540186047
United States
Environmental Protection
Agency
Of/tee of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
&EPA
'HEALTH EFFECTS ASSESSMENT
FOR 2,4,6-TRICHLOROPHENOL
Do not remove. This document
should be retained in the EPA
Region 5 Library Collection.
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EPA/540/1-86-047
September 1984
HEALTH EFFECTS ASSESSMENT
FOR 2,4,6-TRICHLOROPHENOL
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with
2,4,6-trlchlorophenol. All estimates of acceptable Intakes and carcinogenic
potency presented 1n this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data
bases. The basic literature searched supporting this document 1s current up
to September, 1984. Secondary sources of Information have also been relied
upon In the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) source has
been extensively utilized:
U.S. EPA. 1980b. Ambient Water Quality Criteria for Chlorinated
Phenols. Environmental Criteria and Assessment Office, Cincinnati,
OH. EPA 440/5-80-032. NTIS PB 81-117-434.
The Intent In these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer Is not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, Is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants In ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
The AIC, acceptable Intake chronic, 1s similar In concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980a) for a discussion
of this concept]. The AIC Is route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes Is Insignificant.
111
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Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development 1s explained 1n U.S. EPA (1983).
For compounds for which there 1s sufficient evidence of carclnogenlcHy,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer 1s a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment 1n proper context, the reader 1s
referred to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate
Interpretation and use of the quantitative estimates.
2,4,6-TMchlorophenol has been shown to be carcinogenic 1n both rats and
mice following oral administration. Data are not available which address
the carclnogenldty of this compound 1n human populations. Limited mutagen-
IcHy testing has yielded mixed results. Using data for hepatocellular
carcinoma and adenoma Incidence 1n male mice, a q-|* of 1.98xl(T2
(mg/kg/day)"1 was calculated. No data are available which address the
potential carclnogenldty of this compound by the Inhalation route.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Or. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was'»the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and-Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
7.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . . .
2.1. ORAL
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
3.2. CHRONIC
3.2.1. Oral
3.2.2. Inhalation
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.4. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.2. BIOASSAYS
4.3. OTHER RELEVANT DATA
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT •
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.3. CARCINOGENIC POTENCY (q-|*)
6.3.1. Oral
6.3.2. Inhalation
REFERENCES
Page
, , 1
3
, . . 3
, ,. 3
4
. , 4
, . . 4
6
6
. . . 6
7
. . . 8
8
9
. . . 9
g
. . . 13
, . . 13
14
. . . 15
. . . 15
, . . 15
, . . 15
. . . 15
. . . 15
. . . 16
APPENDIX: Summary Table for 2,4,6-TMchlorophenol 19
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
bw Body weight
CAS Chemical Abstract Service
CS Composite score
MED Minimum effective dose
ppm Parts per million
RV0 Dose-rating value
RVe Effect-rating value
TWA Time-weighted average
V111
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Relevant physical and chemical properties and environmental fate of
2,4,6-tMchlorophenol (CAS No. 88-06-2) are as follows:
Chemical class:
Molecular weight:
Vapor pressure:
(estimated)
Water solubility:
Log octanol/water
partition coefficient:
B1oconcentrat1on
factor:
Half-life 1n A1r:
Water:
Soil:
halogenated phenol
197.46
0.012 mm Hg at 25°C
800 mg/a, at 25°C
3.87
310 1n Golden orfe
(Leudsens 1dus
melanotus)
<1 day (estimated)
<1-19 days (estimated)
5 days for complete
blodegradatlon
Verschueren, 1983
Mabey et al.. 1981
Verschueren, 1983
U.S. EPA, 1980b
Freltag et al.,
1982
Verschueren, 1983
The half-life for 2,4,6-tMchlorophenol 1n the atmosphere 1s estimated
from Us relative photodecomposHlon rate (silica gel coated material) with
respect to the photodecomposHlon of pentachlorophenol as determined by
Freltag et al. (1982) and the half-life for photodecomposHlon of penta-
chlorophenol 1n aquatic media as estimated by Callahan et al. (1979). The
lower value for the half-life range In aquatic media as given above Is based
on considerations similar to those of atmospheric photodecomposHlon. In
aquatic media, however, photodecomposHlon may become less significant as
the water depth Increases because of light scattering and resulting attenu-
ation. Therefore, precipitation through adsorption onto partlculate matter
-1-
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(Freitag et al., 1982} and blodegradatlon may play significant roles 1n
determining the fate of this chemical 1n certain bodies of water. The upper
value for the half-life range has been speculated from the estimated
blotransformatlon rate constant (3xlO~9 ml cell"1 hr"1) reported by
Mabey et al. (1981) and the concentration of microorganisms at 5xlOs cells
miT1 (Burns et al., 1982).
The octanol/water partition coefficient value Indicates that this
compound may be sorbed significantly to soils with high organic carbon
content. In sandy soils, 2,4,6-trlchlorophenol may have significant mobil-
ity. The b1odegradab1!1ty of this compound 1n soils may prevent substantial
contamination of groundwater because of leaching.
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' 2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL MAMMALS
2.1. ORAL
No quantitative studies of gastrointestinal absorption of 2,4,6-trl-
chlorophenol have been found 1n the available literature; however, Dougherty
and Plotrowska (1976) suggested that chlorophenols as a chemical class tend
to be excreted rapidly through the urine and, therefore, urinary concentra-
tions should reflect exposure. Quantitative analyses were not performed 1n
this study.
2.2. INHALATION
Pertinent data regarding the absorption of 2,4,6-trlchlorophenol follow-
ing Inhalation exposure could not be found 1n the available literature.
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. No reports of toxldty 1n humans associated with subchronlc
oral exposure to 2,4,6-tMchlorophenol could be found 1n the available
literature. The only investigation of the subchronic oral toxicity to
animals of 2,4,6-trichlorophenol was a range-finding experiment by the NCI
(1979) preliminary to performing an oral carcinogenicity bioassay. In this
study, groups of five male and five female Fischer 344 rats were fed ad.
libitum diets that contained 0, 10,000, 14,700, 21,500, 31,500 or 46,000 ppm
2,4,6-trichlorophenol for 7 weeks followed by 1 additional week of observa-
tion. Mortality, body weights and histopathological evaluation of selected
organs were the parameters of toxicity that were monitored. Groups of five
B6C3F, mice of each sex were also fed ad libitum diets containing 0, 6800,
10,000, 14,700, 21,500 or 31,500 ppm 2,4,6-trichlorophenol for 7 weeks
followed by an additional 1-week observation period. The same parameters of
toxicity were monitored 1n mice as 1n rats.
Body weight and survival data for both rats and mice are presented in
Table 3-1. Mean body weights for treated rats and mice of each sex were
considerably lower than those of corresponding controls. This trend ap-
peared to be strongly dose-related, although statistical analyses were not
performed. In rats, histopathological lesions were found only in the high-
dose groups and consisted of moderate to marked increases in splenic hemato-
poiesls 1n rats of each sex and mldzonal vacuollzatlon of hepatocytes in two
male rats. All tissues from mice exposed to diets containing 21,500 ppm
2,4,6-trichlorophenol appeared to be essentially normal. The evaluation of
toxldty was insufficient to enable this study to be used in quantitative
risk assessment.
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TABLE 3-1
2,4,6-Trlchlorophenol Subchronlc Feeding Studies 1n Rats and M1cea
Male
Dose
(ppm)
Rats
0
10,000
14,700
21,500
31,500
46,000
Mice
0
6,800
10,000
14,700
21.500
31,500
Survival*5
5/5
5/5
5/5
4/5
4/5
3/5
5/5
5/5
5/5
5/5
5/5
3/5
Mean Weight
at Week 7
as % of
Control
100
96
89
73
47
39
100
99
99
83
79
57
Female
Surv1valb
5/5
5/5
5/5
5/5
4/5
2/5
4/5
5/5
5/5
5/5
5/5
3/5
Mean Weight
at Week 7
as % of
Control
100
92
84
73
67
42
100
no
no
101
93
68
aSource: NCI, 1979
^Number surviving/number 1n group
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3.1.2. Inhalation. Pertinent data regarding toxldty 1n humans or
animals related to Inhalation exposure to 2,4,6-trlchlorophenol could not be
located 1n the available literature.
3.2. CHRONIC
3.2.1. Oral. No reports of toxldty 1n humans chronically exposed to
2,4,6-trlchlorophenol by the oral route could be found 1n the available
literature. Likewise, no Investigations of chronic oral toxldty of 2,4,6-
trlchlorophenol 1n laboratory animals suitable for quantitative risk assess-
ment could be found 1n the available literature.
BRL (1968) administered commercial grade 2,4,6-trlchlorophenol (Impur-
ities unspecified) to groups of 18 male and 18 female C57B1/6 x C3H/Anf FI
mice and 18 male and 18 female C57B1/6 x AKR FI mice. From 7-28 days of
age, mice were treated by gavage with 100 mg 2,4,6-trlchlorophenol 1n 0.5%
gelatin/kg bw. The amount administered remained unchanged; adjustments for
changes 1n body weight were not made. At 28 days of age, gavage treatment
was discontinued and all four groups of mice were exposed to diets contain-
ing 260 ppm 2,4,6-trlchlorophenol. Treatment was continued to 78 weeks of
age. Survival was the only parameter of toxldty evaluated. At the end of
the experiment, survival In the above four groups was 10/18, 16/18, 16/18
and 17/18, respectively. Tumor data are reported 1n Section 4.2.
The NCI (1979) completed a cardnogenldty bloassay 1n which groups of
50 male and 50 female Fischer F344 rats were exposed to 5000 or 10,000 ppm
2,4,6-trlchlorophenol 1n the diet for 106-107 weeks. Matched controls con-
sisted of 20 untreated rats of each sex. Groups of 50 male B6C3F, mice
were fed diets containing 5000 or 10,000 ppm 2,4,6-trlchlorophenol for 105
weeks. Groups of 50 female B6C3F, mice were fed diets containing 10,000
or 20,000 ppm 2,4,6-trlchlorophenol for 38 weeks. Because of severe body
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weight loss 1n the treated female mice, dosages were reduced to 2500 and
5000 ppm, respectively, and treatment was continued for an additional 67
weeks. Matched controls consisted of 20 untreated mice of each sex. Body
weights were recorded monthly; all animals were subjected to necropsy at
death (unless cannibalized), when moribund or at the termination of the
experiment.
Treated rats of each sex exhibited mean body weights lower than those of
matched controls. Statistical analyses of body weight data were not report-
ed; however, estimates of the probability of survival for treated male and
female rats and for matched controls were subjected to statistical analysis.
No significantly dose-related trend In mortality In rats of either sex was
found by the Tarone test. Other clinical signs of toxldty (not specified)
were common to both treated and control groups.
Mean body weights of treated mice of each sex were lower than those of
corresponding controls and were dose-related throughout the experiment. By
the Tarone test, no significant dose-related trend 1n mortality was found In
mice of either sex. Other clinical signs of toxldty (not specified) were
common to both treated and control groups.
The Incidence of neoplasms associated with 2,4,6-tMchlorophenol 1n this
bloassay Is discussed 1n Section 4.2.
3.2.2. Inhalation. No reports of toxldty 1n humans or animals
associated with chronic Inhalation exposure to 2,4,6-trlchlorophenol could
be found In the available literature.
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3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
No reports could be found In the available literature associating
teratogenlcHy, fetotoxldty or reproductive toxlclty with oral or Inhala-
tion exposure to 2,4,6-tMchlorophenol.
3.4. TOXICANT INTERACTIONS
No studies of the Interactions of 2,4,6-tMchlorophenol with other
xenoblotlcs could be found 1n the available literature.
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4. CARCINOGENICITY
4.1. HUMAN DATA
No reports of cancer 1n humans associated specifically with 2,4,6-tri-
chlorophenol have been found 1n the available literature.
4.2. BIOASSAYS
An oral bloassay 1n (C57B1/6 x C3H Anf) FI mice and (C57B1/6 x AKR)
F, mice has been performed by BRL (1968). The experimental protocol and
survival data to 78 weeks of age are discussed In Section 3.2.1. Among
C57B1/6 x C3H Anf F, mice the tumor Incidence was 9/18 for males and 7/18
for females (types of tumors not specified). Among C57B1/6 x AKR F.. mice,
tumors were found In 3/17 males and 2/17 females. In pooled controls,
tumors were found In 22/79, 8/87, 16/90 and 7/82 In C57B1/6 x C3H Anf F]
males and females and in C57B1/6 x AKR F, males and females, respectively.
Statistically significant Increases (p<0.05) 1n the Incidences of hepatomas
(5/36) and retlculum cell sarcomas (6/36) were observed in C57B1/6 x C3H Anf.
F, mice when the numbers of tumors in males and females were combined and
compared with pooled controls. IARC (1979) noted that the statistical
significance disappears when the Incidence of tumors 1n males and females
are considered separately or when incidences of tumors in treated mice are
compared with the Incidences in matched controls.
The NCI (1979) has completed an oral bloassay in Fischer F344 rats and
B6C3F, mice. The details of the protocol were discussed in Section
3.2.1. Fifty rats of each sex and groups of 50 male mice were fed ad_
libitum with diets containing 5000 or 10,000 ppm 2,4,6-trichlorophenol for
105-107 weeks. In addition, 50 female mice were exposed initially to diets
containing 10,000 or 20,000 ppm 2,4,6-trichlorophenol for 38 weeks, and
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subsequently to diets containing 2500 or 5000 ppm for an additional 67
weeks. TWA exposures 1n female mice were 5214 and 10,428 ppm
2,4,6-trlchlorophenol, respectively.
In rats, the Incidence of neoplasms of the hematopoletlc system, lym-
phoma and monocytlc leukemia appeared to be treatment-related. These data
are detailed 1n Table 4-1. The elevated Incidence of monocytlc leukemia In
male rats was statistically significant, with p values for the Fisher exact
test of 0.013 and 0.002 associated with the low- and high-dose groups,
respectively. The Cochran-Armltage test for a positive dose-related trend
was also significant (p=0.003). The Incidence of monocytlc leukemia In
female rats was not statistically significant by either test. The NCI
(1979) stated that the "statistical conclusion 1s that the Incidence of
[monocytlc leukemia] 1n male rats 1s associated with the administration of
2,4,6-trichlorophenol."
In mice, the incidence of hepatocellular neoplasms appeared to be high
in all treated groups but especially high in the two groups of treated male
mice, where most of the livers were affected. These data are summarized in
Table 4-2. In male mice the elevated incidence of hepatocellular neoplasms
(carcinomas or adenomas) in either treated group was significant (p<0.001)
by the Fisher exact test when compared with controls. The result of the
Cochran-Armitage test for a positive dose-related trend for hepatocellular
neoplasia in male mice was also highly significant (p<0.001). The elevated
Incidence of hepatocellular carcinoma 1n treated female mice was significant
by the Cochran-Armltage test (p=0.005) but not by the Fisher exact test.
When the incidence of hepatocellular carcinoma or adenoma 1n treated female
mice was compared with the incidence of these tumors in control mice the
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TABLE 4-1
Incidence of Neoplasla of the Hematopoletlc System
In Male and Female Rats Exposed to 2,4,6-TMchlorophenol*
Males
Females
Control Low-Dose High-Dose Control Low-Dose High-Dose
Number of 20
animals
necropsled
Malignant 1 (5%)
lymphoma
Monocytlc 3 (15%)
leukemia
Fisher
exact
NR
50
2 (4%)
50
0 (0%)
20
50
50
0 (0%) 0 (054) 2 (4%)
23 (46%) 29 (58%) 3 (15%) 11 (22%) 11 (22%)
(p=0.013) (p=0.002) NR
Cochran- (p=0.003)
Armltage
test
NR
NR
NS
NS
NR
NS
NR
*Source: NCI, 1979
NS = Not statistically significant; NR = Not reported
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TABLE 4-2
Incidence of Hepatic Neoplasla 1n Male and Female Mice Exposed to 2,4,6-Trlchlorophenol*
Number of animals
with tissues examined
microscopically
Hepatocellular
adenoma
Hepatocellular
carcinoma
Fisher exact test
Cochran-Armltage
test
Total hepatocellular
tumors
Fisher exact test
Cochran-Armltage test
Control
20
3 (1554)
1 (5%)
NR
NS
4 (2054)
NR
(p<0.001)
Hales
Low Dose
49
22 (45%)
10 (20%)
NS
NR
32 (65%)
(p<0.001)
NR
•
High Dose
47
32 (68%)
7 (15%)
NS
NR
39 (83%)
(p<0.001)
NR
Control
20
1 (5%)
0 (0%)
NR
(p-0.005)
1 (5%)
NR
(p<0.001)
Females
Low Dose
50
12 (24%)
0 (0%)
NS
NR
12 (24%)
NS
NR
High Dose
48
17 (35%)
7 (15%)
NS
NR
24 (50%)
(p<0.001)
NR
*Source: NCI, 1979
NS = Not statistically significant; NR = Not reported
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Fisher exact test was significant for the high-dose group (p<0.001) and the
Cochran-Armltage test Indicated (p<0.01) a positive dose-related trend.
Data regarding the Incidence of hepatocellular carcinomas and adenoma 1n
male mice were selected by the U.S. EPA (1980b) for derivation of a q^
(Section 6.3.1.).
4.3. OTHER RELEVANT DATA
Negative results for mutagenldty 1n the Ames Salmonella typhlmurlum
bloassay were obtained for 2,4,6-tMchlorophenol both with and without the
addition of rat hepatic S9 activation (Rasanen et a!., 1977). In S.
cerevlslae strain MP-1, 2,4,6-trlchlorophenol Increased the mutation rate
but not the rate of Intragenlc recombination (FahMg et al., 1978).
4.4. WEIGHT OF EVIDENCE
No reports of cancer 1n humans linked to 2,4,6-trlchlorophenol have been
found 1n the available literature. The significant (p<0.05) Incidence of
"total tumors" 1n C57B1/6 x C3H Anf F] mice compared with pooled controls
In the study by BRL (1968) suggested that 2,4,6-trlchlorophenol may be
carcinogenic. The NCI (1979) bloassay discussed 1n Section 4.2. Indicated
that monocytlc leukemia 1n male rats was associated with dietary Intake of
2,4,6-trlchlorophenol. In both male and female mice, the Incidence of
hepatocellular neoplasla (adenoma and carcinoma) was significantly (p<0.001)
linked to dietary exposure to 2,4,6-trlchlorophenol. Judging the degree of
evidence for cardnogenldty 1n humans to be Inadequate and the degree of
evidence for cardnogenldty In animals to be adequate, 2,4,6-trlchloro-
phenol 1s most appropriately classified according to the criteria proposed
by the Carcinogen Assessment Group of the U.S. EPA (Federal Register, 1984)
1n Group B2 - Probable Human Carcinogen.
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5. REGULATORY STANDARDS AND CRITERIA
No current standards or recommended criteria for 2,4,6-trlchlorophenol
1n air were found 1n the available literature. The U.S. EPA (19805) has not
recommended an ambient water quality criterion for 2,4,6-trlchlorophenol
based on chronic toxldty because of the carcinogenic nature of this com-
pound. An acceptable concentration of 12 yg/9, based on an Increased
carcinogenic potency was recommended. A criterion to protect against
organoleptlc effects of 2.0 yg/S. was also proposed, based on the data of
DeHz and Traud (1978).
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
2,4,6-TMchlorophenol 1s a chemical known to be carcinogenic 1n animals
and for which data are adequate for derivation of a q *. It 1s Inappro-
priate, therefore, to calculate an AIS for 2,4,6-trlchlorophenol.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
2,4,6-Trlchlorophenol 1s a chemical known to be carcinogenic In animals
and for which data are adequate for derivation of a q,*. It 1s Inappro-
priate, therefore, to calculate an AIC for 2,4,6-trlchlorophenol.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. Dietary treatment of male mice with TWA concentrations of
5000 and 10,000 ppm 2,4,6-trlchlorophenol resulted 1n a highly significant
(p<0.001 by both the Fisher exact and the Cochran-ArmHage tests) elevated
Incidence of hepatocellular carcinomas or adenomas when compared with
nontreated matched controls. From these data, summarized 1n Appendix B, the
U.S. EPA (1980b) calculated a q^ for humans of 1.98xlO~2 (mg/kg/
day)'*.
6.3.2. Inhalation. No reports of cardnogenldty 1n humans or animals
related to Inhalation exposure to 2,4,6-trlchlorophenol were located 1n the
available literature; therefore, no q * or carcinogenic potency for
Inhalation exposure of 2,4,6-trlchlorophenol can be calculated.
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7. REFERENCES
BRL (B1onet1cs Research Laboratories). 1968. Evaluation of the Carcino-
genic, Teratogenlc and Mutagenlc Activities of Selected Pesticides and
Industrial Chemicals. Vol. 1. Carcinogenic Study, Publication No.
NCIOCCP-CG-1973-1-1. Prepared by BRL, Bethesda, MD, under Contract No. PH
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APPENDIX A
Summary Table for 2,4,6-Trlchlorophenol*
Carcinogenic
Potency
Species
Experimental
Dose/Exposure
Effect
Inhalation
Oral
mouse 5000 and
10,000 ppm
(650 and 1300
mg/kg/day)
hepatocellular
carcinoma and
adenoma
ND
1.98xlO~2
{mg/kg/day)"1
*Source: NCI, 1979
ND = Not derived
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APPENDIX B
Cancer Data Sheet for Derivation of q-j*
Compound: 2,4,6-tMchlorophenol
Reference: NCI, 1979
Species, Strain, Sex: mice, B6C3F1, male
Body weight: 0.04 kg (measured)
Length of exposure (le) = 735 days
Length of experiment (Le) = 735 days
Llfespan of animal (L) = 735 days
Tumor site and type: liver, hepatocellular adenoma and carcinoma
Route, vehicle: oral, diet
Experimental Doses
or Exposures
(PPm)
0
5000
10,000
Transformed Dose
(mg/kg/day)
0
650
1300
Incidence
No. Responding/No.
or Examined
4/20
32/49
39/47
Tested
Unadjusted q-j* from study = 1.61xlO~3 (mg/kg/day) 1
Human q^* = 1.98xlO~2 (mg/kg/day)'1
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