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Thiophanate-methyl
CASRN 23564-05-8
Contents
0117
Thiophanate-methyl; CASRN 23564-05-8
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 Thiophanate-methyl
File On-Line 01/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 01/01/1992
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 -- Thiophanate-methyl
CASRN -- 23564-05-8
Last Revised -- 01/01/1992
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
-------------------- ----------------------- ----- --- ---------
Decreased body NOEL: 160 ppm 100 1 8E-2
weight, decreased (8 mg/kg/day) mg/kg/day
spermatogenesis, and
histological evidence LEL: 640 ppm
of hyperthyrodism (32 mg/kg/day)
2-Year Rat Feeding
Study
Pennwalt Corp., 1972a
*Dose Conversion Factors & Assumptions: 1 ppm = 0.05 mg/kg/day (rat food
consumption)
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Pennwalt Corporation. 1972a. MRID No. 00032673, 00117868; HED Doc. No.
00200, 00203, 004260. Available from EPA. Write to FOI, EPA, Washington D.C.
20460.
Four groups consisting of 35 male and 35 female SPF. Sprague-Dawley rats were
given diets containing 10, 40, 160, or 640 ppm of thiophanate-methyl. A
control group of 50 males and 50 females was included. The animals were
checked daily for toxic signs and mortality. Body weight and food consumption
were recorded. Hematologic and clinical chemistry testing, and blood analysis
were performed periodically. At sacrifice, organ weight and histopathologic
changes were also reported. The systemic NOEL was 160 ppm (8 mg/kg/day), and
the LEL was 640 ppm (32 mg/kg/day). The treatment caused growth retardation,
decreased spermatogenesis, and histologic evidence of hyperthyroidism.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- A 100-fold uncertainty factor has been used to compensate for the inter-
and intraspecies differences in extrapolating from rats to humans.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Another reproduction study available was concerned only with effects on the
male reproductive system. No effects were found at 195 mg/kg thiophanate-
methyl, although there was an observed increase in adrenal weights (core grade
minimum).
Data Considered for Establishing the RfD
1) 2-Year Feeding (Oncogenic) - rat: Principal study - see discussion above;
core grade minimum
2) 2-Year Feeding - dog: NOEL=50 mg/kg/day; LEL=250 mg/kg/day (growth
retardation, elevated thyroid weight); core grade minimum (Pennwalt Corp.,
1972b)
3) Teratology - rat: Teratogenic NOEL=2500 ppm (125 mg/kg/day) (HDT);
Maternal NOEL=250 ppm (12.5 mg/kg/day), LEL=1200 ppm (60 mg/kg/day); Fetotoxic
NOEL=2500 ppm (HDT); core grade minimum (Atochem North America, Inc., 1985)
4) Teratology - mice: The 1000 mg/kg/day dose caused decreased number of
implantations; core grade supplementary (Incomplete descriptions of protocol,
fetal examinations did not appear to include soft tissue examinations)
(Pennwalt Corp., 1970a)
5) 3-Generation Reproduction - rat: Reproductive NOEL=160 ppm (8 mg/kg/day);
LEL=640 ppm (32 mg/kg/day) (HDT) (reduced litter weights); core grade minimum
(Pennwalt Corp., 1970c)
Other Data Reviewed
1) 2-Year Feeding (Oncogenic) - Mice: Systemic NOEL=160 ppm (22.85
mg/kg/day); core grade minimum (Pennwalt Corp., 1970b)
Data Gap(s): Rabbit Teratology Study
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- High
Data Base -- High
RfD -- High
The principal study appears to be of high quality and is given a high rating.
The data base is very supportive, but has one data gap; therefore, confidence
in the data base can be considered high to medium. Confidence in the RfD can
also be considered high to medium.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Pesticide Registration Files
Agency Work Group Review -- 03/11/1986
Verification Date -- 03/11/1986
___I.A.7. EPA CONTACTS (ORAL RfD)
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).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Thiophanate-methyl
CASRN -- 23564-05-8
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Thiophanate-methyl
CASRN -- 23564-05-8
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- Thiophanate-methyl
CASRN -- 23564-05-8
Last Revised -- 01/01/1992
__VI.A. ORAL RfD REFERENCES
Atochem North America, Inc. 1985. MRID No. 00146643, 92186011; HED Doc. No.
004459. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Pennwalt Corporation. 1970a. MRID No. 0055937; HED Doc. No. 00200, 004260.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Pennwalt Corporation. 1970b. MRID No. 00081611; HED Doc. No. 00200, 00203,
00206, 004260. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Pennwalt Corporation. 1972a. MRID No. 00032673, 00117868; HED Doc. No.
00200, 00203, 004260. Available from EPA. Write to FOI, EPA, Washington, DC
20460.
Pennwalt Corporation. 1972b. MRID No. 00055930, 00057652, 00080282,
00117869; HED Doc. No. 00200, 00203, 004260. Available from EPA. Write to
FOI, EPA, Washington, DC 20460.
Pennwalt Corporation. 1972c. MRID No. 00055931, 00117870, 00057653; HED Doc.
No. 00203, 004260. Available from EPA. Write to FOI, EPA, Washington, DC
20460.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Thiophanate-methyl
CASRN -- 23564-05-8
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/31/1987 IV. Regulatory Action section on-line
03/01/1988 I.A.1. Dose conversion clarified
03/01/1988 I.A.4. Core grades added
03/01/1988 I.A.5. Confidence levels revised
03/01/1988 I.A.6. Documentation revised
01/01/1992 I.A.4. Citations added
01/01/1992 VI. Bibliography on-line
01/01/1992 IV. Regulatory actions updated
VIII. SYNONYMS
Substance Name -- Thiophanate-methyl
CASRN -- 23564-05-8
Last Revised -- 01/31/1987
23564-05-8
ALLOPHANIC ACID, 4,4'-o-PHENYLENEBIS(3-THIO-, DIMETHYL ESTER
BAS 32500F
1,2-BIS(METHOXYCARBONYLTHIOUREIDO)BENZENE
1,2-BIS(3-(METHOXYCARBONYL)-2-THIOUREIDO)BENZENE
o-BIS(3-METHOXYCARBONYL-2-THIOUREIDO)BENZENE
CARBAMIC ACID, (1,2-PHENYLENEBIS(IMINOCARBONOTHIOYL))BIS-, DIMETHYL ESTER
CERCOBIN M
CERCOBIN METHYL
DIMETHYL ((1,2-PHENYLENE)BIS-(IMINOCARBONOTHIOYL))BIS(CARBAMATE)
DIMETHYL-4,4'-o-PHENYLENE-BIS-(3-THIOALLOPHANATE)
ENOVIT M
ENOVIT METHYL
ENOVIT-SUPPER
FRUMIDOR
FUNGITOX
FUNGO
FUNGO 50
LABILITE
METHYLTHIOFANATE
METHYL THIOPHANATE
METHYL TOPSIN
MILDOTHANE
NEOTOPSIN
NF 44
PELT 14
PELT-44
SIGMA
SIPCAPLANT
SIPCASAN
SIPCAVIT
TD 1771
THIOPHANATE M
Thiophanate-methyl
TIOFANATE METILE
TOPSIN M
TOPSIN NF-44
TOPSIN WP METHYL
TREVIN
ZYBAN
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0117.HTM
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