Demeton (CASRN 8065-48-3)
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0036
Demeton;
CASRN 8065-48-3
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 Demeton
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 03/01/1988 |
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 — Demeton
CASRN — 8065-48-3
Last Revised — 03/01/1988
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
|
---|---|---|---|---|
ChE inhibition, optic 2-Year Feeding in Mobay Chemical, 1985 |
NOEL: none LEL: 0.8 ppm diet |
1000
|
1
|
4E-5
mg/kg/day |
*Conversion Factors -- 1 ppm = 0.05 mg/kg/day (assumed rat food consumption)
__I.A.2. Principal and Supporting Studies (Oral RfD)
Mobay Chemical Corporation. 1985. MRID No. 00129456, 00146873, 41115401. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Demeton is a mixture of thiol and thiono isomers. The thiol isomer is the same as the oxon metabolite of disulfoton, and the thiono isomer is structurally similar to disulfoton. On this basis, the chronic data submitted for disulfoton were accepted to fulfill requirements for demeton. Since the disulfoton chronic rat study yields the most sensitive endpoint, this study was used for the RfD calculation.
Disulfoton was fed to male and female Fischer 344 rats at 0.8, 3.3, or 13 ppm in the diet for 105 weeks (the intended concentrations were 1, 4, and 16 ppm). Dose-related inhibition of cholinesterase (ChE) was observed for plasma, erythrocyte, and brain in both sexes in all treated groups. Histopathologic changes were observed in both sexes. Optic nerve degeneration was observed in a dose-dependent manner in the low-, mid-, and high-dose females, but was statistically significant only in the mid- and high-dose levels.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 100 was used to account for inter- and intra- species differences in sensitivity to possible optic nerve degeneration. An additional factor of 10 was applied because a NOEL was not established. Based on the 1984 Demeton Registration Standard, the data requirements for chronic testing of Demeton per se were waived, and the chronic data from disulfoton were used as a surrogate.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD
1) 2-Year Feeding (disulfoton) - rat: Principal study - see description above; core grade minimum
2) 2-Year Feeding (disulfoton) - dog: ChE NOEL=1 ppm (0.025 mg/kg/day), ChE LEL=2 ppm (0.05 mg/kg/day); NOEL (other effects)=2 ppm (HDT); core grade minimum (Mobay Chemical, 1975a)
3) 2-Year Feeding (disulfoton) - rat: ChE NOEL=1 ppm (0.05 mg/kg/day), ChE LEL=2 ppm (0.1 mg/kg/day) (RBC and brain ChE inhibition); NOEL (other systemic effects)=none; LEL=2 ppm (males -- higher mortality, increase in both absolute and relative weights of spleen, liver and pituitary, and decrease in both absolute and relative weights of brain and seminal vesicles; females -- decrease in both absolute and relative weight of kidneys); core grade supplementary (Incomplete necropsy and histopathology data) (Mobay Chemical, 1975b)
4) 24-Week Feeding (demeton) - dogs: NOEL=1 ppm (0.025 mg/kg/day); LEL=2 ppm (0.05 mg/kg/day) (inhibition of plasma ChE at 2 ppm, erythrocyte ChE at 5 ppm); core grade supplementary (Ciba-Geigy, 1957)
5) 77 to 112 Day Feeding (demeton) - female rats: ChE NOEL=1 ppm; LEL=3 ppm NOEL (other systemic effects)=10 ppm; LEL=20 ppm (alteration in food intake/body weight ratio); core grade supplementary (Pensalt Chemicals, 1954)
6) 90-Day Feeding Study (demeton)- rats: Systemic NOEL=0.66 mg/kg/day; LEL=0.9 mg/kg/day (tremors and hyperexcitability) (Mobay Chemical, 1955a)
7) 106-Day Feeding (demeton) - rabbits: ChE NOEL=0.15 mg/kg/day; ChE LEL=0.5 mg/kg/day; core grade supplementary (Mobay Chemical, 1955b)
8) Teratology (demeton) - mouse: Developmental NOEL=7 mg/kg/day (i.p. injection); LEL=10 mg/kg/day (i.p.) (possible increase in abnormalities of digestive tract, cleft palate); published report; core grade supplementary (Budreau and Singh, 1973)
Other Data Reviewed:
1) 16-Week Feeding (demeton) - dogs: ChE NOEL=0.75 ppm (0.19 mg/kg/day); LEL=2 ppm (0.05 mg/kg/day); no core grade (Mobay Chemical, 1959)
Data Gaps (demeton): Teratology - rat; Teratology - rabbit; Subchronic feeding - rat; Subchronic feeding- dog; Subchronic feeding on thiolphosphate sulfoxide (plant metabolite)
__I.A.5. Confidence in the Oral RfD
Study — High
Database — Low
RfD — Low
The principal study is of good quality, and is given a high rating. However, the database for demeton is incomplete; therefore, confidence in the data base can be considered low to medium. Confidence in the RfD can also be considered low to medium.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — Pesticide Registration Standard, November 1984; Registration Files.
Agency Work Group Review — 07/22/1986
Verification Date — 07/22/1986
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 Demeton conducted in November 2001 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.
__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 — Demeton
CASRN — 8065-48-3
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Demeton
CASRN — 8065-48-3
This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Demeton
CASRN — 8065-48-3
Last Revised — 01/01/1990
_VI.A. Oral RfD References
Budreau, C.H. and R.P. Singh. 1973. Teratogenicity and embryotoxicity of demeton and fenthion in CF1 mouse embryos. Toxicol. Appl. Pharmacol. 24(2): 324-332.
Ciba-Geigy Corporation. 1957. MRID No. 00061985. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Mobay Chemical Corporation. 1955a. MRID No. 00100906. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Mobay Chemical Corporation. 1955b. MRID No. 00100906. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Mobay Chemical Corporation. 1959. MRID No. 00100908. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Mobay Chemical Corporation. 1975a. MRID No. 00073348. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Mobay Chemical Corporation. 1975b. MRID No. 00069966, 00154957. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Mobay Chemical Corporation. 1985. MRID No. 00129456, 00146873, 41115401. Available from EPA. Write to FOI, EPA, Washington DC 20460.
Pennsalt Chemicals Corporation. 1954. MRID No. 00087465. 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 — Demeton
CASRN — 8065-48-3
Date |
Section |
Description |
---|---|---|
03/31/1987 | IV. | Regulatory Action section on-line |
03/01/1988 | I.A.3. | Text clarified |
03/01/1988 | I.A.4. | Text clarified |
03/01/1988 | I.A.5. | Confidence levels revised |
01/01/1990 | 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 — Demeton
CASRN — 8065-48-3
Last Revised — 01/31/1987
- 8065-48-3
- BAY 10756
- BAYER 8169
- Demeton
- DEMETON-O + DEMETON-S
- DEMOX
- DIETHOXY THIOPHOSPHORIC ACID ESTER of 2-ETHYLMERCAPTOETHANOL
- E 1059
- ENT 17,295
- MERCAPTOPHOS
- O,O-DIETHYL 2-ETHYLMERCAPTOETHYL THIOPHOSPHATE
- O,O-DIETHYL O(and S)-2-(ETHYLTHIO)ETHYL PHOSPHOROTHIOATE MIXTURE
- SYSTEMOX
- SYSTOX
- ULV