Tetraethyldithiopyrophosphate (CASRN 3689-24-5)
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0330
Tetraethyldithiopyrophosphate; CASRN 3689-24-5
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 Tetraethyldithiopyrophosphate
File First On-Line 09/07/1988
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 02/01/1995 |
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 — Tetraethyldithiopyrophosphate
CASRN — 3689-24-5
Last Revised — 02/01/1995
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 |
---|---|---|---|---|
Depressed RBC and Rat Subchronic Oral Kimmerle and Klimmer, |
NOEL: 10 ppm diet LOAEL: 20 ppm diet |
1000
|
1
|
5E-4
mg/kg/day |
*Conversion Factors: Assumed rat food consumption = 5% body weight/day
__I.A.2. Principal and Supporting Studies (Oral RfD)
Kimmerle, G. and O.R. Klimmer. 1974. Acute and subchronic toxicity of Sulfotep. Arch. Toxicol. 33(1): 1-16.
Groups of 20 male and 20 female SPF Wistar rats were fed 0, 5, 10, 20 or 50 ppm tetraethyldithiopyrophosphate (TEDP) in the diet for 3 months. The parameters examined were body weight, food consumption, hematology, urinalysis, and plasma and RBC cholinesterase activity. At the end of the experiment, the animals were sacrificed and necropsied; internal organs were examined macroscopically and histologically. The only parameter that differed from controls was cholinesterase activity. Plasma and erythrocyte cholinesterase activity of rats fed at 20 and 50 ppm TEDP were depressed in a dose-related manner. Depression of cholinesterase activity was more pronounced in erythrocytes. Therefore, 20 ppm is the LOAEL and 10 ppm, the NOEL.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The UF of 1000 includes factors of 10 for interspecies extrapolation, 10 to extrapolate from a subchronic study and 10 to provide protection for sensitive individuals.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Kimmerle and Klimmer (1974) determined the oral LD50 of TEDP in male and female NMRI mice, Wistar rats and white Leghorn hens, and male cats, New Zealand rabbits and beagle dogs. The LD50 ranged from 3-30 mg/kg bw with the most susceptible animals being cats and dogs. The symptoms involved depression of the cholinesterase activity of the peripheral and central nervous system. Hens exposed to oral doses up to 50 mg/kg body weight did not develop any neurotoxic effects. Lehman (1952a,b) fed rats TEDP in the diet at 60 or 180 ppm for 52 weeks. The only endpoints examined were histopathology and mortality. An increase in mortality was observed at 180 ppm (9 mg/kg/day) but not 60 ppm (3 mg/kg/day). No histopathological changes were reported. Pertinent data regarding the possible teratogenicity of TEDP were not located in the available literature.
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
The subchronic oral study in rats by Kimmerle and Klimmer (1974) uses a number of dosing levels, an adequate number of rats and examines a number of endpoints, with cholinesterase inhibition as the critical endpoint. There are no supporting studies so the study is ranked medium rather than high. TEDP has not been tested for chronic toxicity or teratogenicity so confidence in the database is low. Because of the incomplete database, confidence in the RfD is low.
__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 — None
Agency Work Group Review — 02/24/1988
Verification Date — 02/24/1988
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 tetraethyldithiopyrophosphate conducted in August 2003 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 — Tetraethyldithiopyrophosphate
CASRN — 3689-24-5
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Tetraethyldithiopyrophosphate
CASRN — 3689-24-5
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Tetraethyldithiopyrophosphate
CASRN — 3689-24-5
Last Revised — 03/01/1991
_VI.A. Oral RfD References
Kimmerle, G. and O.R. Klimmer. 1974. Acute and subchronic toxicity of sulfotep. Arch. Toxicol. 33(1): 1-16.
Lehman, A.J. 1952a. Chemicals in foods: A report to the Association of Food and Drug Officials on current developments. Part II. Pesticides. Section III. Subacute and chronic toxicity. Quart. Bull. Assoc. Food Drug Officials. U.S. 16: 47-53.
Lehman, A.J. 1952b. Chemicals in foods: A report to the Association of Food and Drug Officials on current developments. Part II. Pesticides. Section V. Pathology. Quart. Bull. Assoc. Food Drug Officials. U.S. 16: 126-132.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Tetraethyldithiopyrophosphate
CASRN — 3689-24-5
Date |
Section |
Description |
---|---|---|
09/07/1988 | I.A. | Oral RfD summary on-line |
04/01/1989 | V. | Supplementary dat on-line |
03/01/1991 | VI. | Bibliography on-line |
01/01/1992 | I.A.7. | Secondary contact changed |
01/01/1992 | IV. | Regulatory Action section on-line |
02/01/1995 | I.A.7. | Secondary contact's name 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. |
10/28/2003 | I.A.6 | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Tetraethyldithiopyrophosphate
CASRN — 3689-24-5
Last Revised — 09/07/1988
- 3689-24-5
- TEDP
- Tetraethyldithiopyrophosphate