United States
Environmental Protection
1=1 m m Agency
EPA/690/R-05/022F
Final
8-05-2005
Provisional Peer Reviewed Toxicity Values for
2,6-T oluenediamine
(CASRN 823-40-5)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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Acronyms and Abbreviations
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-effect 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
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MTD
maximum tolerated dose
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-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
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
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
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PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
2,6-TOLUENEDIAMINE (CASRN 823-40-5)
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 HQ 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.
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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
The HE AST (U.S. EPA, 1997) lists subchronic and chronic RfD values of 2E-1 mg/kg-
day for 2,6-toluenediamine, based on aNOAEL of 16 mg/kg-day in a chronic feeding study in
rats (NCI, 1980). The source document for this assessment was a Health and Environmental
Effects Profile (HEEP) for Selected Toluenediamine (U.S. EPA, 1984). No RfC or cancer
assessment for 2,6-toluenediamine is available in the HEAST (U.S. EPA, 1997) or HEEP (U.S.
EPA, 1984). 2,6-Toluenediamine is not listed on IRIS (U.S. EPA, 2005a) or the Drinking Water
Standards and Health Advisories list (U.S. EPA, 2002). The HEEP is the only relevant
document included in the CARA list (U.S. EPA, 1991, 1994). ATSDR (2003) has not published
a Toxicological Profile that includes 2,6-toluenediamine. An Environmental Health Criteria
Document for Diaminotoluenes (WHO, 1987) is available, but does not include derivation of
quantitative risk values. ACGIH (2003), NIOSH (2003), and OSHA (2003) have not developed
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occupational exposure limits for 2,6-toluenediamine. IARC (2003) has not classified 2,6-
toluenediamine as to possible human carcinogenicity. NCI (1980) conducted a chronic
carcinogenicity bioassay of 2,6-toluenediamine in rats and mice, which served as the basis for the
RfD values in the HEEP (U.S. EPA, 1984) and HEAST (U.S. EPA, 1997). Literature searches
were conducted from 1983 through December, 2004 for studies relevant to the derivation of
provisional toxicity values for 2,6-toluenediamine. Databases searched included: TOXLINE
(supplemented with BIOSIS and NTIS updates), MEDLINE, CANCERLIT, TSCATS, RTECS,
CCRIS, DART, EMIC/EMICBACK, HSDB, and GENETOX.
2,6-Toluenediamine is one of six diaminotoluene isomers that are components of crude or
commercial grade mixtures used as intermediates in the production of dyes and pigments for
commercial products (WHO, 1987). The crude mixture contains all six isomeric forms, while
the two commercial mixtures are composed primarily of two isomers each. One commercial
mixture, meta-diaminotoluene, contains the 2,4- and 2,6- isomers (80:20 or 65:35), and the other,
ortho-diaminotoluene, contains the 2,3- and 3,4- isomers (40:60).
REVIEW OF PERTINENT DATA
Human Studies
No studies of the subchronic or chronic toxicity of 2,6-toluenediamine in humans were
located in the available literature. Epidemiological studies of male workers exposed to
diaminotoluene and dinitrotoluene mixtures were inconclusive as to whether there was an
increased risk of reproductive effects (sperm production and viability of wife's pregnancies were
evaluated) in the exposed workers (WHO, 1987).
Animal Studies
NCI (1980) exposed groups of 10 male and 10 female F344 rats to 0, 100, 300, 1000,
3000 or 10,000 ppm of 2,6-toluenediamine dihydrochloride in the diet for 91 days. Using body
weight data supplied in the study report, U.S. EPA (1988) allometric equations for food
consumption, and adjusting for molecular weight of the dihydrochloride salt, doses of 2,6-
toluenediamine are estimated as 0, 6, 18, 62, 192 or 692 mg/kg-day in male rats, and 0, 7, 20, 70,
221 or 767 mg/kg-day in female rats. Clinical observations were made twice daily and animals
were weighed weekly. At sacrifice, necropsies were performed on all animals and tissues were
taken for histopathologic analysis. This study was conducted as a range-finding study for the
cancer bioassay and a limited number of endpoints were evaluated.
Two out of 10 male rats and 7/10 female rats in the 10,000 ppm group died before the end
of the study; no deaths occurred at any of the other dose levels (NCI, 1980). Body weight gains
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and terminal body weights were depressed in a dose-related fashion in male and female rats (see
Table 1). The reductions in the 3000 and 10,000 ppm groups were markedly larger than in the
lower dose groups. The body weight data were not analyzed statistically by the researchers.
Gross pathological changes, observed in surviving rats in the 10,000 ppm group, were slight to
moderate thyroid enlargement and darkening of the spleen, lymph nodes, liver, kidney, adrenals,
and nasal turbinates. Histological changes were nephrosis in 10,000 ppm males (5/8) and
females (1/7), bone marrow hyperplasia in 10,000 ppm males (8/8) and females (7/7), and
thyroid hyperplasia in 3000 and 10,000 ppm males (7/10 and 8/8, respectively) and 10,000 ppm
females (3/7). No treatment-related lesions were seen in the 1000 ppm or lower dose groups.
Based on large decreases in body weight in males and females and thyroid hyperplasia in males,
the 3000 ppm level (192 mg/kg-day in males and 221 mg/kg-day in females) is a LOAEL and the
1000 ppm level (62 mg/kg-day in males and 70 mg/kg-day in females) a NOAEL in this study.
Table 1. Body Weight in Rats Fed 2,6-Toluenediamine Dihydrochloride in the Diet for 13 Weeks (NCI, 1980)
Dietary Level

Mean Body Weights (g)

Change Relative to Controls (%)
(ppm)
Initial
Final
Gain
Final Body Weight
Body Weight Gain
Male





0
110
298
188
....
....
100
110
271
161
-9
-14
300
110
269
159
-10
-15
1000
110
258
148
-13
-19
3000
110
229
119
-23
-36
10,000
110
158
48
-47
-74
Female





0
98
180
82
....
....
100
98
177
79
-2
-3
300
98
176
78
-2
-5
1000
98
156
58
-13
-29
3000
98
123
25
-32
-70
10,000
98
103
5
-43
-91
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A similar study was performed using B6C3F1 mice (NCI, 1980). However, it is unclear
what dose levels were used. The text reports feeding levels of 0, 10, 30, 100, 300, or 1000 ppm.
This would be consistent with the findings of a 14-day study by the same researchers, which
found a high incidence of death associated with digestive tract hemorrhage in mice fed 3000
ppm. Table 4 of the NCI report, however, lists the dietary concentrations in mice as 0, 100, 300,
1000, 3000, and 10,000 ppm, and the discussion of results seems to correspond to these levels.
No deaths or pathological changes were seen in the mouse study, but body weight gains were
reduced 25-42% and terminal body weights 10-14% versus controls in males of the two high-
dose groups and high-dose females.
NCI (1980) conducted 2-year carcinogenicity bioassays of 2,6-toluenediamine in F344
rats and B6C3F1 mice. Rats (n=50/sex) were exposed to 0, 250 or 500 ppm of 2,6-
toluenediamine dihydrochloride in the diet for 103 weeks, while mice (n=50/sex) were exposed
to 0, 50 or 100 ppm in the diet for 103 weeks. Animals were inspected twice daily, and body
weights were recorded every 4 weeks. At sacrifice or upon death of the animal (provided it was
not precluded by autolysis or cannibalization), gross examination was performed on all major
tissues, and 26 organs and tissues were collected for histologic examination. Using body weight
data graphically supplied in the study report, U.S. EPA (1988) allometric equations for food
consumption, and adjusting for molecular weight of the dihydrochloride salt, doses of 2,6-
toluenediamine are estimated as 0, 12 or 25 mg/kg-day in male rats; 0, 15 or 30 mg/kg-day in
female rats; and 0, 5 or 10 mg/kg-day in male and female mice.
Treatment with 2,6-toluenediamine did not affect survival of rats, which was adequate for
assessment of late-developing tumors (NCI, 1980). Body weight was reduced through much of
the study in high-dose males, and low and high-dose females, in comparison to controls. Time-
weighted average body weights (estimated from graphs in the study report) were approximately
387 g for control and low-dose males and 358 g for high-dose males, indicating a 7% decrease in
the latter. The researchers reported that body weight gains in both treated male groups were
within 10% of controls. For females, estimated time-weighted average body weights were 248 g
in controls, 225 g in the low-dose group (9% decrease), and 221 g in the high-dose group (11 %
decrease). The researchers reported that mean body weight gains in females were reduced 17%
in the low-dose group and 27% in the high-dose group, compared with controls. No treatment-
related clinical signs were reported at any dose level in male or female rats. The incidence of
nonneoplastic lesions in treated rats did not differ significantly from controls. The small
decreases in body weight in treated rats are not considered an adverse effect, making the high
dose of 500 ppm (25 mg/kg-day in males and 30 mg/kg-day in females) a NOAEL in this study.
There was a marginally significant dose-related trend for increased incidence of hepatic
neoplastic nodules or hepatocellular carcinomas in males (0/50, 2/50, 4/50 in the control, low-
and high-dose groups, respectively); however, the researchers did not consider this to be a
treatment-related effect, as none of the treatment groups were significantly different from
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controls in pairwise comparisons (NCI, 1980). Similarly, a dose-related trend was observed for
the incidence of animals with islet-cell adenomas of the pancreas in male rats (0/45, 1/46, 4/45 in
the control, low- and high-dose groups, respectively), but was not considered treatment-related
by the researchers because pairwise comparisons did not attain statistical significance. Other
neoplasms occurred with similar incidence in treated and control rats. The researchers concluded
that 2,6-toluenediamine was not carcinogenic to rats in this bioassay, although it is not clear that
the maximum tolerated dose (MTD) was achieved.
In mice, treatment with 2,6-toluenediamine did not result in any effects on survival
(which was adequate for assessment of late developing tumors in all groups), clinical signs of
toxicity, or body weight or body weight gain (NCI, 1980). No nonneoplastic changes, either at
the gross or microscopic level, could be attributed to treatment with 2,6-toluenediamine. The
high dose of 100 ppm (10 mg/kg-day in both males and females) is a NOAEL in this study.
A slight increase in the incidence of vascular neoplasms (hemangioma/
hemangiosarcoma) of the spleen and liver was seen in male mice (1/50, 5/50, 3/50 in the control,
low- and high-dose groups, respectively), but no dose-related trend was seen, and the differences
were not statistically significant (NCI, 1980). Also in male mice, there was a significant trend
for increased lymphomas relative to controls (2/50, 8/50, 2/50 in the control, low- and high-dose
groups, respectively). However, the only apparent change was in the low-dose group, and the
increase in this group was not statistically significant after adjustment for multiple comparisons.
Female mice showed a significant trend for hepatocellular carcinoma (0/50, 0/49, 3/49 in the
control, low- and high-dose groups, respectively), but the researchers did not consider this
change to be treatment related because pairwise comparisons were not statistically significant.
The researchers concluded that 2,6-toluenediamine was not carcinogenic to mice in this bioassay,
but acknowledged that the MTD was not achieved.
Other Studies
2,6-Toluenediamine is a potent mutagen in Salmonella typhimurium when tested with
metabolic activation (Ashby and Tennant, 1988; Cheung et al., 1996; Cunningham et al., 1989;
Dybing and Thorgeirsson, 1977; Florin et al., 1980; George and Westmoreland, 1991; Sayama et
al., 1989). It is inactive in the absence of activation. In mammalian cells in vitro, 2,6-
toluenediamine was negative in assays for unscheduled DNA synthesis (UDS) in primary
cultured rat hepatocytes (Allavena et al., 1992; Butterworth et al., 1989; Selden et al., 1994), but
was positive for UDS in primary cultured human hepatocytes (Butterworth et al., 1989). Assays
for induction of micronuclei in Chinese hamster ovary (CHO) cells with or without S9 (Miller et
al., 1995) and cell transformation in primary hamster embryo cells (Greene and Friedman, 1980)
were also positive. An assay for DNA fragmentation in cultured rat hepatocytes was negative
(Allavena et al., 1992), but low levels of covalent binding to DNA were reported in another study
in cultured rat hepatocytes (Furlong et al., 1987).
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In vivo, 2,6-toluenediamine did not induce mutations in lacl transgenic male mice
(Hayward et al., 1995). Assays for UDS in hepatocytes isolated from male rats treated with 150
mg/kg of 2,6-toluenediamine by gavage in corn oil (Mirsalis et al., 1982) or 300 mg/kg by
gavage in water (George and Westmoreland, 1991) were negative, but positive results were
obtained in hepatocytes from males rats treated with 2000 mg/kg by gavage in aqueous
carboxymethylcellulose suspension (Allavena et al., 1992). A bone marrow micronucleus assay
in rats was negative at oral doses of 1000-2000 mg/kg in aqueous carboxymethylcellulose
suspension (Allavena et al., 1992), but weak positive results were found in rats treated with 300-
600 mg/kg by gavage in water in another study (George and Westmoreland, 1991), and
intraperitoneal (i.p.) doses as low as 31 mg/kg produced significant increases in bone marrow
micronuclei in mice (Shelby et al., 1993). Assays for detection of DNA fragmentation (alkaline
elution/ electrophoresis) showed no evidence of DNA damage in the liver, kidney, bladder,
colon, stomach, lung, brain or bone marrow of mice treated by oral gavage with 60 mg/kg
(Sasaki et al., 1999) or in the liver of rats treated with 1000 mg/kg orally (Allavena et al., 1992),
but did find significant increases in DNA fragments in rat liver after oral dosing with 2000 mg/kg
(Allavena et al., 1992). Assays for formation of DNA adducts in liver were negative in rats
treated with up to 500 mg/kg i.p. (La and Froines, 1993; Taningher et al., 1995). 2,6-
Toluenediamine (50 mg/kg i.p. 5 days/week for 6 weeks) did not promote preneoplastic liver foci
in partially hepatectomized male rats initiated with diethylnitrosamine (Taningher et al., 1995).
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfD VALUES FOR 2,6-TOLUENEDIAMINE
No studies examining the effects of 2,6-toluenediamine in orally exposed humans were
located. NCI (1980) conducted subchronic and chronic feeding studies in rats and mice. The
subchronic study identified a LOAEL of 3000 ppm (192 mg/kg-day in males and 221 mg/kg-day
in females) in rats based on thyroid hyperplasia in males and large decreases in body weight in
both sexes. Additional effects at the next higher dose of 10,000 ppm (692 mg/kg-day in males
and 767 mg/kg-day in females) were grossly observed thyroid enlargement and darkening of the
spleen, lymph nodes, liver, kidney, adrenals and nasal turbinates; microscopically observed
nephrosis and bone marrow hyperplasia; and death. The NOAEL was 1000 ppm (62 mg/kg-day
in males and 70 mg/kg-day in females). The only changes at this or lower doses were small
decreases in body weight. The results of the chronic rat study are consistent with the subchronic
study. In the chronic study, the high dose of 500 ppm (25 mg/kg-day in males and 30 mg/kg-day
in females) was a NOAEL, with small decreases in body weight being the only effect observed.
Due to poor reporting, the subchronic mouse study cannot be used quantitatively. However, it is
noteworthy that the only effects in this study were small decreases in body weight. The chronic
mouse study found no effects at all at the high dose of 100 ppm (10 mg/kg-day in both males and
females).
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A provisional subchronic RfD of 0.06 mg/kg-day for 2,6-toluenediamine is derived by
applying to the rat oral subchronic NOAEL of 62 mg/kg-day from the NCI (1980) study an
uncertainty factor of 1000 (10 for extrapolation from rats to humans, 10 for protection of
sensitive individuals, and 10 for deficiencies in the database, including lack of reproductive and
developmental toxicity studies), and the quality of the critical study especially the inability to
address all possible adverse outcomes in humans. The subchronic p-RfD follows:
subchronic p-RfD = NOAEL / UF
= 62 mg/kg-day / 1000
= 0.06 or 6E-2 mg/kg-day
Confidence in the principal study is low. The study included an adequate number of dose
groups for male and female rats and mice, but group sizes were only minimally adequate. The
study was conducted as a range-finding study for a cancer bioassay, and only a limited array of
endpoints was evaluated, although histopathology was included. No statistical analyses were
conducted. Reporting of study methods and results was adequate for rats, but poor for the mouse
study. Both a NOAEL and LOAEL were identified for the rat study, but the results of the mouse
study could not be interpreted quantitatively due to the poor reporting. Confidence in the
database is low, as the only supporting study is the chronic cancer bioassay described in the same
report. Overall confidence in the provisional subchronic RfD is low.
A provisional chronic RfD of 0.03 mg/kg-day for 2,6-toluenediamine is derived by
applying to the rat oral chronic NOAEL of 25 mg/kg-day from the NCI (1980) study an
uncertainty factor of 1000 (10 for extrapolation from rats to humans, 10 for protection of
sensitive individuals, and 10 for deficiencies in the database, including lack of reproductive and
developmental toxicity studies), and the quality of the critical study especially the inability to
address all possible adverse outcomes in humans. The chronic p-RfD follows:
p-RfD = NOAEL / UF
= 25 mg/kg-day / 1000
= 0.03 or 3E-2 mg/kg-day
Confidence in the principal study is low. The study included exposure throughout the
two-year study period and adequate numbers of male and female rats and mice in each dose
group, but only two treated groups. The study was performed as a cancer bioassay, and included
only limited evaluation of noncancer endpoints. Statistical analysis of findings was performed
only for cancer-related endpoints. The study did not identify a target organ effect or LOAEL in
either species, indicating that doses tested were too low. Confidence in the database is low, as
the only supporting study is the subchronic range-finding study described in the same report.
Overall confidence in the provisional chronic RfD is low.
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DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfC VALUES FOR 2,6-TOLUENEDIAMINE
No chronic or subchronic inhalation studies examining the effects of 2,6-toluenediamine
in humans or animals were located, precluding derivation of p-RfC values for this chemical.
DERIVATION OF A PROVISIONAL CARCINOGENICITY ASSESSMENT
FOR 2,6-TOLUENEDIAMINE
No data in humans are available to assess the carcinogenic potential of 2,6-
toluenediamine. NCI (1980) evaluated the carcinogenic effects of 2,6-toluenediamine in rats and
mice in two-year feeding studies. No treatment-related neoplasms were seen in males or females
of either species. However, it is not clear that doses used in these studies were appropriate. In
rats, the only effects were small changes in body weight in both dose groups that were not clearly
adverse or related to treatment. In mice, no effects of any type were noted in the treated mice. It,
therefore, appears that doses were too low, such that the MTD was not achieved, in the mouse
study and possibly also the rat study. Consequently, these studies do not rule out the possibility
of a tumorigenic effect of 2,6-toluenediamine at doses higher than those tested. Genotoxicity
studies indicate a strong potential for 2,6-toluenediamine to produce mutations in bacteria with
metabolic activation, and some potential to produce DNA and chromosomal effects in
mammalian cells as well, particularly at high doses. Taking into account the too-low doses in the
negative cancer bioassays in rodents, and the demonstrated genotoxic potential of the chemical,
the available data are considered insufficient to assess the carcinogenic potential of 2,6-
toluenediamine in animals or humans. Under the U.S. EPA (2005b) Guidelines for Carcinogen
Risk Assessment, there is inadequate information to assess the carcinogenic potential of 2,6-
toluenediamine.
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