Difenzoquat (CASRN 43222-48-6)
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0336
Difenzoquat; CASRN 43222-48-6
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 Difenzoquat
File First On-Line 08/22/1988
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 08/22/1988 |
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 — Difenzoquat
CASRN — 43222-48-6
Primary Synonym — Avenge
Last Revised — 08/22/1988
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 |
---|---|---|---|---|
Decreased body weight 2-Year Rat Feeding American Cyanamid |
NOEL: 500 ppm LEL: 2500 ppm |
300
|
1
|
8E-2
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)
American Cyanamid Company. 1975. MRID No. 00037923. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sixty young Wistar rats of each sex were used per dosage level of 100, 500, and 2500 ppm (5, 25, and 125 mg/kg/day). The 2500 ppm level was changed to 5000 ppm (250 mg/kg/day) after the 30th week. At the 2500/5000 ppm level body weight gain was depressed for both sexes at the 52, 78, and 104 week periods. The NOEL was established at the 500 ppm for this study because of the depressed body weight gain at the high dose level. This effect was not considered to be of a severe nature but rather a consistent one during a significant part of the study.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 100 was used, 10 each to account for the inter- and intraspecies differences. An additional UF of 3 was used to account for the lack of a chronic dog study.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD
1) 2-Year Feeding (oncogenic) - rat: Principal study - see previous description; no core grade
2) 90-Day Feeding - dog: Systemic NOEL=2500 ppm (62.5 mg/kg/day) (HDT); no core grade (American Cyanamid Company, 1973)
3) 3-Generation Reproduction - rat: Systemic and Reproductive NOEL=2500 ppm (125 mg/kg/day) (HDT); Fetotoxic NOEL=500 ppm (25 mg/kg/day); Fetotoxic LEL=2500 ppm (125 mg/kg/day) (HDT; decreased pups weights at birth and weanling); no core grade (American Cyanamid Company, 1974a)
4) Teratology - rat: Systemic, Reproductive, and Teratogenic NOEL=2500 ppm (125 mg/kg/day) (HDT); Systemic, Reproductive, and Teratogenic NOEL=none; no core grade (American Cyanamid Company, 1974)
Other Data Reviewed:
1) 18-Month Oncogenic - mice: Systemic NOEL=2500 ppm (375 mg/kg/day) (HDT); no core grade (American Cyanamid Company, 1975b)
Data Gap(s): Chronic Dog Feeding Study; Rabbit Teratology Study
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
The critical study is of fair quality and is given a medium to low confidence rating. A comparison of the 90-day interim sacrifice of the critical study and the 90-day dog study indicates that the dog is probably the most sensitive species; therefore, a chronic dog feeding study is necessary to fully assess the toxicity of difenzoquat. Since a chronic dog study is lacking, 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
Source Document — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — Pesticide Registration Files
Agency Work Group Review — 10/14/1987
Verification Date — 10/14/1987
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 Difenzoquat conducted in August 2003 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 — Difenzoquat
CASRN — 43222-48-6
Primary Synonym — Avenge
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Difenzoquat
CASRN — 43222-48-6
Primary Synonym — Avenge
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 — Difenzoquat
CASRN — 43222-48-6
Primary Synonym — Avenge
Last Revised — 12/01/1989
_VI.A. Oral RfD References
American Cyanamid Company. 1973. MRID No. 00037922. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1974a. MRID No. 00030578. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1974b. MRID No. 00030576. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1975a. MRID No. 00037923. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1975b. MRID No. 00036710. 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 — Difenzoquat
CASRN — 43222-48-6
Primary Synonym — Avenge
Date |
Section |
Description |
---|---|---|
08/22/1988 | I.A. | Oral RfD summary on-line |
12/01/1989 | 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. |
10/28/2003 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Difenzoquat
CASRN — 43222-48-6
Primary Synonym — Avenge
Last Revised — 08/22/1988
- 43222-48-6
- AC 84777
- Avenge
- Difenzoquat
- difenzoquat methyl sulfate
- 1,2-dimethyl-3,5-diphenyl-1-H-pyrazolium methyl sulfate
- finaven
- mataven
- 1H-pyrazolium, (1,2-dimethyl-3,5-diphenyl)-, methyl sulfate
- yeh-yan-ku