2,4,6-Trichlorophenol (CASRN 88-06-2)
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0122
2,4,6-Trichlorophenol;
CASRN 88-06-2
Health assessment information on a chemical substance is included in IRIS
only after a comprehensive review of chronic toxicity data by U.S. EPA
health scientists from several Program Offices and the Office of Research
and Development. The summaries presented in Sections I and II represent
a consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR 2,4,6-Trichlorophenol
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | no data | |
Inhalation RfC Assessment (I.B.) | message | 07/01/1991 |
Carcinogenicity Assessment (II.) | on-line | 02/01/1994 |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — 2,4,6-Trichlorophenol
CASRN — 88-06-2
Not available at this time.
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — 2,4,6-Trichlorophenol
CASRN — 88-06-2
The health effects data for 2,4,6-trichlorophenol were reviewed by the
U.S. EPA RfD/RfC Work Group and determined to be inadequate for derivation of
an inhalation RfC. The verification status for this chemical is currently not
verifiable. For additional information on health effects of this chemical,
interested parties are referred to the EPA documentation listed below.
U.S. EPA. 1980. Ambient Water Quality Criteria for Chlorinated Phenols.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Water
Regulations and Standards, Washington, DC.
U.S. EPA. 1983. Reportable Quantity for 2,4,6-Trichlorophenol. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency
Response.
U.S. EPA. 1984. Health Effects Assessment for 2,4,6-Trichlorophenol.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency
and Remedial Response, Washington, DC. PB 86-134582.
U.S. EPA. 1989. Drinking Water Criteria Document for Chlorophenols.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking
Water, Washington, DC.
Agency Work Group Review — 04/24/1991
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfC for 2,4,6-Trichlorophenol conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
EPA Contacts:
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — 2,4,6-Trichlorophenol
CASRN — 88-06-2
Last Revised — 02/01/1994
Section II provides information on three aspects of the carcinogenic assessment for the substance in question; the weight-of-evidence judgment of the likelihood that the substance is a human carcinogen, and quantitative estimates of risk from oral exposure and from inhalation exposure. The quantitative risk estimates are presented in three ways. The slope factor is the result of application of a low-dose extrapolation procedure and is presented as the risk per (mg/kg)/day. The unit risk is the quantitative estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m air breathed. The third form in which risk is presented is a drinking water or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1 in 1,000,000. The rationale and methods used to develop the carcinogenicity information in IRIS are described in The Risk Assessment Guidelines of 1986 (EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries developed since the publication of EPA's more recent Proposed Guidelines for Carcinogen Risk Assessment also utilize those Guidelines where indicated (Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to Section I of this IRIS file for information on long-term toxic effects other than carcinogenicity.
_II.A. Evidence for Human Carcinogenicity
__II.A.1. Weight-of-Evidence Characterization
Classification — B2; probable human carcinogen
Basis — Based on no human data and sufficient evidence in animals; namely,
increased incidence of lymphomas or leukemias in male rats and hepatocellular
adenomas or carcinomas in male and female mice.
__II.A.2. Human Carcinogenicity Data
None.
__II.A.3. Animal Carcinogenicity Data
Sufficient. 2,4,6-Trichlorophenol (96-97% pure) was added to the diet of
50 each male and female F344 rats and B6C3F1 mice (NCI, 1979). In rats 2,4,6-
trichlorophenol was administered at 5000 or 10,000 ppm in feed for 106 or 107
weeks. Male mice also received 5000 or 10,000 ppm of 2,4,6-trichlorophenol
for 105 weeks. Female mice were initially administered 10,000 or 20,000 ppm
of 2,4,6-trichlorophenol in feed. As the animals were observed to have
decreased body weights, these concentrations were lowered to 2500 and 5000 ppm
at week 38 (TWA dose = 5214 or 10,428 ppm). While both rodent species showed
dose-related decreases in mean body weight, no increased mortality nor other
toxic signs were observed.
In male but not female rats, there were dose-related increases in
lymphomas or leukemias which were significantly elevated over controls. The
incidence of lymphomas or leukemias in males was 4/20, 25/50, and 29/50 for
control, low- and high-dose groups, respectively, the majority of which were
leukemias. In some treated male rats in which no leukemia was observed,
leukocytosis and monocytosis of peripheral blood and hyperplasia of the bone
marrow were noted.
In both male and female mice there was a statistically significant trend
in the incidence of combined hepatocellular adenomas and carcinomas.
Pairwise comparisons of the incidence in high- and low-dose male mice and
high-dose female mice with concurrent controls were also statistically
significant. The incidence of carcinomas alone was not significantly
elevated in males, but these data were not given for females. The combined
incidence in the control, low- and high-dose groups for males was 4/20 (20%),
32/49 (65%), and 39/47 (83%) and for females it was 1/20 (5%), 12/50 (24%),
and 24/48 (50%), respectively.
A 20% solution of 2,4,6-trichlorophenol in benzene, applied dermally 2
times/week for 15 weeks, did not promote skin tumors in four strains of mice
(albino Suher, Holtzman, C3H and CAF) initiated with 9,10-dimethyl-1,2-
benzanthracene (Boutwell and Bosch, 1959). In a study of 120 pesticides, both
male and female mice of two strains were gavaged from day 7 to 28 of age with
100 mg 2,4,6-trichlorophenol/kg bw. This was followed by 18 months of dietary
exposure to 260 ppm (approximately 20 to 25 mg/kg total). Four tumor groups
(hepatomas, lymphomas, pulmonary tumors, and total mice with tumors) were
statistically analyzed. The results, pertaining to carcinogenicity, were
reported to be inconclusive and to require further evaluation (No data were
given) (Innes et al., 1969).
Stoner et al. (1986) dosed either intraperitoneally or by gavage, 16 male
and 16 female A/J mice per group with various concentrations of 2,4,6-
trichlorophenol in tricaprylin 3 times/week for 8 weeks. Animals were killed
24 weeks after initiation of dosing. In this short-term assay, the lungs were
histologically examined; other tissues were histologically examined only if
there was evidence of a gross lesion. 2,4,6-trichlorophenol did not induce
lung tumors at cumulative doses of 240, 600, or 1200 mg/kg when administered
intraperitoneally or 1200 mg/kg when administered by gavage.
__II.A.4. Supporting Data for Carcinogenicity
2,4,6-Trichlorophenol in the absence and presence of hepatic homogenates
(S9) was not mutagenic for Salmonella typhimurium (Rasanen et al., 1977;
Kinae et al., 1981). It was mutagenic for Saccharomyces cerevesiae, but had
no effect on mitotic recombination (Fahrig et al., 1978). It has been
reported as mutagenic in the mouse spot test, but is ranked among the weakest
mutagens tested in that assay (Fahrig et al., 1978).
2,4,6-TCP (greater than 99.5% pure) at concentrations up to 100 ug/mL did
not induce mutations to 6-thioguanine resistance in V79 Chinese hamster cells
when tested without exogenous metabolic activation (Jansson and Jansson,
1986). 2,4,6-TCP induced DNA-damage in the Bacillus subtilis rec assay (Kinae
et al., 1981).
_II.B. Quantitative Estimate of Carcinogenic Risk from Oral Exposure
__II.B.1. Summary of Risk Estimates
Slope Factor for Dietary Use — 1.1E-2 per (mg/kg)/day
Drinking Water Unit Risk — 3.1E-7 per (ug/L)
Extrapolation Method — Linearized multistage procedure, extra risk
Drinking Water Concentrations at Specified Risk Levels:
Risk Level
|
Concentration
|
---|---|
E-4 (1 in 10,000)
|
3E+2 ug/L
|
E-5 (1 in 100,000)
|
3E+1 ug/L
|
E-6 (1 in 1,000,000)
|
3E+0 ug/L
|
__II.B.2. Dose-Response Data (Carcinogenicity, Oral Exposure)
Tumor Type: leukemia
Test animals: rat/F344, male
Route: diet
Reference: NCI, 1979
-----------------Dose----------------
|
|||
---|---|---|---|
Administered
(ppm) |
Transformed
Animal Dose (mg/kg/day) |
Human
Equivalent (mg/kg/day) |
Tumor Incidence |
0
|
0
|
0
|
3/20
|
5,000
|
258
|
44.6
|
23/50
|
10,000
|
544
|
94.4
|
29/50
|
__II.B.3. Additional Comments (Carcinogenicity, Oral Exposure)
Dose conversion used a feeding rate of 0.0187 kg/day
and body weights for rats of 0.362 kg and 0.344 for the low and high doses,
respectively. The human equivalent doses were calculated by multiplying
the animal transformed doses by the cube root of the ratio of the rat
body weight to the reference human body weight (70kg). The slope factor
for the hepatocellular carcinoma response in male mice is 2.0E-2 per (mg/kg)/day
(U.S. EPA, 1984), which is about twice the value estimated here for the
rat data.
While the contaminants in the 2,4,6-TCP used in NCI (1979) were not determined,
Firestone et al. (1972) found 49 ppm of 1,3,6,8-TCDD and 93 ppm of 2,3,7-trichlorodibenzo-p-dioxin,
as well as unquantified amounts of tetra-, penta- and hexa-chlorinated
dibenzofurans in commercial grade 2,4,6- trichlorophenol. If the 2,4,6-trichlorophenol
used in NCI (1979) was contaminated with 1,3,6,8-TCDD (less than or equal
to 4%), the liver tumor incidence observed in the NCI (1979) study could
be obscured since this chemical may induce liver tumors. When the Toxic
Equivalency Factor approach (U.S. EPA, 1987) is used, and the same amount
of contamination as shown by Firestone et al. (1972) is assumed, the risk
determined for the development of hepatocellular carcinomas and adenomas
in male mice that is due to this contaminant could theoretically account
for the observed tumors. Confidence in use of this data set for quantitation
is decreased. Since chlorinated dibenzodioxins do not induce leukemia,
the rat data are more appropriate for derivation of the slope factor.
The unit risk should not be used if the water concentration exceeds 3E+4
ug/L, since above this concentration the unit risk may not be appropriate.
__II.B.4. Discussion of Confidence (Carcinogenicity, Oral Exposure)
Adequate numbers of animals were observed for their lifetime.
_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure
__II.C.1. Summary of Risk Estimates
Inhalation Unit Risk — 3.1E-6 per (ug/cu.m)
Extrapolation Method — Linearized multistage procedure, extra risk
Air Concentrations at Specified Risk Levels:
Risk Level
|
Concentration
|
---|---|
E-4 (1 in 10,000) | 3E+1 ug/cu.m |
E-5 (1 in 100,000) | 3E+0 ug/cu.m |
E-6 (1 in 1,000,000) | 3E-1 ug/cu.m |
__II.C.2. Dose-Response Data for Carcinogenicity, Inhalation Exposure
Calculated from oral data in Section II.B.2.
__II.C.3. Additional Comments (Carcinogenicity, Inhalation Exposure)
The unit risk should not be used if the air concentration exceeds 3E+2 ug/cu.m, since above this concentration the unit risk may not be appropriate.
__II.C.4. Discussion of Confidence (Carcinogenicity, Inhalation Exposure)
This inhalation risk estimate was based on oral data.
_II.D. EPA Documentation, Review, and Contacts (Carcinogenicity Assessment)
__II.D.1. EPA Documentation
Source Document — U.S. EPA, 1980, 1984, 1987, 1989
The values in the Ambient Water Quality Criteria Document for Chlorinated
Phenols (1980) received extensive peer and public review. The Drinking
Water Criteria Document on Chlorinated Phenols has received OHEA review.
__II.D.2. EPA Review (Carcinogenicity Assessment)
Agency Work Group Review — 06/26/1986, 10/29/1986,
05/30/1989, 09/07/1989
Verification Date — 09/07/1989
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the cancer assessment for 2,4,6-Trichlorophenol conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__II.D.3. EPA Contacts (Carcinogenicity Assessment)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — 2,4,6-Trichlorophenol
CASRN — 88-06-2
Last Revised — 07/01/1991
_VI.A. Oral RfD References
None
_VI.B. Inhalation RfC References
U.S. EPA. 1980. Ambient Water Quality Criteria for Chlorinated
Phenols. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Water Regulations and Standards, Washington, DC.
U.S. EPA. 1983. Reportable Quantity for 2,4,6-Trichlorophenol. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Solid Waste and
Emergency Response.
U.S. EPA. 1984. Health Effects Assessment for 2,4,6-Trichlorophenol. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Emergency and
Remedial Response, Washington, DC. PB 86-134582.
U.S. EPA. 1989. Drinking Water Criteria Document for Chlorophenols. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Drinking Water,
Washington, DC.
_VI.C. Carcinogenicity Assessment References
Boutwell, R.K. and D.K. Bosch. 1959. The tumor-promoting
action of phenol and related compounds for mouse skin. Cancer Res. 19:
413-424.
Fahrig, R., C.A. Nilsson and C. Rappe. 1978. Genetic activity of chlorophenols
and chlorophenol impurities. In: Pentachlorophenol: Chemistry, Pharmacology
and Environmental Toxicology, K.R. Rao, Ed. Plenum Press, New York. p.
325-338.
Firestone, D., J. Ress, N.L. Brown, R.P. Barron and J.N. Damico. 1972.
Determination of polychlorodibenzo-p-dioxins and related compounds in
commercial chlorophenols. J. Assoc. Off. Anal. Chem. 55(1): 85-92.
Innes, J.R.M., B.M. Ulland, M.G. Valerio, et al. 1969. Bioassay of pesticides
and industrial chemicals for tumorigenicity in mice: A preliminary note.
J. Natl. Cancer Inst. 42(6): 1101-1114.
Jansson, K. and V. Jansson. 1986. Inability of chlorophenols to induce
6-thioguanine-resistant mutants in V79 Chinese hamster cells. Mutat. Res.
171: 165-168.
Kinae, N., T. Hashizume, T. Makita, I. Tomita, I. Kimura and H. Kanamori.
1981. Studies on the toxicity of pulp and paper mill effluents. I. Mutagenicity
of the sediment samples derived from Kraft Paper Mills. Water Research.
15: 17-24.
NCI (National Cancer Institute). 1979. Bioassay of 2,4,6-Trichlorophenol
for Possible Carcinogenicity. U.S. DHEW Publ. No. NCI-CG-TR-155.
Rasanen, L., M.L. Hattula and A.U. Arstila. 1977. The mutagenicity of
MCPA and its soil metabolites, chlorinated phenols, catechols and some
widely used slimicides in Finland. Bull. Environ. Contam. Toxicol. 18(5):
565-571.
Stoner, G.D., P.B. Conran, E.A. Greisiger, J.Stober, M. Morgan and M.A.
Pereira. 1986. Comparison of two routes of chemical administration on
the lung adenoma response in strain A/J mice. Toxicol. Appl. Pharmacol.
82: 19-31.
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Chlorinated
Phenols. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of Water Regulations and Standards, Washington, DC. EPA-440/5-80-032.
NTIS PB- 81-117434.
U.S. EPA. 1984. Health Effects Assessment for 2,4,6-Trichlorophenol. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Emergency and
Remedial Response, Washington, DC. EPA/540/1-86-047. NTIS PB-86-134582/AS.
U.S. EPA. 1987. Interim Procedures for Estimating Risks Associated with
Exposures to Mixtures of Chlorinated Dibenzo-p-dioxins and Dibenzofurans
(CDDs and CDFs). Risk Assessment Forum, Washington, DC. EPA/625/3-87/012.
U.S. EPA. 1989. Drinking Water Criteria Document for Chlorophenols. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Drinking Water,
Washington, DC. (External Review Draft).
_VII. Revision History
Substance Name — 2,4,6-Trichlorophenol
CASRN — 88-06-2
Date |
Section |
Description |
---|---|---|
03/31/1987 | IV. | RQ added |
09/30/1987 | IV. | Regulatory Action section on-line |
03/01/1988 | II.B.1. | Number rounded off |
03/01/1988 | II.B.3. | Text revised |
03/01/1988 | II.B.3. | Water concentration corrected |
03/01/1988 | II.B.4. | Confidence statement revised |
03/01/1988 | II.C.1. | Number rounded off |
03/01/1988 | II.C.4. | Confidence statement revised |
03/01/1988 | II.D.3. | Contacts switched |
07/01/1989 | II. | Carcinogen assessment summary noted as pending change |
10/01/1989 | II. | Withdrawn; new assessment verified (in preparation) |
06/01/1990 | II. | Carcinogen assessment replaced; quant. estimates changed |
06/01/1990 | VI. | Bibliography on-line |
01/01/1991 | II. | Text edited |
01/01/1991 | II.C.1. | Inhalation slope factor removed (global change) |
05/01/1991 | I.B. | Inhalation RfC now under review |
07/01/1991 | I.B. | Inhalation RfC message on-line |
07/01/1991 | VI.B. | Inhalation RfC references added |
01/01/1992 | IV. | Regulatory actions updated |
02/01/1994 | II.D.3. | Primary contact's phone number changed |
04/01/1997 | III., IV., V. | Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information |
12/03/2002 | I.B., II.D.2. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — 2,4,6-Trichlorophenol
CASRN — 88-06-2
Last Revised — 01/31/1987
- 88-06-2
- Dowicide 2S
- NCI-C02904
- Omal
- phenachlor
- Phenol, 2,4,6-trichloro-
- RCRA waste number U231
- 2,4,6-Trichlorophenol
- Trichlorophenol, 2,4,6-