Ethion (CASRN 563-12-2)
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0156
Ethion;
CASRN 563-12-2
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 Ethion
File First On-Line 03/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 09/01/1989 |
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 — Ethion
CASRN — 563-12-2
Last Revised — 09/01/1989
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
|
---|---|---|---|---|
Plasma cholinesterase Cholinesterase FMC Corp., 1970 |
NOEL: 0.05 mg/kg/day LEL: 0.075 mg/kg/day |
100
|
1
|
5E-4
mg/kg/day |
Inhibition of brain 90-Day Dog Study FMC Corp., 1988 |
NOEL: 2.5 ppm LEL: 25 ppm |
*Conversion Factors -- Actual dose tested
__I.A.2. Principal and Supporting Studies (Oral RfD)
FMC Corporation. 1970. MRID No. 00073157. FMC Corporation. 1988. MRID No. 40773301. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
A total of 10 male adult human volunteers ranging in age from 22 to 43 years and in weight from 60.4 to 118.6 kg were used in this study (FMC Corp, 1970). The volunteers were randomly divided into a control group consisting initially of four subjects and a test group consisting of six subjects. Baseline plasma and erythrocyte cholinesterase activities were determined five times during a 2-week pretreatment period. The test period was divided into four sequential dosing regimens and a recovery period as follows: 1) 0.05 mg/kg/day - 21 days; 2) 0.075 mg/kg/day - 21 days; 3) 0.10 mg/kg/day - 21 days; 4) 0.15 mg/kg/day - 3 days; and 4) Recovery - 19 days. Test material was administered in corn oil solutions at dosages. Dosages were adjusted to body weight on a weekly basis. Control subjects received capsules containing corn oil. During the course of the study, the number of subjects was reduced (1 control subject and 1 test subject).
No consistent effects on plasma or erythrocyte cholinesterase activity were observed at the 0.05 mg/kg/day dose level, the lowest dose tested. Significant reductions of plasma cholinesterase activity from pretreatment levels were observed on day 1 of the 0.075 mg/kg/day dosing regimen and throughout the course of the serially increased dosing (0.10 and 0.15 mg/kg/day) until day 7 of the recovery period. Plasma cholinesterase activity during the 0.075, 0.10, and 0.15 mg/kg/day dosing regimens was reduced to approximately 85, 76, and 69%, respectively, of the pretreatment group mean. On day 7 of the recovery period, plasma activity was 82% of the pretreatment level; activities at days 12 and 19 of the recovery period were not significantly different from pretest levels. At the dose regimen used, erythrocyte cholinesterase activity was not affected by the test material nor was there any effect seen in any of the hematologic parameters measured during the study. Therefore, based on the plasma cholinesterase inhibition observed at 0.075 mg/kg/day, the NOEL for this study is 0.05 mg/kg/day.
Groups of beagle dogs (4/sex/dose) received ethion orally at dietary concentrations of 0, 0.5, 2.5, 25.0, and 300 ppm for 90 days (FMC Corp., 1988). The average compound intake for various groups were 0.01, 0.06, 0.71, and 6.9 mg/kg/day for males and 0.012, 0.07, 0.71, and 8.25 mg/kg/day for females.
Animals receiving 300 ppm showed signs of ataxia, emesis, miosis, and tremors. Male and female dogs of the 300 ppm group also showed a decrease in body weight and food consumption relative to the controls. Clinical chemistry indicated that ethion significantly inhibited brain and erythrocyte cholinesterase activity in males and females receiving 25 and 300 ppm. Thus, the NOEL for these endpoints is 2.5 ppm (0.06 or 0.07 mg/kg/day for males and females, respectively); the LEL=25 ppm. Plasma cholinesterase activity was inhibited in males and females receiving 2.5, 25, and 300 ppm. The decrease in plasma cholinesterase activity was dose-related. No compound-related histomorphologic changes were found in the ethion treated animals. The LEL for plasma cholinesterase activity is 2.5 ppm (0.06 mg/kg/day males; 0.07 mg/kg/day females); the NOEL is 0.5 ppm (0.01 mg/kg/day males; 0.012 mg/kg/day females).
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 10 was used to account for the differences in sensitivity within the human population. An additional UF of 10 was used to account for the brain cholinesterase inhibition observed at 25 ppm (0.71 mg/kg/day) in the subchronic dog study. An additional UF of 10 for subchronic to chronic extrapolation in the dog study was not used since there is no change in the endpoint over time.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD
1) Cholinesterase Inhibition - human: Principal study - see previous description; core grade supplementary
2) 90-Day Feeding - dog: Principal study - see previous description; core grade minimum
3) 2-Year Feeding (oncogenic) - rat: Systemic NOEL=4 ppm (0.2 mg/kg/day); Systemic LEL=40 ppm (2 mg/kg/day) (HDT; depressed plasma ChE); core grade minimum (FMC Corp., 1985a)
4) 3-Generation Reproduction - rat: NOEL=4 ppm (0.2 mg/kg/day); LEL=25 ppm (1.25 mg/kg/day) (HDT; significant plasma ChE inhibition in females); Reproductive NOEL=25 ppm (1.25 mg/kg/day) (HDT); Reproductive LEL=none; core grade minimum (FMC Corp., 1985b)
5) Teratology - rat: Developmental NOEL=0.6 mg/kg/day; Developmental LEL=2.5 mg/kg/day (sites of delayed ossification of pubes); Maternal NOEL=0.6 mg/kg/day; Maternal LEL=2.5 mg/kg/day (increased incidence of hyperactivity); core grade minimum (FMC Corp., 1983a)
6) Teratology - rabbit: Maternal NOEL=0.6 mg/kg/day; Maternal LEL=2.4 mg/kg/day (increased incidence of orange-colored urine and reduced body weight gain in females); Developmental NOEL=2.4 mg/kg/day; Developmental LEL=9.6 mg/kg/day (HDT; increased incidence of fused sternal centers); core grade minimum (FMC Corp., 1983b)
Other Data Reviewed:
1) Chronic Feeding (oncogenic) - mouse: NOEL=1.5 ppm (0.225 mg/kg/day); LEL=8 ppm (1.2 mg/kg/day) (HDT; plasma ChE inhibition); core grade minimum (FMC Corp., 1985c)
2) 2-Year Feeding - dog: Plasma ChE NOEL=6 ppm (0.15 mg/kg/day); Plasma ChE LEL=20 ppm (0.5 mg/kg/day) (depression of plasma ChE in females); Chronic NOEL not established due to study deficiencies; control hematology, serum chemistry and urinalysis data missing; core grade supplementary (FMC Corp., 1972)
3) 90-Day Feeding - rat: ChE NOEL=3 ppm (0.15 mg/kg/day); ChE LEL=10 ppm (0.5 mg/kg/day) (decreased plasma ChE activity); Brain and red blood cell cholinesterase activity was reduced at 30 and 100 ppm (1.5 and 5 mg/kg/day); core grade supplementary (FMC Corp., 1958a)
4) 90-Day Feeding - dog: ChE NOEL=1 ppm (0.025 mg/kg/day); ChE LEL=3 ppm (0.75 mg/kg/day) (reduced plasma ChE activity); no core grade (FMC Corp., 1958b)
5) Acute Delayed Neurotoxicity - hen: Acute oral LD50 is 2792 mg/kg/day and did not produce clinical or histopathological signs of neurotoxicity; core grade minimum (FMC Corp., 1986)
Data Gap(s): Chronic Dog Feeding Study
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
The critical study is of adequate quality and is given a medium confidence rating. Since the 2-year dog study does not satisfy the data requirement for a chronic oral toxicity study in a non-rodent species, the database is given a medium confidence rating. Medium confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Standard, February 1989
Pesticide Registration File
Agency Work Group Review — 09/16/1986, 05/17/1989
Verification Date — 05/17/1989
__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 — Ethion
CASRN — 563-12-2
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Ethion
CASRN — 563-12-2
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 — Ethion
CASRN — 563-12-2
Last Revised — 09/01/1989
_VI.A. Oral RfD References
FMC Corporation. 1970. MRID No. 00073157. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1988. MRID No. 40773301. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1985a. MRID No. 00148991. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1985b. MRID No. 00148990. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1983a. MRID No. 00131852. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1983b. MRID No. 00131853. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1985c. MRID No. 00148989. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1972. MRID No. 00141845. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1958a. MRID No. 00073077. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1958b. MRID No. 00073708. Available from EPA. Write to FOI, EPA, Washington DC 20460.
FMC Corporation. 1986. MRID No. 00158376. 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 — Ethion
CASRN — 563-12-2
Date |
Section |
Description |
---|---|---|
02/01/1989 | I.A. | Critical study citation year added |
06/01/1989 | I.A. | Withdrawn; new Oral RfD verified (in preparation) |
09/01/1989 | I.A. | Oral RfD summary on-line; RfD changed |
09/01/1989 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory Action section on-line |
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. |
02/22/2001 | I.A., II. | This chemical is being reassessed under the IRIS Program. |
02/09/2004 | I.A., II. | This chemical is no longer being reassessed under the IRIS Program. See Federal Register February 9, 2004 (Volume 69, Number 26). |
_VIII. Synonyms
Substance Name — Ethion
CASRN — 563-12-2
Last Revised — 03/31/1987
- 563-12-2
- AC 3422
- Bis(S-(Diethoxyphosphinothioyl)Mercapto)Methane
- Bladan
- Diethion
- Embathion
- ENT 24,105
- Ethanox
- Ethiol
- Ethiol 100
- Ethion
- Ethodan
- Ethopaz
- Ethyl Methylene Phosphorodithioate
- FMC-1240
- Fosfatox E
- Fosfono 50
- Hylemax
- Hylemox
- Itopaz
- KWIT
- NIA 1240
- Niagara 1240
- Nialate
- O,O,O,O-Tetraethyl S,S'-Methylenebis
- O,O,O',O'-Tetraethyl S,S'-Methylenebisphosphordithioate
- O,O,O',O'-Tetraethyl S,S'-Methylenebisphos-phorodithioate
- O,O,O',O'- Tetraethyl S,S'-Methylene Di(Phosphorodithioate)
- Phosphorodithioic Acid, S,S'-Methylene O,O,O',O'-Tetraethyl Ester
- Phosphotox E
- Rhodiacide
- Rhodocide
- Rodocid
- Rodocide
- RP 8167
- Soprathion
- S,S'-Methylene O,O,O',O'-Tetraethyl Phosphorodithioate
- Tetraethyl S,S'-Methylene Bis(Phosphorothiolothionate)
- Vegfru Fosmite