Fluridone (CASRN 59756-60-4)
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0054
Fluridone;
CASRN 59756-60-4
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 Fluridone
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 09/01/1990 |
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 — Fluridone
CASRN — 59756-60-4
Primary Synonym — Sonar
Last Revised — 09/01/1990
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 |
---|---|---|---|---|
Glomerulonephritis, 2-Year Rat Feeding Study Elanco Products, 1980a |
NOEL: 200 ppm (8 mg/kg/day) LEL: 650 ppm (25 mg/kg/day) |
100 |
1 |
8E-2 mg/kg/day |
*Conversion Factors -- Dose in mg/kg/day provided by author of study
__I.A.2. Principal and Supporting Studies (Oral RfD)
Elcanco Products Company, Division of Eli Lilly and Company. 1980a. MRID No. 00103251, 00103305. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Three studies were conducted concurrently, using Fischer rats fed the same dietary levels of Fluridone [0, 200, 650, 2000 ppm (0, 8, 25, 81 mg/kg/day)]. The first study was a 1-year feeding study (R-1126) in which 120 animals were divided into four groups of 15 animals/sex/dietary level. The other two studies were reported to be replicate 2-year oncogenic assays (Nos. R-1136 and R-1146), in which 240 animals per assay were divided into four groups of 30 animals/sex/dietary level. These three studies constitute a 2-year study with 75 animals/sex/dietary level of which 15 animals/sex/dietary level were sacrificed at 12 months. Effects observed at 650 ppm included glomerulonephritis, atrophic testes, eye keratitis, decreased body weight and organ weights.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 100 was used to account for the inter- and intraspecies differences.
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; core grade minimum
2) 1-Year Feeding - dog: Systemic NOEL=75 mg/kg/day; Systemic LEL=150 mg/kg/day (weight loss, increased liver weight and alkaline phosphatase); core grade minimum (Elanco Products, 1981)
3) 3-Generation Reproduction - rat: Teratogenic, Maternal and Fetotoxic NOEL=2000 ppm (100 mg/kg/day) (HDT); LEL=none; Pup toxic NOEL=650 ppm (32.5 mg/kg/day); Pup toxic LEL=2000 ppm (100 mg/kg/day) (pup weight); core grade minimum for reproduction, supplementary for teratology (Elanco Products, 1980b)
4) Teratology - Rat: Maternal NOEL=100 mg/kg/day; Maternal LEL=300 mg/kg/day (decreased body weight); Developmental NOEL=300 mg/kg/day; Developmental LEL=1000 mg/kg/day (decreased fetal weight, delayed ossification); Teratogenic NOEL=1000 mg/kg/day (HDT); LEL=none; core grade minimum (Elanco Products, 1986)
5) Teratology - rabbit: Teratogenic NOEL=750 mg/kg/day (HDT); Teratogenic LEL=none; Maternal NOEL=125 mg/kg/day; Maternal LEL=30 mg/kg/day (body weight, abortion); Fetal NOEL=125 mg/kg/day; Fetal LEL=300 mg/kg/day (resorptions); core grade minimum (Elanco Products, 1980c)
Other Data Reviewed:
1) 2-Year Feeding (oncogenic) - mouse: Clinical NOEL equal to or greater than the HDT (no deaths, no toxicities, no histopathological lesions); Dose- dependent, increased AP in males [NOEL=100 ppm (15 mg/kg/day)]; MTD was not used, and food consumption not determined; core grade minimum (Elanco Products, 1982)
2) 3-Month Feeding - rat: Systemic NOEL=none; LEL=166 mg/kg/day (LDT; increased liver weight); core grade minimum (Elanco Products, 1978a)
3) 3-Month Feeding - dog: Systemic NOEL=200 mg/kg/day (HDT); LEL=none; core grade minimum (Elanco Products, 1978b)
Data Gap(s): None
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — High
RfD — High
The critical study is of adequate quality and is given a medium confidence rating. Additional studies are supportive and of good quality and therefore, the database is given a high confidence rating. High confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Files
Agency Work Group Review — 11/21/1985, 01/21/1988
Verification Date — 01/21/1988
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 Fluridone 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.
__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 — Fluridone
CASRN — 59756-60-4
Primary Synonym — Sonar
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Fluridone
CASRN — 59756-60-4
Primary Synonym — Sonar
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Fluridone
CASRN — 59756-60-4
Primary Synonym — Sonar
Last Revised — 09/01/1990
_VI.A. Oral RfD References
Elcanco Products Company, Division of Eli Lilly and Company. 1978a. MRID No. 00135208. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1978b. MRID No. 0082344. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1980a. MRID No. 00103251, 00103305. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1980b. MRID No. 00103304. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1980c. MRID No. 00103302. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1981. MRID No. 00103336. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1982. MRID No. 00103252, 00103305. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Elcanco Products Company, Division of Eli Lilly and Company. 1986. MRID No. 00159963. 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 — Fluridone
CASRN — 59756-60-4
Primary Synonym — Sonar
Date |
Section |
Description |
---|---|---|
08/22/1988 | I.A. | Oral RfD summary replaced; RfD not changed |
09/01/1990 | I.A.4. | Citations added |
09/01/1990 | VI. | Bibliography 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. |
12/03/2002 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Fluridone
CASRN — 59756-60-4
Primary Synonym — Sonar
Last Revised — 01/31/1987
- 59756-60-4
- EL 171
- Fluridone
- 4(1H)-Pyridinone, 1-methyl-3-phenyl-5-(3-(trifluoromethyl)phenyl)-
- Sonar