Environmental Profiles of Chemical Flame-Retardant Alternatives for

• 90-Day Oral Toxicity in Rodents (OPPTS Harmonized Guideline 870.3100; OECD
Guideline 408)
The only $90 day subchronic studies of TPP toxicity were specialized studies of reproductive,
developmental, neurological, and immunological endpoints in the rat conducted by the FDA
(Hinton et al., 1987; Sobotka et al., 1986; Welsh et al., 1987). These studies provide only
limited information on other systemic toxicities, and therefore do not satisfy the guideline.
• In the reproductive and developmental toxicity study in the rat, males and females were
fed TPP at dietary levels up to 1% for 91 days prior to mating, continuing through
mating, and the females were continued on the diet until day 20 of gestation. This study
reported no differences in behavior or gross pathology of the treated dams, a slight but
significant decrease on day 0 of gestation in the body weight of the dams fed the 1% diets
(690 mg/kg/day), a slight but significant increase in food consumption primarily at 0.5
and 0.75% in the diet(not dose-related), and a non-significant decrease in body weight
gain (minus the gravid uterus) at day 20 of gestation in dams fed $0.5% (341 mg/kg/day)
(Welsh et al., 1987).
• The neurological study, in which male rats were fed up to 1% TPP in the diet for 4
months, provided no evidence of neurobehavioral effects, but also noted a decrease in
body weight gain. The NOAEL and LOAEL for this effect were 0.25% in the diet (161
mg/kg/day) and 0.50% in the diet (345 mg/kg/day) (Sobotka et al., 1986).
• In the immunotoxicity study, in which male and female rats were fed up to 1% TPP in the
diet for 4 months, the only effects seen were a decrease in body weight gain at 1.0%
(approximately 700 mg/kg/day) in the diet, and non-dose related increases in the relative
percentages of "-globulins in treated females and $-globulins in treated males, which
were interpreted as a possible sign of liver activity of uncertain toxicological significance
(Hinton et al., 1987). Because of the lack of dose-response, these findings may not be
indicative of a chemical effect. The NOAEL and LOAEL for decreased body weight
gain were 0.75% in the diet (517 mg/kg/day) and 1.0% in the diet (700 mg/kg/day).
Details of these studies are provided in the appropriate sections. These studies are not adequate
to fulfill the requirements of the 90-day subchronic oral toxicity guideline.
An associated, concurrent FDA subchronic toxicity study, mentioned in the other FDA reports
(Hinton et al., 1987, 1996; Sobotka et al., 1986; Welsh et al., 1987), has not been published. The
study has been requested for review.
• Combined Repeated Dose Toxicity Study with the Reproduction/Developmental
Toxicity Screening Test (OPPTS Harmonized Guideline 870.3650; OECD Guideline
422)
No studies of this type were located.
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