iPs	United States
Environmental Protection
m»Agency
EPA/690/R-05/007F
Final
3-15-2005
Provisional Peer Reviewed Toxicity Values for
Anilinobenzothiazole
(CASRN 1843-21-6)
Derivation of Subchronic and Chronic Oral RfDs
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms
bw - body weight
cc - cubic centimeters
CD - Caesarean Delivered
CERCLA - Comprehensive Environmental Response, Compensation, and Liability Act of 1980
CNS - central nervous system
cu.m - cubic meter
DWEL - Drinking Water Equivalent Level
FEL - frank-effect level
FIFRA - Federal Insecticide, Fungicide, and Rodenticide Act
g - grams
GI - gastrointestinal
HEC - human equivalent concentration
Hgb - hemoglobin
i.m. - intramuscular
i.p. - intraperitoneal
i.v. - intravenous
IRIS - Integrated Risk Information System
IUR - Inhalation Unit Risk
kg - kilogram
L - liter
LEL - lowest-effect level
LOAEL - lowest-observed-adverse-efifect level
LOAEL(ADJ) - LOAEL adjusted to continuous exposure duration
LOAEL(HEC) - LOAEL adjusted for dosimetric differences across species to a human
m - meter
MCL - maximum contaminant level
MCLG - maximum contaminant level goal
MF - modifying factor
mg - milligram
mg/kg - milligrams per kilogram
mg/L - milligrams per liter
MRL - minimal risk level
MTD - maximum tolerated dose
1

-------
MTL - median threshold limit
NAAQS - National Ambient Air Quality Standards
NOAEL - no-observed-adverse-effect level
NOAEL(ADJ) - NOAEL adjusted to continuous exposure duration
NOAEL(HEC) - NOAEL adjusted for dosimetric differences across species to a human
NOEL - no-observed-effect level
OSF - Oral Slope Factor
p-RfD - provisional Oral Reference Dose
p-RfC - provisional Inhalation Reference Concentration
p-OSF - provisional Oral Slope Factor
p-IUR - provisional Inhalation Unit Risk
PBPK - physiologically based pharmacokinetic
ppb - parts per billion
ppm - parts per million
PPRTV - Provisional Peer Reviewed Toxicity Value
RBC - red blood cell(s)
RCRA - Resource Conservation and Recovery Act
RGDR - Regional deposited dose ratio (for the indicated lung region)
REL - relative exposure level
RGDR - Regional gas dose ratio (for the indicated lung region)
RfD - Oral Reference Dose
RfC - Inhalation Reference Concentration
s.c. - subcutaneous
SCE - sister chromatid exchange
SDWA - Safe Drinking Water Act
sq.cm. - square centimeters
TSCA - Toxic Substances Control Act
UF - uncertainty factor
ug - microgram
umol - micromoles
VOC - volatile organic compound
11

-------
03-15-05
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
ANILINOBENZOTHIAZOLE (CASRN 1843-21-6)
Derivation of Subchronic and Chronic Oral RfDs
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
1

-------
03-15-05
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
A subchronic or chronic RfD for anilinobenzothiazole is not available on IRIS (U.S.
EPA, 2002a), the HEAST (U.S. EPA, 1997), or the Drinking Water Standards and Health
Advisories list (U.S. EPA, 2002b). No relevant documents were located in the CARA list (U.S.
EPA, 1991, 1994). Neither ATSDR (2002), NTP (2002), IARC (2002), nor WHO (2002) have
produced documents regarding anilinobenzothiazole. Literature searches of the following
databases were conducted from 1965 through July 2002 in order to locate relevant studies:
TOXLINE, CANCERLIT, MEDLINE, CCRIS, GENETOX, HSDB, DART/ETICBACK,
EMIC/EMICBACK, RTECS and TSCATS. An updated literature search was conducted through
April 2004 and no relevant information was found.
2

-------
03-15-05
REVIEW OF THE PERTINENT DATA
Human Studies
No data regarding the toxicity of anilinobenzothiazole to humans following chronic or
subchronic oral exposure were located.
Animal Studies
No data regarding the toxicity of anilinobenzothiazole to animals following chronic or
subchronic oral exposure were located.
FEASIBILITY OF DERIVING A PROVISIONAL SUBCHRONIC OR CHRONIC
RfD FOR ANILINOBENZOTHIAZOLE
The lack of chronic or subchronic oral toxicity data for humans or animals precludes
derivation of a subchronic or chronic RfD for anilinobenzothiazole. It was considered that
systemic toxicity values might be obtained by analogy to 2-mercaptobenzothiazole (MBT), which
has toxicity and carcinogenicity information. However, the pharmacokinetic data on MBT
(Colucci and Buyske, 1965; El Dareer et al., 1989; Larsen et al., 1988; Nagamatsu et al., 1979)
do not suggest that biotransformation to anilinobenzothiazole would occur, and no obvious
pathways for biotransformation of anilinobenzothiazole to MBT were identified. In addition,
there is some evidence that the sulfhydryl group is involved in MBT carcinogenicity (NTP, 1988)
and other aspects of MBT toxicity (Feinman, 1987).
REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html
Colucci, D.F. and D.A. Buyske. 1965. The biotransformation of a sulfonamide to a mercaptan
and to mercapturic acid and glucuronide conjugates. Biochem. Pharmacol. 14: 457-466.
El Dareer, S.M., J.R. Kalin, K.F. Tillery et al. 1989. Disposition of 2-mercaptobenzothiazole
and 2-mercaptobenzothiazole disulfide in rats dosed intravenously, orally and topically and in
guinea-pigs dosed topically. J. Toxicol. Environ. Health. 27(1): 65-84.
Feinman, S.E. 1987. Sensitivity to rubber chemicals. J. Toxicol.-Cut. Ocular Toxicol. 6(2):
117-153.
3

-------
03-15-05
I ARC (International Agency for Research on Cancer). 2002. IARC Agents and Summary
Evaluations. Online. http://193.51.164.il/cgi/iHound/Chem/iH Chem Frames.html
Larsen, G.L., J.E. Bakke, V.J. Feil and J.K. Huwe. 1988. In vitro metabolism of the methylthio
group of 2-methylthiobenzothiazole by rat liver. Xenobiotica. 18(3): 313-322.
Nagamatsu, K., Y. Kido, G. Urakubo et al. 1979. Absorption, distribution, excretion and
metabolism of 2-mercaptobenzothiazole in guinea pig. Eisei Kagaku. 25: 59-65. (Cited in NTP,
1988)
NTP (National Toxicology Program). 1988. Technical Report on the Toxicology and
Carcinogenesis Studies of 2-Mercaptobenzothiazole (CAS No. 149-30-4) in F344/N Rats and
B6C3F1 Mice. National Toxicology Program, Research Triangle Park, NC. NTP TR 332. NTIS
PB 88245154. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/ALL SRCH/iH ALL SRCH Frames.html
NTP (National Toxicology Program). 2002. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC. July.
EPA/540/R-97/036. NTIS 97-921199.
U.S. EPA. 2002a. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/
U.S. EPA. 2002b. 2002 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-02-038. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf
WHO (World Health Organization). 2002. Online Catalogs for the Environmental Criteria
Series. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
4

-------
03-15-05
Provisional Peer Reviewed Toxicity Values for
Anilinobenzothiazole
(CASRN 1843-21-6)
Derivation of Subchronic and Chronic Inhalation RfCs
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms
bw - body weight
cc - cubic centimeters
CD - Caesarean Delivered
CERCLA - Comprehensive Environmental Response, Compensation, and Liability Act of 1980
CNS - central nervous system
cu.m - cubic meter
DWEL - Drinking Water Equivalent Level
FEL - frank-effect level
FIFRA - Federal Insecticide, Fungicide, and Rodenticide Act
g - grams
GI - gastrointestinal
HEC - human equivalent concentration
Hgb - hemoglobin
i.m. - intramuscular
i.p. - intraperitoneal
i.v. - intravenous
IRIS - Integrated Risk Information System
IUR - Inhalation Unit Risk
kg - kilogram
L - liter
LEL - lowest-effect level
LOAEL - lowest-observed-adverse-efifect level
LOAEL(ADJ) - LOAEL adjusted to continuous exposure duration
LOAEL(HEC) - LOAEL adjusted for dosimetric differences across species to a human
m - meter
MCL - maximum contaminant level
MCLG - maximum contaminant level goal
MF - modifying factor
mg - milligram
mg/kg - milligrams per kilogram
mg/L - milligrams per liter
MRL - minimal risk level
MTD - maximum tolerated dose
1

-------
MTL - median threshold limit
NAAQS - National Ambient Air Quality Standards
NOAEL - no-observed-adverse-effect level
NOAEL(ADJ) - NOAEL adjusted to continuous exposure duration
NOAEL(HEC) - NOAEL adjusted for dosimetric differences across species to a human
NOEL - no-observed-effect level
OSF - Oral Slope Factor
p-RfD - provisional Oral Reference Dose
p-RfC - provisional Inhalation Reference Concentration
p-OSF - provisional Oral Slope Factor
p-IUR - provisional Inhalation Unit Risk
PBPK - physiologically based pharmacokinetic
ppb - parts per billion
ppm - parts per million
PPRTV - Provisional Peer Reviewed Toxicity Value
RBC - red blood cell(s)
RCRA - Resource Conservation and Recovery Act
RGDR - Regional deposited dose ratio (for the indicated lung region)
REL - relative exposure level
RGDR - Regional gas dose ratio (for the indicated lung region)
RfD - Oral Reference Dose
RfC - Inhalation Reference Concentration
s.c. - subcutaneous
SCE - sister chromatid exchange
SDWA - Safe Drinking Water Act
sq.cm. - square centimeters
TSCA - Toxic Substances Control Act
UF - uncertainty factor
ug - microgram
umol - micromoles
VOC - volatile organic compound
11

-------
03-15-05
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
ANILINOBENZOTHIAZOLE (CASRN 1843-21-6)
Derivation of Subchronic and Chronic Inhalation RfCs
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
1

-------
03-15-05
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
A subchronic or chronic RfC for anilinobenzothiazole is not available on IRIS (U.S. EPA,
2002) or in the HEAST (U.S. EPA, 1997). No relevant documents were located in the CARA
list (U.S. EPA, 1991, 1994). ACGIH (2001), NIOSH (2002) and OSHA (2002) have not
recommended occupational exposure limits for anilinobenzothiazole. ATSDR (2002), NTP
(2002), IARC (2002), and WHO (2002) have not produced documents for this chemical.
Literature searches of the following databases were conducted from 1965 through July 2002 in
order to locate relevant studies: TOXLINE, CANCERLIT, MEDLINE, CCRIS, GENETOX,
HSDB, DART/ETICBACK, EMIC/EMICBACK, RTECS and TSCATS. An updated literature
search was conducted through April 2004 and no relevant information was found.
2

-------
03-15-05
REVIEW OF THE PERTINENT DATA
Human Studies
No data regarding the toxicity of anilinobenzothiazole to humans following chronic or
subchronic inhalation exposure were located.
Animal Studies
No data regarding the toxicity of anilinobenzothiazole to animals following chronic or
subchronic inhalation exposure were located.
FEASIBILITY OF DERIVING A PROVISIONAL SUBCHRONIC OR CHRONIC
RfC FOR ANILINOBENZOTHIAZOLE
The lack of chronic or subchronic inhalation data for humans or animals precludes
derivation of a subchronic or chronic RfC for anilinobenzothiazole. It was considered that
systemic toxicity values might be obtained by analogy to 2-mercaptobenzothiazole (MBT), which
has toxicity and carcinogenicity information. However, the pharmacokinetic data on MBT
(Colucci and Buyske, 1965; El Dareer et al., 1989; Larsen et al., 1988; Nagamatsu et al., 1979)
do not suggest that biotransformation to anilinobenzothiazole would occur, and no obvious
pathways for biotransformation of anilinobenzothiazole to MBT were identified. In addition,
there is some evidence that the sulfhydryl group is involved in MBT carcinogenicity (NTP, 1988)
and other aspects of MBT toxicity (Feinman, 1987).
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2001. 2001 Threshold
Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices.
Cincinnati, OH.
ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html
Colucci, D.F. and D.A. Buyske. 1965. The biotransformation of a sulfonamide to a mercaptan
and to mercapturic acid and glucuronide conjugates. Biochem. Pharmacol. 14: 457-466.
3

-------
03-15-05
El Dareer, S.M., J.R. Kalin, K.F. Tillery et al. 1989. Disposition of 2-mercaptobenzothiazole
and 2-mercaptobenzothiazole disulfide in rats dosed intravenously, orally and topically and in
guinea-pigs dosed topically. J. Toxicol. Environ. Health. 27(1): 65-84.
Feinman, S.E. 1987. Sensitivity to rubber chemicals. J. Toxicol.-Cut. Ocular Toxicol. 6(2):
117-153.
I ARC (International Agency for Research on Cancer). 2002. IARC Agents and Summary
Evaluations. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
Larsen, G.L., J.E. Bakke, V.J. Feil and J.K. Huwe. 1988. In vitro metabolism of the methylthio
group of 2-methylthiobenzothiazole by rat liver. Xenobiotica. 18(3): 313-322.
Nagamatsu, K., Y. Kido, G. Urakubo et al. 1979. Absorption, distribution, excretion and
metabolism of 2-mercaptobenzothiazole in guinea pig. Eisei Kagaku. 25: 59-65. (Cited in NTP,
1988)
NIOSH (National Institute for Occupational Safety and Health). 2002. NIOSH Pocket Guide to
Chemical Hazards. Online. http://www.cdc.gOv/niosh/npg/.html
NTP (National Toxicology Program). 1988. Technical Report on the Toxicology and
Carcinogenesis Studies of 2-Mercaptobenzothiazole (CAS No. 149-30-4) in F344/N Rats and
B6C3F1 Mice. National Toxicology Program, Research Triangle Park, NC. NTP TR 332. NTIS
PB 88245154. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/A [J. SRCH/iH ATI, SRCH Frames.html
NTP (National Toxicology Program). 2002. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/
OSHA (Occupational Safety and Health Administration). 2002. OSHA Standard 1910.1000
TableZ-1. Part Z, Toxic and Hazardous Substances. Online.
http://www.osha-slc.gov/OshStd data/1910 1000 TABLE Z-l.html
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
4

-------
03-15-05
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC. July.
EPA/540/R-97/036. NTIS 97-921199.
U.S. EPA. 2002. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/
WHO (World Health Organization). 2002. Online Catalogs for the Environmental Criteria
Series. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
5

-------
03-15-05
Provisional Peer Reviewed Toxicity Values for
Anilinobenzothiazole
(CASRN CASRN 1843-21-6)
Derivation of a Carcinogenicity Assessment
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms
bw - body weight
cc - cubic centimeters
CD - Caesarean Delivered
CERCLA - Comprehensive Environmental Response, Compensation, and Liability Act of 1980
CNS - central nervous system
cu.m - cubic meter
DWEL - Drinking Water Equivalent Level
FEL - frank-effect level
FIFRA - Federal Insecticide, Fungicide, and Rodenticide Act
g - grams
GI - gastrointestinal
HEC - human equivalent concentration
Hgb - hemoglobin
i.m. - intramuscular
i.p. - intraperitoneal
i.v. - intravenous
IRIS - Integrated Risk Information System
IUR - Inhalation Unit Risk
kg - kilogram
L - liter
LEL - lowest-effect level
LOAEL - lowest-observed-adverse-efifect level
LOAEL(ADJ) - LOAEL adjusted to continuous exposure duration
LOAEL(HEC) - LOAEL adjusted for dosimetric differences across species to a human
m - meter
MCL - maximum contaminant level
MCLG - maximum contaminant level goal
MF - modifying factor
mg - milligram
mg/kg - milligrams per kilogram
mg/L - milligrams per liter
MRL - minimal risk level
MTD - maximum tolerated dose
1

-------
MTL - median threshold limit
NAAQS - National Ambient Air Quality Standards
NOAEL - no-observed-adverse-effect level
NOAEL(ADJ) - NOAEL adjusted to continuous exposure duration
NOAEL(HEC) - NOAEL adjusted for dosimetric differences across species to a human
NOEL - no-observed-effect level
OSF - Oral Slope Factor
p-RfD - provisional Oral Reference Dose
p-RfC - provisional Inhalation Reference Concentration
p-OSF - provisional Oral Slope Factor
p-IUR - provisional Inhalation Unit Risk
PBPK - physiologically based pharmacokinetic
ppb - parts per billion
ppm - parts per million
PPRTV - Provisional Peer Reviewed Toxicity Value
RBC - red blood cell(s)
RCRA - Resource Conservation and Recovery Act
RGDR - Regional deposited dose ratio (for the indicated lung region)
REL - relative exposure level
RGDR - Regional gas dose ratio (for the indicated lung region)
RfD - Oral Reference Dose
RfC - Inhalation Reference Concentration
s.c. - subcutaneous
SCE - sister chromatid exchange
SDWA - Safe Drinking Water Act
sq.cm. - square centimeters
TSCA - Toxic Substances Control Act
UF - uncertainty factor
ug - microgram
umol - micromoles
VOC - volatile organic compound
11

-------
03-15-05
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
ANILINOBENZOTHIAZOLE (CASRN 1843-21-6)
Derivation of a Carcinogenicity Assessment
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
1

-------
03-15-05
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
A carcinogenicity assessment of anilinobenzothiazole is not available on IRIS (U.S. EPA,
2002a), the HEAST (U.S. EPA, 1997), or the Drinking Water Standards and Health Advisories
list (U.S. EPA, 2002b). No relevant documents were located in the CARA list (U.S. EPA, 1991,
1994). Neither ATSDR (2002), NTP (2002), IARC (2002), nor WHO (2002) have produced
documents regarding anilinobenzothiazole. Literature searches of the following databases were
conducted from 1965 through July 2002 in order to locate relevant studies: TOXLINE,
CANCERLIT, MEDLINE, CCRIS, GENETOX, HSDB, DART/ETICBACK,
EMIC/EMICBACK, RTECS and TSCATS. An updated literature search was conducted through
April 2004 and no relevant information was found.
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REVIEW OF THE PERTINENT DATA
Human Studies
No data regarding the possible carcinogenicity of anilinobenzothiazole in humans were
located.
Animal Studies
No reports of animal studies examining the carcinogenicity of anilinobenzothiazole by
any route of exposure were located.
Other Studies
No data regarding the genotoxicity of anilinobenzothiazole were located.
PROVISIONAL WEIGHT-OF-EVIDENCE CLASSIFICATION
No information was located regarding the carcinogenicity or genotoxicity of
anilinobenzothiazole. It was considered that cancer toxicity values might be obtained by analogy
to 2-mercaptobenzothiazole (MBT), which has toxicity and carcinogenicity information.
However, the pharmacokinetic data on MBT (Colucci and Buyske, 1965; El Dareer et al., 1989;
Larsen et al, 1988; Nagamatsu et al., 1979) do not suggest that biotransformation to
anilinobenzothiazole would occur, and no obvious pathways for biotransformation of
anilinobenzothiazole to MBT were identified. In addition, there is some evidence that the
sulfhydryl group is involved in MBT carcinogenicity (NTP, 1988) and other aspects of MBT
toxicity (Feinman, 1987). Under the proposed U.S. EPA (1999) cancer guidelines, the available
data for anilinobenzothiazole are inadequate for an assessment of human carcinogenic potential.
QUANTITATIVE ESTIMATES OF CARCINOGENIC RISK
Derivation of quantitative estimates of cancer risk for anilinobenzothiazole is precluded
by the lack of data demonstrating carcinogenicity associated with anilinobenzothiazole exposure.
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REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html
Colucci, D.F. and D.A. Buyske. 1965. The biotransformation of a sulfonamide to a mercaptan
and to mercapturic acid and glucuronide conjugates. Biochem. Pharmacol. 14: 457-466.
El Dareer, S.M., J.R. Kalin, K.F. Tillery et al. 1989. Disposition of 2-mercaptobenzothiazole
and 2-mercaptobenzothiazole disulfide in rats dosed intravenously, orally and topically and in
guinea-pigs dosed topically. J. Toxicol. Environ. Health. 27(1): 65-84.
Feinman, S.E. 1987. Sensitivity to rubber chemicals. J. Toxicol.-Cut. Ocular Toxicol. 6(2):
117-153.
I ARC (International Agency for Research on Cancer). 2002. IARC Agents and Summary
Evaluations. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
Larsen, G.L., J.E. Bakke, V.J. Feil and J.K. Huwe. 1988. In vitro metabolism of the methylthio
group of 2-methylthiobenzothiazole by rat liver. Xenobiotica. 18(3): 313-322.
Nagamatsu, K., Y. Kido, G. Urakubo et al. 1979. Absorption, distribution, excretion and
metabolism of 2-mercaptobenzothiazole in guinea pig. Eisei Kagaku. 25: 59-65. (Cited in NTP,
1988)
NTP (National Toxicology Program). 1988. Technical Report on the Toxicology and
Carcinogenesis Studies of 2-Mercaptobenzothiazole (CAS No. 149-30-4) in F344/N Rats and
B6C3F1 Mice. National Toxicology Program, Research Triangle Park, NC. NTP TR 332. NTIS
PB 88245154. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/ALL SRCH/iH ALL SRCH Frames.html
NTP (National Toxicology Program). 2002. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
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U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC. July.
EPA/540/R-97/036. NTIS 97-921199.
U.S. EPA. 1999. Proposed Guidelines for Cancer Risk Assessment. July. Office of Research
and Development, National Center for Environmental Assessment, Washington, DC.
U.S. EPA. 2002a. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/
U.S. EPA. 2002b. 2002 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-02-038. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf
WHO (World Health Organization). 2002. Online Catalogs for the Environmental Criteria
Series. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
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