Environmental Profiles of Chemical Flame-Retardant Alternatives for

Conclusion:
The available subchronic oral toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
A Japanese 90-day dietary study in mice (Ref. 30) provides limited relevant information in the
English abstract and data tables. The study was not adequate to characterize this endpoint
because histopathological analysis was apparently limited to the liver. A fertility study by Ref.
62, discussed under the Reproductive Toxicity endpoint, evaluated male rabbits exposed by oral
gavage for 12 weeks, but did not involve treated females.
• Repeated Dose 28-Day Oral Toxicity in Rodents (OPPTS Harmonized Guideline
870.3050; OECD Guideline 407)
No study of this type was located.
90-Day Oral Toxicity in Rodents (OPPTS Harmonized Guideline 870.3100; OECD
Guideline 408)
Type: 90-Day repeated oral
Species, strain, sex, number: Mouse, Slc/ddY, 12/sex/dose
Doses: Proprietary A at dietary concentrations of 0, 0.01, 0.04, 0.13, 0.42, and 1.33% in the diet,
resulting in reported average daily doses of 0, 13.2, 47.3, 171.0, 576.0, and 1,792.3 mg/kg/day in
males and 0, 15.3, 62.5, 213.6, 598.0, and 1,973.1 mg/kg/day in female mice
Purity: Not reported
Vehicle: None; added to diet
Exposure period, frequency: 90 days, ad lib
Method: Body weight, food consumption measured weekly. At 1 and 3 months in half the
animals, hematologic (erythrocyte, hemoglobin, hematocrit, and leukocyte counts) and clinical
chemistry parameters (total protein, albumin, albumin/globulin ratio, blood urea nitrogen,
glucose, total cholesterol, alkaline phosphatase, aspartate aminotransferase, alanine
aminotransferase). At 1 and 3 months, half the animals were necropsied and absolute and
relative organ weights were determined for brain, heart, lung, liver, kidney, and spleen. The
liver was examined for microscopic histopathology; the English text does not mention whether
other tissues were examined.
Results: At the highest dietary level, 1.33%, all mice exhibited emaciation, rough hair, and
tremor and died within 1 month. At 1.33%, food consumption was reduced and body weight loss
occurred in both sexes. Mean body weight gain was reduced by about 10% (estimated from
graph) in males at 0.42% throughout the study. The following statistically significant changes
occurred in treated groups compared to controls. Slight anemia (reduced hemoglobin; p