Captafol (CASRN 2425-06-1)
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0216
Captafol;
CASRN 2425-06-1
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 Captafol
File First On-Line 09/30/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 09/30/1987 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Captafol
CASRN — 2425-06-1
Last Revised — 09/30/1987
The oral Reference Dose (RfD) is based on the assumption that thresholds
exist for certain toxic effects such as cellular necrosis. It is expressed
in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the human
population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Please refer
to the Background Document for an elaboration of these concepts. RfDs
can also be derived for the noncarcinogenic health effects of substances
that are also carcinogens. Therefore, it is essential to refer to other
sources of information concerning the carcinogenicity of this substance.
If the U.S. EPA has evaluated this substance for potential human carcinogenicity,
a summary of that evaluation will be contained in Section II of this file.
__I.A.1. Oral RfD Summary
Critical Effect |
Experimental Doses* |
UF |
MF |
RfD |
---|---|---|---|---|
Kidney and bladder One-Year Dog Feeding Ortho-Chevron, 1985a |
NOEL: None LEL: 2 mg/kg/day |
1000
|
1
|
2E-3
mg/kg/day |
*Conversion Factors -- none
__I.A.2. Principal and Supporting Studies (Oral RfD)
Ortho-Chevron Chemical Company. 1985a. MRID No. 00149488, 00155196.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Captafol was administered daily in capsules at 0, 2, 40, and 250 mg/kg bw/day
to male and female beagle dogs for 12 months.
Signs of toxicity occurred primarily at the high dose and were noted in both
sexes, except where specified: emesis, soft compound colored feces, body
weight gain depression (mid and high doses), decreased BUN (males), decreased
LDH (males), decreased inorganic phosphorus (males), decreased albumen (mid
and high doses, males), slight increase in centrolobular hepatic inflammation
(males), and ballooning degeneration/vacuolation of the transitional
epithelium of the kidney and bladder (low, mid and high doses, females). The
incidence and severity of the transitional epithelial lesion was dose-related.
Although there was no NOEL, and this lesion occurred at the lowest dose
tested, 2 mg/kg/day will be considered the LEL for this effect and the study
as a whole because the incidence and frequency decreased to minimal in the
lowest dose.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The UF of 100 includes uncertainties in the extrapolation from
laboratory animals to humans and to protect sensitive individuals. An
additional UF of l0 was used to account for the fact that the RfD is based on
the LEL from the chronic dog study rather than a NOEL.
MF — None
__I.A.4. Additional Comments (Oral RfD)
Data Considered for Establishing the RfD:
1) 1-Year Feeding - dog: Principal study - see previous description; core
grade guideline
2) 2-Year Feeding (oncogenic) - rat: Systemic NOEL=2.8 mg/kg/day bw*;
Systemic LEL=12.0 mg/kg/day* (hyperplasia of renal transitional epithelium and
altered gastric mucosa); core grade minimum (Chevron Chemical, 1985b)
3) Teratology - rabbit: Maternal NOEL=4 mg/kg/day; Maternal LEL=16 mg/kg/day
(decreased weight gain and food consumphtion); Fetotoxic NOEL=16.5 mg/kg/day;
LEL=50.0 mg/kg/day (increased minor skeletal abnormalities and resorptions);
core grade minimum (Chevron Chemical, 1984)
4) Teratology - rat: Maternal NOEL=30 mg/kg/day; Maternal LEL=200 mg/kg
(mortality, gastric lesions, decrease in body weight, weight gain, and food
consumption); Fetotoxic NOEL=30 mg/kg/day; Fetotoxic LEL=200 mg/kg/day
(decreased fetal weight and ossification sites); core grade minimum (Chevron
Chemical, 1983a)
5) 2-generation Reproduction - rat: Maternal NOEL=13 mg/kg/day; LEL=60
mg/kg/day (lower mean body weight); Fetotoxic NOEL=60 mg/kg/day (HDT);
Fetotoxic LEL=none; core grade minimum (Chevron Chemical, 1983b)
* average measured captafol concentration
Other Data Reviewed:
1) 2-Year (oncogenic) - mice: Systemic NOEL=15 mg/kg/day; Systemic LEL=50
mg/kg/day (decreased body weight, atrophy of pancreas, testicles, spleen, bone
marrow, and kidney; core grade minimum (Chevron Chemical, 1985c)
Data Gap(s): None
__I.A.5. Confidence in the Oral RfD
Study — High
Database — High
RfD — High
The principal study appears to be of good quality and is given a high confidence rating. Additional studies are of fair to good quality, and there are no data gaps; therefore, the database is given a high confidence rating. High confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Standard, September 1986
Pesticide Registration Files
Agency Work Group Review — 04/22/1986, 05/20/1987
Verification Date — 05/20/1987
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for Captafol conducted in September 2002 identified one or more significant new studies. IRIS users may request the references for those studies from the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__I.A.7. EPA Contacts (Oral RfD)
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).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Captafol
CASRN — 2425-06-1
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Captafol
CASRN — 2425-06-1
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Captafol
CASRN — 2425-06-1
Last Revised — 11/01/1989
_VI.A. Oral RfD References
Ortho-Chevron Chemical Company. 1983a. MRID No. 00132556. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Ortho-Chevron Chemical Company. 1983b. MRID No. 00119072. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Ortho-Chevron Chemical Company. 1984. MRID No. 00160970. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Ortho-Chevron Chemical Company. 1985a. MRID No. 00149488, 00155196.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ortho-Chevron Chemical Company. 1985b. MRID No. 00129987, 00144563.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ortho-Chevron Chemical Company. 1985c. MRID No. 00144564, 00150103,
00150108. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
_VI.B. Inhalation RfD References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Captafol
CASRN — 2425-06-1
Date |
Section |
Description |
---|---|---|
11/01/1989 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory actions updated |
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.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Captafol
CASRN — 2425-06-1
Last Revised — 09/30/1987
- 2425-06-1
- Captafol
- CAPTATOL
- CAPTOFOL
- 4-CYCLOHEXENE-1,2-DICARBOXIMIDE, N-((1,1,2,2-TETRACHLOROETHYL)THIO)-
- DIFOLATAN
- DIFOSAN
- FOLCID
- N-(1,1,2,2-TETRACHLORAETHYLTHIO)-CYCLOHEX-4-EN-1,4-DIACARBOXIMID
- N-(1,1,2,2-TETRACHLORAETHYLTHIO)-TETRAHYDROPHTHALAMID
- N-1,1,2,2-TETRACHLOROETHYLMERCAPTO-4-CYCLOHEXENE-1,2-CARBOXIMIDE
- N-((1,1,2,2-TETRACHLOROETHYL)SULFENYL)-cis-4-CYCLOHEXENE-1,2-DICARBOXIMIDE
- N-(1,1,2,2-TETRACHLOROETHYLTHIO)-4-CYCLOHEXENE-1,2-DICARBOXIMIDE
- ORTHO 5865
- SANSPOR
- SULFONIMIDE
- SULPHEIMIDE