rats (50/sex/concentration) were exposed to pyridine in
drinking water at 0, 100, 200 or 400 ppm (0 and approximately 7, 14 or 33 mg/kg-bw/day).
Incidences of renal tubular adenoma or carcinoma were observed in males and were considered
treatment-related. Similarly, incidences of mononuclear cell leukemia in females were also
considered treatment-related.

http://ntp-

apps.niehs.nih.gov/ntp tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=l 10-86-1
Pyridine increased the incidence of tumors in this study.

(3)	In a two-year NTP study, male Wistar rats (50/sex/concentration) were exposed to pyridine in
drinking water at 0, 100, 200 or 400 ppm (0 and approximately 8, 17 or 36 mg/kg-bw/day).
Survival of rats exposed to 200 or 400 ppm was significantly less than that of controls.

Incidences of testicular adenoma were considered treatment-related.

http://ntp-

apps.niehs.nih.gov/ntp tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=l 10-86-1
Pyridine increased the incidence of tumors in this study.

Sub-Category III
Piperidine (CASRN110-89-4)

In a 50-week study, Sprague-Dawley rats (15/sex/concentration) were exposed to piperidine in
drinking water at 0 or 0.09% (approximately 50 mg/kg-bw/day) with and without 0.2% sodium
nitrite 5 days/week. There was no significant increase in the tumor incidence in rats chronically
exposed to 0.09% piperidine with or without sodium nitrite as compared to control rats receiving
0.2%) sodium nitrite in drinking water.

Piperidine did not increase the incidence of tumors in this study.

Other

Sub-Category I
Pyridine (CASRN 110-86-1)

Sprague-Dawley rats (5 males/dose) were administered 1.25 mmol pyridine intraperitoneally
daily for five days. The animals were sacrificed 18 hours after the last injection. Serum sorbitol
dehydrogenase (SDH), blood urea nitrogen (BUN), serum creatinine and />nitrophenol
hydroxylase were measured. Pyridine was hepatotoxic as indicated by increased SDH activity.
An increase in /;-nitrophenol hydroxylase activity indicated that pyridine induced the metabolism
of />nitrophenol.

Pyridine is potentially hepatotoxic.

32

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Conclusion:

Sub-Category I: The acute toxicity of sub-category I is low via the oral (rats), high via the
dermal (rabbits) and moderate via the inhalation (rats) routes of exposure. The alkyl pyridines
are corrosive to rabbit skin and severely irritating to rabbit eye. CASRN 110-86-1 is not a skin
sensitizer in guinea pigs. Oral repeated-dose studies with CASRN 110-86-1 in rats showed
systemic toxicity ranging from changes in body weights to histopathological changes in the liver
at 33 mg/kg-bw/day; the NOAEL was 14 mg/kg-bw/day. In mice, repeated oral exposures
showed effects on body weight gain and liver at 200 mg/kg-bw/day; the NOAEL for systemic
toxicity was 100 mg/kg-bw/day. Repeated inhalation exposures of male rats to CASRN
108-99-6 showed no effects at the highest concentration tested; the NOAEC for systemic toxicity
was 1.10 mg/L. Repeated inhalation exposures of rats to CASRN 109-06-8 showed no effects at
the highest concentration tested; the NOAEC for systemic toxicity was 0.38 mg/L. Effects were
observed on body weights and liver; the NOAEC for systemic toxicity was not established. No
specific reproductive toxicity studies were available but effects on the male reproductive system
were observed after repeated oral exposures to CASRN 110-86-1 in mice and rats. No
developmental toxicity studies were available. Sub-category I did not induce gene mutations in
vitro. CASRN 110-86-1 did not induce chromosomal aberrations in vitro or in vivo. In two-year
bioassays in rats and mice exposed via drinking water, CASRN 110-86-1 increased the incidence
of tumors.

The reproductive and developmental toxicity endpoints remain as data gaps under the HPV
Challenge Program.

Sub-Category II: The acute toxicity of sub-category II is low via the oral (rats) and dermal
(rabbits) routes of exposure. Repeated oral exposures with CASRN 100-54-9 in rats showed
histopathological changes in the liver at 30 mg/kg-bw/day; the NOAEL for systemic toxicity was
5 mg/kg-bw/day. At higher doses, there was necrosis of spermatocytes and spermatids. No
specific reproductive toxicity studies were available but effects on the male reproductive system
were observed after repeated oral exposures to CASRN 100-54-9 in rats. No developmental
toxicity studies were available. CASRN 100-54-9 did not induce gene mutations or
chromosomal aberrations in vitro.

The reproductive and developmental toxicity endpoints remain as data gaps under the HPV
Challenge Program.

Sub-Category III: The acute oral toxicity of CASRN 110-89-4 is moderate in rats and low in
mice. Acute dermal toxicity in rabbits and inhalation toxicity in rats is moderate. CASRN
110-89-4 is corrosive to rabbit skin, severely irritating to rabbit eye and a skin sensitizer in
guinea pigs. After repeated inhalation exposures, no adverse effects were observed in rats at the
highest dose tested; the NOAEC for systemic toxicity was 0.348 mg/L. No data were available
for the reproductive toxicity endpoint. In a prenatal developmental toxicity study in rats via the
inhalation route, dams showed decreased weight gains at 0.015 mg/L; the NOAEC for maternal
toxicity was 0.003 mg/L. Fetal body weights were decreased at 0.003 mg/L. The NOAEC for
developmental toxicity was not established. CASRN 110-89-4 did not induce gene mutations
in vitro and did not induce micronuclei in vivo. No data were available for the chromosomal
aberrations endpoint. In a two-year bioassay in rats exposed via drinking water, CASRN

-------
U.S. Environmental Protection Agency	September, 2009

Hazard Characterization Document

110-89-4 did not increase the incidence tumors.

The reproductive toxicity endpoint remains a data gap under the HPV Challenge Program.

34

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

TablcS. Summary of Human Health Data

End points

Sub-Category I

Sub-Category II

Sub-Category III

Pyridine

(CASRN
110-86-1)

4-Picoline

(CASRN
108-89-4)

3-Picoline

(CASRN
108-99-6)

2-Picoline

(CASRN
109-06-8)

Pyridine, alky 1
derivatives
(CASRN
68391-11 -7)

Nicotinonitrile

(CASRN
100-54-9)

Picolinonitrile

(CASRN
100-70-9)

Piperidine

(CASRN
110-89-4)

Acute Oral
Toxicity

LDS0 (mg/kg-bw)

800-1600

700 to 841

630 to 710

810 to >950

2500

633 to 1455

No Data
633-1455
(RA)

337 to 740 (rats)
536 to 633 (mice)

Acute Dermal Toxicity
LDS0 (mg/kg-bw)

1000 to 2000

79.4 to 200

126 to 1000

200 to 500

>2.0
(mL/kg-bw)

2000 to 4000



276

Acute Inhalation Toxicity
LC50 (mg/L)

<12

3.8 to 9.2

5.0 to 11.8

7.6 to 13.2







4.8

Repeated-Dose Toxicity
NOAEC/ LOAEC
Inhalation (mg/L)

NOAEC = NE
LOAEC = 0.02

_«

NOAEC = 1.1

(highest
concentration
tested)

NOAEC- 0.38

(highest
concentration
tested)







NOAEC ~ 0.348
(highest concentration
tested)

Repeated-Dose Toxicity
NOAEL/ LOAEL
Oral (mg/kg-bw/day)

(rat)
NOAEL = 8
LOAEL = 17

(mice)
NOAEL = 100
LOAEL = 200

No data

(rat)
NOAEL = 8
LOAEL = 17
(RA)

(mice)
NOAEL = 100
LOAEL = 200
(RA)

No data

(rat)
NOAEL = 8
LOAEL = 17
(RA)

(mice)
NOAEL = 100
LOAEL = 200
(RA)

No data

(rat)
NOAEL = 8
LOAEL = 17
(RA)

(mice)
NOAEL = 100
LOAEL = 200
(RA)

No data

(rat)
NOAEL = 8
LOAEL = 17
(RA)

(mice)
NOAEL = 100
LOAEL = 200
(RA)

(rat)
NOAEL = 5
LOAEL = 30

No Data

(rat)
NOAEL = 5
LOAEL = 30
(RA)

_«

Reproductive Toxicity
NOAEL/ LOAEL
Oral (mg/kg-bw/day)

Data Gap

Data from repeated-dose study indicate effects on sperm motility in mice.
Data from two-year study in rats show increased incidence of testicular adenoma.

Data Gap

Data from repeated-dose study
indicate effects on spermatocytes and
spermatids in rats.

Data Gap

Developmental Toxicity
NOAEC/ LOAEC
Inhalation (mg/L)

Maternal Toxicity

Developmental Toxicity

Data Gap

Data Gap

NOAEC = 0.003
LOAEC = 0.015

NOAEC = NE
LOAEC = 0.003

35

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

TablcS. Summary of Human Health Data

End points

Sub-Category I

Sub-Category II

Sub-Category III

Pyridine

(CASRN
110-86-1)

4-Picoline

(CASRN
108-89-4)

3-Picoline

(CASRN
108-99-6)

2-Picoline

(CASRN
109-06-8)

Pyridine, alky 1
derivatives
(CASRN
68391-11 -7)

Nicotinonitrile

(CASRN
100-54-9)

Picolinonitrile

(CASRN
100-70-9)

Piperidine

(CASRN
110-89-4)

Genetic Toxicity - Gene

Mutation

In vitro

Negative

Negative

Negative

Negative

No Data
Negative
(RA)

Negative

No Data
Negative
(RA)

Negative

Genetic Toxicity -
Chromosomal
Aberrations
In vitro

Negative

No Data
Negative
(RA)

No Data
Negative
(RA)

No Data
Negative
(RA)

No Data
Negative
(RA)

Negative

No Data
Negative
(RA)

_«

Genetic Toxicity -
Chromosomal
Aberrations
In vivo

Negative













Negative

Genetic Toxicity -
Other Effects
In vitro



_«













Unscheduled DNA
Synthesis

Mouse Lymphoma
SCE

Negative

Negative
Negative















Skin Irritation

Corrosive

Corrosive

Corrosive

Corrosive







Corrosive

Eye Irritation

Severe

Severe

Severe

Severe







Severe

Skin Sensitization

Negative













Positive

Carcinogenicity

Positive













Negative

Measured data in bold text; (RA) = read across; -** endpoint not addressed for this chemical; NE = not established; m = male; f = female

36

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

4 Hazards to the Environment

A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 9. The
table also indicates where data for tested category members are read across (RA) to untested
members of the category.

Acute Toxicity to Fish

Sub-Category I
Pyridine (CASRN110-86-1)

Fathead minnow (Pimephalespromelas) were exposed to pyridine (concentrations not stated)
under flow-through test conditions for 96 hours with analytical monitoring.

96-h LCso = 99 mg/L

4-Picoline (CASRN 108-89-4)

Sheepshead minnow (Cyprinodon variegatus) were exposed to 4-picoline (concentrations not
stated) under flow-through test conditions for 96 hours with analytical monitoring.

96-h LCso = 400 mg/L

3-Picoline (CASRN 108-99-6)

Zebra fish (Brachydanio rerio) were exposed to 3-picoline at nominal concentrations of 0, 100,
180, 320, 560 and 1000 mg/L under static-renewal conditions for 96 hours with no analytical
monitoring. Mortality was observed at concentrations greater than 560 mg/L.

96-h LCso > 560 mg/L

2-Picoline (CASRN 109-06-8)

Fathead minnow (Pimephales promelas) were exposed to 2-picoline at measured concentrations
of <15, 230, 333, 475, 718 or 1119 mg/L under flow-through conditions for 96 hours with
analytical monitoring. Mortality was 100% at 1119 mg/L and occurred within 3 hours following
exposure.

96-h LCso = 897 mg/L

Pyridine, alkyl derivs (CASRN 68391-11-7)

Rainbow trout (Oncorhynchus mykiss) were exposed to pyridine, alkyl derivative at nominal
concentrations of 0, 6.25, 12.5, 25, 50 and 100 mg/L under static conditions for 96 hours with no
analytical monitoring. Mortality was 100% at 100 mg/L and 80% at 50 mg/L.

96-h LCso = 40 mg/L

Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

Data for acute toxicity to fish were not provided for nicotinonitrile. A 96-hour EC50 for fish,
estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute toxicity of nicotinonitrile.
96-h ECso= 2264 mg/L (ECOSAR v. 1.00a)

37

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Picolinonitrile (CASRN100-70-9)

Fathead minnow (Pimephalespromelas) were exposed to picolinonitrile (concentrations not
stated) under flow-through conditions for 96 hours with analytical monitoring.

96-h LCso = 726 mg/L

Sub-Category III
Piperidine (CASRN 110-89-4)

A standard acute toxicity test for fish was not provided for piperidine. A 96-hour EC50 for fish,
estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute toxicity of piperidine.
96-h EC50= 46 mg/L (ECOSAR v. 1.00a)

Acute Toxicity to Aquatic Invertebrates

Sub-Category I
Pyridine (CASRN 110-86-1)

Daphnia magna, pulex, and cucullata were exposed (concentrations not stated) to pyridine under
static conditions for 48 hours with no analytical monitoring.

48-h ECS0= 1130-1755, 575 and 2470 mg/L for magna, pulex and cucullata, respectively.
4-Picoline (CASRN 108-89-4)

A standard acute toxicity test for invertebrates was not provided for 4-picoline. A 48-hour EC50
for invertebrates, estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute toxicity
of 4-picoline.

48-h EC50= 137 mg/L (ECOSAR v. 1.00a)

3-Picoline (CASRN 108-99-6)

Water flea (Daphnia magna) were exposed to 3-picoline at nominal concentrations of 0, 100,
180, 320, 560 or 1000 mg/L under static conditions for 48 hours with no analytical monitoring.
48-h EC5o=320 mg/L

2-Picoline (CASRN 109-06-8)

A standard acute toxicity test for invertebrates was not provided for 2-picoline. A 48-hour EC50
for invertebrates, estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute toxicity
of 2-picoline.

48-h EC5o= 137 mg/L (ECOSAR v. 1.00a)

Pyridine, alkyl derivs (CASRN 68391-11-7)

Waterflea (Daphnia magna) were exposed to pyridine alkyl derivatives at nominal
concentrations of 0, 31.3, 62.5, 125, 250 and 500 mg/L under static conditions for 48 hours with
no analytical monitoring. Mortality was 100% at 250 and 500 mg/L.

48-h EC50 = 69 mg/L

Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

38

-------
U.S. Environmental Protection Agency	September, 2009

Hazard Characterization Document

A standard acute toxicity test for invertebrates was not provided for nicotinonitrile. A 48-hour
EC50 for invertebrates, estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute
toxicity of nicotinonitrile.

48-h EC50= 1000 mg/L (ECOSAR v. 1.00a)

Picolinonitrile (CASRN100-70-9)

A standard acute toxicity test for invertebrates was not provided for picolinonitrile. A 48-hour
EC50 for invertebrates, estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute
toxicity of picolinonitrile.

48-h EC50= 1000 mg/L (ECOSAR v. 1.00a)

Sub-Category III
Piperidine (CASRN 110-89-4)

A standard acute toxicity test for invertebrates was not provided for piperidine. A 48-hour EC50
for invertebrates, estimated by ECOSAR (v. 1.00a), was provided to evaluate the acute toxicity
of piperidine.

48-h EC5o= 4 mg/L (ECOSAR v. 1.00a)

Toxicity to Aquatic Plants

Sub-Category I
Pyridine (CASRN 110-86-1)

A standard toxicity test for aquatic plants was not provided for pyridine. A 96-hour EC50 for
aquatic plants, estimated by ECOSAR (v. 1.00a), was provided to evaluate the toxicity to aquatic
plants of pyridine.

96-h EC50= 92 mg/L (ECOSAR v. 1.00a)

4-Picoline (CASRN 108-89-4)

A standard toxicity test for aquatic plants was not provided for 4-picoline. A 96-hour EC50 for
aquatic plants, estimated by ECOSAR (v. 1.00a), was provided to evaluate the toxicity to aquatic
plants of 4-picoline.

96-h EC5o= 49 mg/L (ECOSAR v. 1.00a)

3-Picoline (CASRN 108-99-6)

Green algae (Pseudokirchneriella subcapitata) were exposed to 3-picoline at nominal
concentrations 0, 10, 32, 100, 320 or 1000 mg/L for 72 hours with no analytical monitoring. The
reduction in the average specific growth rate began at 10 mg/L and continued till growth
completely stopped at 1000 mg/L.

72-h EC50 (growth rate) = 320 mg/L

2-Picoline (CASRN 109-06-8)

A standard toxicity test for aquatic plants was not provided for 2-picoline. A 96-hour EC50 for
aquatic plants, estimated by ECOSAR (v. 1.00a), was provided to evaluate the toxicity to aquatic
plants of 2-picoline.

96-h EC5o= 49 mg/L (ECOSAR v. 1.00a)

39

-------
U.S. Environmental Protection Agency September, 2009

Hazard Characterization Document

Pyridine, alkyl derivatives (CASRN 68391-11-7)

A standard toxicity test for aquatic plants was not provided
96-hour EC50 for aquatic plants, estimated by ECOSAR (v.
toxicity to aquatic plants from pyridine, alkyl derivatives.

96-h EC5o= 14.2 mg/L (ECOSAR v. 1.00a)

Sub-Category II

Nicotinonitrile (CASRN 100-54-9)

A standard toxicity test for aquatic plants was not provided for nicotinonitrile.
for aquatic plants, estimated by ECOSAR (v. 1.00a), was provided to evaluate
aquatic plants of nicotinonitrile.

96-h EC50= 232 mg/L (ECOSAR v. 1.00a)

Picolinonitrile (CASRN 100-70-9)

A standard toxicity test for aquatic plants was not provided for picolinonitrile.
for aquatic plants, estimated by ECOSAR (v. 1.00a), was provided to evaluate
aquatic plants of picolinonitrile.

96-h EC50= 232 mg/L (ECOSAR v 1.00a)

Sub-Category III
Piperidine (CASRN 110-89-4)

A standard toxicity test for aquatic plants was not provided for piperidine. A 96-hour EC50 for
aquatic plants, estimated by ECOSAR (v. 1.00a), was provided to evaluate the toxicity to aquatic
plants of piperidine.

96-h EC50 = 1.2 mg/L (ECOSAR v. 1.00a)

Conclusion:

Sub-Category I: The acute hazard to fish is based on the toxicity values for CASRNs 108-89-4,
108-99-6, 109-06-8, 110-86-1 and 68391-11-7 ranging from 40 to 897 mg/L. The acute hazard
to aquatic invertebrates is based on the toxicity values for CASRNs 108-99-6, 110-86-1 and
68391-11-7 ranging from 69 to 2470 mg/L. The acute hazard to aquatic plants is based on the
toxicity value for CASRN 108-99-6 of 320 mg/L.

Sub-Category II: The acute hazard to fish is based on the toxicity value for CASRN 100-70-9 of
726 mg/L. The acute hazard to aquatic invertebrates is based on the estimated toxicity values for
CASRNs 100-54-9 and 100-70-9 of 1000 mg/L. The acute hazard to aquatic plants is based on
the estimated toxicity values for CASRNs 100-54-9 and 100-70-9 of 232 mg/L.

The acute toxicity to aquatic invertebrates and aquatic plants remain as data gaps under the HPV
Challenge Program.

Sub-Category III: The acute hazard to fish is based on the estimated toxicity value for CASRN
110-89-4 of 46 mg/L. The acute hazard to aquatic invertebrates is based on the estimated
toxicity value for CASRN 110-89-4 of 4 mg/L. The acute hazard to aquatic plants is based on
the estimated toxicity values for CASRN 110-89-4 of 1.2 mg/L.

for pyridine, alkyl derivatives. A
1.00a), was provided to evaluate the

A 96-hour EC50
the toxicity to

-------
U.S. Environmental Protection Agency	September, 2009

Hazard Characterization Document

The acute toxicity to fish, aquatic invertebrates and aquatic plants remain as data gaps under the
HPV Challenge Program.

41

-------
U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2009

Table 9. Summary of Environmental Effects - Aquatic Toxicity Data

Endpoints

Sub-Catcgorv I

Sub-Catcgorv II

Sub-Catcgorv III

Pyridine

(CASRN
110-86-1)

4-Picoline

(CASRN
108-89-4)

3-Picoline

(CASRN
108-99-6)

2-Picoline

(CASRN
109-06-8)

Pyridine, alkyl
derivatives
(CASRN
68391-11-7)

Nicotinonitrile

(CASRN
100-54-9)

Picolinonitrile

(CASRN
100-70-9)

Piperidine

(CASRN
110-89-4)

Fish

96-h LCS0
(mg/L)

99

400

>560

897

40

No Data
726
(RA)

726

Data Gap
46 (e)

Aquatic
Invertebrates
48-h ECS0
(mg/L)

575-2470

No Data
320
(RA)

320

No Data
320
(RA)

69

Data Gap
1000 (e)

Data Gap
1000 (e)

Data Gap
4(e)

Aquatic Plants
72-h ECS0
(mg/L)

No Data
320
(RA)

No Data
320
(RA)

320

No Data
320
(RA)

No Data
320
(RA)

Data Gap
232 (96-h)
(e)

Data Gap
232 (96-h)
(e)

Data Gap
1.2 (96-h)
(e)

Measured data (i.e. derived from testing) are in bold; (e) = estimated data (i.e., derived from modeling); (RA) = read across

42

-------