Merphos oxide (CASRN 78-48-8)
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0367
Merphos oxide; CASRN 78-48-8
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 Merphos oxide
File First On-Line 09/07/1988
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 04/01/1991 |
Inhalation RfC Assessment (I.B.) | message | 11/01/1992 |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Merphos oxide
CASRN — 78-48-8
Last Revised — 04/01/1991
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
|
---|---|---|---|---|
Ataxia, delayed 90-Day Hen Delayed Abou-Donia et al., |
NOEL: 0.1 mg/kg/day LOAEL: 0.5 mg/kg/day |
3000
|
1
|
3E-5
mg/kg/day |
*Conversion Factors: None
__I.A.2. Principal and Supporting Studies (Oral RfD)
Abou-Donia, M.B., D.G. Graham, K.M. Abdo and A.A. Komeil. 1979. Delayed neurotoxic, late acute and cholinergic effects of S,S,S- tributylphosphorotrithioate (DEF): Subchronic (90 days) administration in hens. Toxicology. 14: 229-243.
Groups of mixed breed hens (5/group) were given a daily oral dose of either 0.1, 0.5, 1.0, 2.5, 5.0, 10, 20, 40 or 80 mg/kg of merphos oxide in gelatin capsules for 3 months. Hens at the highest two doses were given 10 to 30 mg/kg/day atropine sulfate (4 to 7 days) as protection against cholinergic effects. Controls consisted of four groups of five hens treated orally with either empty gelatin capsules; 10 mg/kg/day tri-o-cresyl phosphate (positive control); or 1 mg/kg/day parathion (negative control) for 3 months. Another group of three hens was given a daily oral dose of 30 mg/kg of atropine sulfate for 34 to 90 days as an atropine sulfate control. At the end of the treatment period, the birds were observed for 1 month then sacrificed and tissues were taken from the central and peripheral nervous systems for histological examination. Hens receiving 20-80 mg/kg/day lost weight and developed severe ataxia and delayed neurotoxicity that progressed to paralysis. Mortality also occurred at these dose levels. Hens receiving doses of 0.5 to 10 mg/kg/day lost weight, but regained it by the end of the observation period. These hens also showed mild to gross ataxia, and equivocal or negative histopathological changes in the spinal cord and peripheral nerves.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 3000 was used for inter- and intraspecies extrapolation, subchronic to chronic duration and an incomplete database.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD
1) 90-Day Oral - hen: Principal study, see previous description; no core grade (Abou-Donia et al., 1979)
2) 2-Year Feeding - rat: NOEL=0.25 mg/kg/day; LEL=1.25 mg/kg/day (brain ChE inhibition); (Mobay Chemical Corp., 1969)
3) 2-Year Feeding - dog: ChE NOEL=0.12 mg/kg/day; Systemic NOEL=1.25 mg/kg/day (Mobay Chemical Corp., 1967a)
4) 2-Year Feeding - rat: ChE NOEL=0.25 mg/kg/day; Systemic NOEL=1.25 mg/kg/day; LEL=5 mg/kg/day (fatty change in liver) (Mobay Chemical Corp., 1967b)
5) 16-Week Feeding - rat: ChE NOEL=0.5 mg/kg/day; Systemic NOEL=0.5 mg/kg/day; LEL = 2.5 mg/kg/day (liver and kidney changes) (Mobay Chemical Corp., 1965a)
6) 12-Week Feeding - dog: ChE NOEL=none; ChE LEL=0.12 mg/kg/day; Systemic NOEL=0.12 mg/kg/day; Systemic LEL=0.62 mg/kg/day (oversensitive to stimuli) (Mobay Chemical Corp., 1965b)
7) 3-Generation Reproduction - mouse: Reproductive NOEL=100 ppm (13 mg/kg/day) (Mobay Chemical Corp., 1967c)
Data Gaps: None
__I.A.5. Confidence in the Oral RfD
Study — Low
Database — Low
RfD — Low
Low confidence rating to the critical study is due to design deficiencies. Supporting data are too limited to merit a confidence greater than low. Low confidence in the RfD follows.
__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 Files.
Agency Work Group Review — 11/21/1985, 08/13/1987
Verification Date — 08/13/1987
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 Merphos oxide 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 — Merphos oxide
CASRN — 78-48-8
The health effects data for Merphos Oxide (orthophosphate defoliant) have been reviewed by the U.S. EPA RfD/RfC Work Group and determined to be inadequate for derivation of an inhalation RfC. The verification status of this chemical is currently not verifiable. This assessment is not presented in any existing EPA document.
Agency Work Group Review — 06/25/1992
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfC for Merphos oxide conducted in September 2002 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.
EPA Contacts:
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).
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Merphos oxide
CASRN — 78-48-8
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 — Merphos oxide
CASRN — 78-48-8
Last Revised — 11/01/1992
_VI.A. Oral RfD References
Abou-Donia, M.B., D.G. Graham, K.M. Abdo and A.A. Komeil. 1979. Delayed neurotoxic, late acute and cholinergic effects of S,S,S-tributyl phosphoro- trithioate (DEF): Subchronic (90 days) administration in hens. Toxicology. 14: 229-243.
Mobay Chemical Corporation. 1965a. MRID No. 00087423. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Mobay Chemical Corporation. 1965b. MRID No. 00087421. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Mobay Chemical Corporation. 1967a. MRID No. 00087428. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Mobay Chemical Corporation. 1967b. MRID No. 00145268, 00145868. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Mobay Chemical Corporation. 1967c. MRID No. 00087427, 00144939. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Mobay Chemical Corporation. 1969. MRID No. 00087426. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
_VI.B. Inhalation RfC References
None available
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Merphos oxide
CASRN — 78-48-8
Date |
Section |
Description |
---|---|---|
09/07/1988 | I.A. | Oral RfD summary on-line |
04/01/1991 | I.A. | Text edited |
04/01/1991 | I.A.4. | Citations added |
04/01/1991 | VI. | Bibliography on-line |
08/01/1992 | I.B. | Inhalation RfC now under review |
11/01/1992 | I.B. | Not verified; data inadequate |
11/01/1992 | VI.B. | No references available |
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., I.B. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Merphos oxide
CASRN — 78-48-8
Last Revised — 09/07/1988
- 78-48-8
- B-1,776
- butifos
- butiphos
- butyl phosphorotrithioate
- Chemagro 1,776
- DEF defoliant
- DE-green
- E-Z-Off D
- Fos-Fall
- Merphos Oxide
- Ortho phosphate defoliant
- phosphorotrithioic acid, S,S,S-tributyl ester
- S,S,S-tributyl phosphorotrithioate
- S,S,S-tributyltrithiofosfat
- S,S,S-tributyl trithiophosphate