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Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN 19408-74-3
Contents
0166
Hexachlorodibenzo-p-dioxin, mixture (HxCDD); CASRN 19408-74-3
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 HxCDD
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 03/01/1991
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN -- 19408-74-3
Primary Synonym -- 57653-85-7
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN -- 19408-74-3
Primary Synonym -- 57653-85-7
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN -- 19408-74-3
Primary Synonym -- 57653-85-7
Last Revised -- 03/01/1991
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 CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- B2; probable human carcinogen
Basis -- Hepatic tumors in mice and rats by gavage
___II.A.2. HUMAN CARCINOGENICITY DATA
None. There are no published epidemiologic evaluations of hexachloro-
dibenzo-p-dioxin, a contaminant in chlorinated phenols.
___II.A.3. ANIMAL CARCINOGENICITY DATA
Osborne-Mendel rats (50/sex/dose) and B6C3F1 mice (50/sex/dose) were
gavaged with the hexa- chlorodibenzo-p-dioxin mixture suspended in a 9:1 corn
oil:acetone vehicle (NTP, 1980a). Treatment was twice weekly for 104 weeks at
doses of 0, 1.25, 2.5 or 5.0 ug/kg/week for rats and male mice and 0, 2.5, 5
or 10 ug/kg/week for female mice. There were 75 each rats and mice of each
sex as vehicle controls and 25 each female and male rats and mice in the
untreated control group. A dose-related depression in mean body weight gain
was noted in male and female rats. In rats and mice there was a dose-related
toxic hepatitis consisting of degenerative liver changes and necrosis. A
significant dose-related increase in incidence of hepatocellular carcinomas or
neoplastic nodules was noted in male rats. NTP concluded that evidence for
carcinogenicity in male rats was inconclusive. Incidence of hepatocellular
carcinomas, nodules, and adenomas was significantly increased in female rats
relative to vehicle controls both medium- and high-dose). Incidence of
hepatocellular carcinomas and adenomas was increased in a dose-related manner
in male and female mice, reaching statistical significance when the high-dose
males were compared with vehicle controls.
Thirty Swiss-Webster mice/sex were skin-painted with a 2:1 mixture of
1,2,3,6,7,8- and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin in acetone 3 times a
week for 104 weeks (NTP, 1980b). Doses of 0.005 ug/application for the
initial 16 weeks were followed by a 0.01 ug/application for the remainder of
the study. No carcinogenic response related to treatment was observed.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
There are no published reports of genetic toxicology testing of hexa-
chlorodibenzo-p-dioxins.
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
___II.B.1. SUMMARY OF RISK ESTIMATES
Oral Slope Factor -- 6.2E+3 per (mg/kg)/day
Drinking Water Unit Risk -- 1.8E-1 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) 6E-4 ug/L
E-5 (1 in 100,000) 6E-5 ug/L
E-6 (1 in 1,000,000) 6E-6 ug/L
___II.B.2. DOSE-RESPONSE DATA (CARCINOGENICITY, ORAL EXPOSURE)
Tumor Type -- liver tumors (see table)
Test Animals -- mouse, rat (see table)
Route -- gavage
Reference -- NTP, 1980a
Administered Human Equivalent Tumor
Dose (ug/kg/week) Dose (ug/kg/week) Incidence
----------------- ----------------- ---------
mouse/B6C3F1/male (adenomas and carcinomas)
0 0 27/75
vehicle 0 15/73
1.25 0.014 14/50
2.5 0.027 14/49
5.0 0.054 24/48
rat/Osborne-Mendel/female (neoplastic nodules and hepatocellular carcinomas)
0 0 1/73
vehicle 0 2/75
1.25 0.03 5/50
2.5 0.06 7/50
5.0 0.12 18/50
___II.B.3. ADDITIONAL COMMENTS (CARCINOGENICITY, ORAL EXPOSURE)
A geometric mean of the slope factors for male mice and female rats was
used. Slope factors for each species and sex were as follows: male rat =
5.9E+2 per (mg/kg)/day, female rat = 3.5E+3 per (mg/kg)/day, male mouse =
1.1E+4 per (mg/kg)/day, female mouse = 2.9E+3 per (mg/kg)/day. Generally, the
estimate derived from data for most sensitive species/sex was used. In this
case female rat data were also used for the following reasons: 1) the
spontaneous tumor incidence was lower in the rats; 2) statistically
significant increases in incidence were observed at the mid- and high-dose in
rats vs. high-dose only in mice; 3) there was a more distinct dose-response
trend in the rats.
The unit risk should not be used if the water concentration exceeds 6E-2
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 treated and observed for their expected
lifetime. Risk estimates from data sets from two species (see Section
II.B.2.) range within a factor of 20.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
___II.C.1. SUMMARY OF RISK ESTIMATES
Inhalation Unit Risk -- 1.3E+0 (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) 8E-5 ug/cu.m
E-5 (1 in 100,000) 8E-6 ug/cu.m
E-6 (1 in 1,000,000) 8E-7 ug/cu.m
___II.C.2. DOSE-RESPONSE DATA FOR CARCINOGENICITY, INHALATION EXPOSURE
Calculated from oral data in II.B.2. as follows:
Unit risk = 6.2E+3 per (mg/kg)/day x E-3 mg/ug x 0.75 x 20 cu.m/day x
1/70 kg = 1.3/ug/cu.m
where: 6.2E+3 per (mg/kg)/day = oral slope factor
0.75 = assumed percentage of inhaled material
absorbed
20 cu.m/day = assumed breathing rate for adult human
70 kg = assumed weight for adult human
___II.C.3. ADDITIONAL COMMENTS (CARCINOGENICITY, INHALATION EXPOSURE)
The unit risk should not be used if the air concentration exceeds 8E-3
ug/cu.m, since above this concentration the unit risk may not be appropriate.
___II.C.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, INHALATION EXPOSURE)
See II.B.4.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1985
The 1985 Health Assessment Document received both Agency and external review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 01/07/1987
Verification Date -- 01/07/1987
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN -- 19408-74-3
Primary Synonym -- 57653-85-7
Last Revised -- 08/01/1989
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
NTP (National Toxicology Program). 1980a. Bioassay of 1,2,3,6,7,8- and
1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (gavage) for possible carcinogeni-
city. DHHS Publ. No. (NIH) 80-1754.
NTP (National Toxicology Program). 1980b. Bioassay of 1,2,3,6,7,8- and
1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (dermal study) for possible carcino-
genicity. DHHS Publ. No. (NIH) 80-1758.
U.S. EPA. 1985. Health Assessment Document for Polychlorinated Dibenzo-p-
dioxin. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of
Air Quality Planning and Standards, Washington, DC. EPA 600/8/84-014F.
_VII. REVISION HISTORY
Substance Name -- Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN -- 19408-74-3
Primary Synonym -- 57653-85-7
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 II.B.4. Confidence statement revised
03/01/1988 II.C.4. Confidence statement revised
02/01/1989 II.D.3. Primary contact's phone number corrected
08/01/1989 All Primary synonym (CASRN) corrected
08/01/1989 VI. Bibliography on-line
06/01/1990 All Primary synonym (CASRN) corrected again
01/01/1991 II. Text edited
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
03/01/1991 II.A.3. Text edited
VIII. SYNONYMS
Substance Name -- Hexachlorodibenzo-p-dioxin, mixture (HxCDD)
CASRN -- 19408-74-3
Primary Synonym -- 57653-85-7
Last Revised -- 03/31/1987
19408-74-3
57653-85-7
DIBENZO-p-DIOXIN, 1,2,3,6,7,8-HEXACHLORO-
DIBENZO-p-DIOXIN, 1,2,3,7,8,9-HEXACHLORO-
1,2,3,6,7,8-HEXACHLORODIBENZO-p-DIOXIN
1,2,3,7,8,9-HEXACHLORODIBENZO-p-DIOXIN
Hexachlorodibenzo-p-dioxin, mixture
Hexachlorodibenzo-p-dioxin
HxCDD
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0166.HTM
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