Submitter name: Fragrance Materials Association

Submission date: 5/22/1997

Was the submission provided under the Compliance Audit Program (CAP)?

• No

Chemical testing

Human health effects

Initial submission

No

REPRODUCTIVE TOXICITY:

• Study Type
  • Prenatal development developmental toxicity study

• Protocol/guideline
  • Other: Not reported

• Year Study Performed Not reported

• Was the Study
  • Measured

• Duration of Study 20 days

• Species
  • Rat

• Strain Sprague-Dawley

• Sex of Organisms
  • Female

• Number of Organisms per Group 25

• Test Substance Purity Not reported

• Dose/Concentrations 0 (vehicle), 50, 150, and 500 mg/kg/day

• Dose Frequency Daily

• Exposure period 11 days (GD 7-17)

• Route
  • Oral

• Results based on critical effect Pregnancy occurred in 25, 24, 24, and 21 females in the 0 (control), 50, 150, and 500 mg/kg/day dose groups, respectively. No differences in litter averages for corpora lutea, implantations, litter size, live/dead fetuses, early/late resorptions, percent resorbed conceptuses, or percent male fetuses were noted in any dose group.

• Study Results No reproductive effects were reported

DEVELOPMENTAL TOXICITY:

• Study Type
  • Other: Prenatal developmental toxicity study

• Protocol/guideline
  • Other: Not reported

• Good Lab Practices
  • Yes

• Year Study Performed Not reported

• Was the Study
  • Measured

• Duration of Study 20 days

• Species
  • Rat

• Strain Sprague-Dawley

• Sex of Organisms
  • Female

• Number of Organisms per Group 25

• Test Substance Purity Not reported

• Dose/Concentrations 0 (vehicle), 50, 150, and 500 mg/kg/day

• Dose Frequency Daily

• Exposure period 11 days (GD 7-17)

• Route
  • Oral

• Results based on critical effect In a developmental toxicity study, four groups of 25 female Sprague-Dawley rats were exposed via oral gavage to a vehicle control (corn oil) or the test substance at concentrations of 0, 50, 150 and 500 mg/kg/day on gestation days (GDs) 7 through 17. No maternal or fetal mortalities occurred during the study. Maternal clinical signs consisted of excess salivation, urine-stained abdominal fur, red or brown substance on the forepaws, and alopecia in 4-9 rats at 500 mg/kg/day. Reduced maternal body weight gains and food consumption for the entire study period were noted in rats in the 150 and 500 mg/kg/day groups. Pregnancy occurred in 25, 24, 24, and 21 females in the 0 (control), 50, 150, and 500 mg/kg/day dose groups, respectively. Fetal weights were reduced in the 500 mg/kg/day group. No differences in litter averages for corpora lutea, implantations, litter size, live/dead fetuses, early/late resorptions, percent resorbed conceptuses, or percent male fetuses were noted in any dose group. Malformations occurred in 1, 0, 2, and 6 fetuses from 1, 0, 2, and 5 litters in the four respective dosage groups. Only malformations in the 500 mg/kg/day group, which included skeletal variations, were considered to be related to the test substance. Based on these results, the submission sponsor finds that the maternal NOAEL for the test substance is 50 mg/kg/day and the developmental NOAEL is 150 mg/kg/day.

• Study Results Maternal NOAEL = 50 mg/kg/day; Developmental NOAEL = 150 mg/kg/day