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U.S. EPA IRIS Substance rile-Norflurazon:CASRN 27314-13-2 http://www.epa.gov/ngispgm3/iris/subst/0082.htm 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 _LA.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD) OF -- An uncertainty factor of 100 was used to account for the inter- and intraspecies differences. An additional OF 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 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) of 7 5/15,100 11:14 AM