Environmental Profiles of Chemical Flame-Retardant Alternatives for

Combined Chronic Toxicity/Carcinogenicity (OPPTS Harmonized Guideline 870.4300;
OECD Guideline 453)
The protocol of a 2-year feeding bioassay in rats was consistent with this guideline (Ref. 9, 24).
The published article focused on tumor results rather than non-neoplastic effects.
Type: Combined oral chronic toxicity and carcinogenicity assay
Species, strain, sex, number: Rat, Sprague-Dawley, 60/sex/group
Purity: 95%
Doses: 0, 5, 20, and 80 mg/kg body weight/day
Vehicle: None other than feed
Route: In feed; diets blended weekly to achieve target doses
Exposure duration, frequency: 2 years, ad lib
Method: Examined twice daily for mortality and clinical signs, weekly physical examination.
Body weights and food consumption weekly for the first 13 weeks and biweekly thereafter.
Ophthalmoscopic examinations every 6 months. Extensive hematology, clinical chemistry and
urinalysis parameters at 3, 6, 12, 18, and 24 months. Ten/sex/dose randomly chosen for
termination at 12 months; the remainder at 24 months. Gross necropsy including organ weights
(8 organs plus gonads); histopathology of more than 30 tissues in control and high-dose rats; at
low- and mid-doses, histopathology limited to liver, kidneys, testes, and adrenals. Statistical
analyses.
Results: The following changes compared to controls were statistically significant (p