Norflurazon (CASRN 27314-13-2)
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0082
Norflurazon;
CASRN 27314-13-2
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 Norflurazon
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 04/01/1991 |
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 — Norflurazon
CASRN — 27314-13-2
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 |
---|---|---|---|---|
Liver and thyroid 6-Month Dog Feeding Sandoz-Wander, 1973 |
NOEL: 150 ppm LEL: 450 ppm |
100 |
1 |
4E-2 |
*Conversion Factors: 1 ppm = 0.025 mg/kg/day (assumed dog food consumption)
__I.A.2. Principal and Supporting Studies (Oral RfD)
Sandoz-Wander, Inc. 1973. MRID No. 00111618. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Four groups of 4 male and 4 female beagle dogs were exposed to 0, 50, 150, or 450 ppm Norflurazon in the diet for 6-months. At 450 ppm, effects were seen in the liver and the thyroid. Liver effects were increased weights, congestion, and swelling of the hepatocytes. Thyroid changes involved a slight increase in colloidal vacuoles. The NOEL for Norflurazon in this study was 150 ppm.
__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. An additional UF of 10 to account for the subchronic (6-month) duration of the dog study was not considered necessary since comparing the results of the 90-day rat study and the life time rat study does not indicate that Norflurazon exerts toxic effects at lower doses when exposure is of a chronic nature as compared to subchronic exposure.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Norflurazon has been found to be associated with an increased incidence of hepatomas in male mice at the highest dose in the chronic mouse study. The available reviews and risk assessments are included here.
Data Considered for Establishing the RfD
1) 6-Month Feeding - dog: Principal study - see discussion above; core grade minimum
2) 2-Year Feeding - rat: NOEL=375 ppm (18.75 mg/kg/day); LEL=1025 ppm (51.25 mg/kg/day) (inhibition of body weight gain; high BUN and reduced 2,3- diphosphoglyceric acid; increased mortality; increased liver, kidney, and ovary weights; fatty changes in adrenal; endometritis; increased chromophobe adenomas in the pituitary; medullary or cortical hypertrophy in adrenals; casts in kidneys); core grade minimum (Sandoz, Inc., 1975a)
3) 90-Day Feeding - rat: NOEL=500 ppm (25 mg/kg/day); LEL=2500 ppm (250 mg/kg/day) (increased liver-to-body weight ratios); no core grade (Sandoz, Inc., 1971)
4) 3-Generation Reproduction - rat: NOEL=375 ppm (18.75 mg/kg/day); LEL=1025 ppm (51.25 mg/kg/day) (reduced fertility, gestation, and viability); core grade minimum (Sandoz, Inc., 1975b)
5) Teratology - rat: NOEL (maternal, fetal, teratogenic)=400 mg/kg/day (highest dose tested); core grade minimum (Sandoz, Inc., 1972)
6) Teratology - rabbit: Maternal NOEL=30 mg/kg/day; Maternal LEL=60 mg/kg/day (decreased weight gain, 2/15 aborted); Fetotoxic NOEL=10 mg/kg/day; Fetotoxic LEL=30 mg/kg/day (decreased weight; incomplete ossification); core grade guideline (Sandoz, Inc., 1983)
Other Data Reviewed
1) 2-Year Feeding - mice: NOEL=340 ppm (50 mg/kg/day); LEL=1360 ppm (200 mg/kg/day) (increased liver/body weight ratios; hyperplasia, hypertrophy); core grade minimum (Sandoz, Inc., 1975c)
Data Gap(s): None
__I.A.5. Confidence in the Oral RfD
Study — High
Database — High
RfD — High
The principal study is of good quality and is given a high confidence rating. Additional studies are of good quality and there are no data gaps; 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 Standard, July 1984
Pesticide Registration Files
Agency Work Group Review — 07/08/1986
Verification Date — 07/08/1986
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 Norflurazon conducted in November 2001 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 — Norflurazon
CASRN — 27314-13-2
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Norflurazon
CASRN — 27314-13-2
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Norflurazon
CASRN — 27314-13-2
Last Revised — 04/01/1991
_VI.A. Oral RfD References
Sandoz, Inc. 1975a. MRID No. 00082019, 00111617. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sandoz, Inc. 1971. MRID No. 00091055. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sandoz, Inc. 1975b. MRID No. 00080750, 00080751. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sandoz, Inc. 1972. MRID No. 00063621. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sandoz, Inc. 1983. MRID No. 00131152. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sandoz, Inc. 1975c. MRID No. 00041015, 00041016, 00041401, 00044336. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Sandoz-Wander, Inc. 1973. MRID No. 00111618. 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 — Norflurazon
CASRN — 27314-13-2
Date |
Section |
Description |
---|---|---|
03/31/1987 | IV. | Regulatory Action section on-line |
04/01/1991 | I.A.4. | Citations added |
04/01/1991 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory actions updated |
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 — Norflurazon
CASRN — 27314-13-2
Last Revised — 01/31/1987
- 27314-13-2
- 4-CHLORO-5-(METHYLAMINO)-2-(alpha,alpha,alpha-TRIFLUORO-m-TOLYL)-3(2H)- PYRIDAZINONE
- EVITAL
- MONOMETFLURAZONE
- Norflurazon
- 3(2H)-PYRIDAZINONE, 4-CHLORO-5-(METHYLAMINO)-2-(alpha,alpha,alpha-TRIFLUORO-m- TOLYL)-
- SAN 9789
- SAN 9789 H
- SOLICAM
- ZORIAL