Environmental Profiles of Chemical Flame-Retardant Alternatives for

Species, strain, sex, number: Rat, Sprague-Dawley, 10 males and 10 females/dose
Doses: 0. 0.25, 0.50, 0.75, or 1.00% TPP in the diet; approximately equivalent (based on
measured dosages in the related studies by Sobotka et al., 1986 and Welsh et al., 1987) to 0, 163,
343, 517, and 700 mg/kg/day. No positive control.
Purity: Aldich, 98% pure, confirmed by gas chromatography, stable under the experimental
conditions of this study
Exposure duration, frequency: 120 days, daily
Method: Observations included body weight, food consumption, midterm and terminal sacrifice,
necropsy, spleen and thymus weights, histopathology of spleen, thymus, and mesenteric lymph
nodes, immunohistochemical evaluation of B- and T-lymphocyte regions in these tissues, total
serum protein and electrophoretic analysis of serum proteins, humoral response to sheep red
blood cells (relative antibody titers by hemolytic assay). Extensive statistical analysis.
Results: The only statistically significant effects were a decreased growth rate (>10% difference
in body weight) during the first 4 weeks in males and females of the 1.00% dietary group, and
non-dose related increases in the relative percentages of "-globulins in treated females and $globulins
in treated males, which were interpreted by the study authors as a possible sign of liver
activity but of uncertain toxicological significance. Because of the lack of dose-response, these
findings may not be indicative of a chemical effect. This study did not demonstrate a LOAEL
for immunotoxicity. 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).
Reference: Hinton et al., 1987
GENOTOXICITY
Conclusion: The available genotoxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
Three studies of gene mutation in vitro report negative results. These studies, two in bacteria
and one in mammalian cells, predate the relevant guidelines, but were conducted in a manner
similar to them, and together, characterize the gene mutation in vitro endpoint. Studies of
chromosomal aberrations were not available, however, and are needed for adequate
characterization of the genotoxicity endpoint.
Gene Mutation in Vitro:
• Bacterial Reverse Mutation test (OPPTS Harmonized Guideline 870.5100;
OECD Guideline 471)
Type: Bacterial reverse mutation
Species, strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537
Metabolic activation: Tested with and without Aroclor 1254-induced liver S9 from male Syrian
hamsters (10% in S9 mix for all strains and also 50% for TA1535 and TA1537), and male
Sprague-Dawley rats (10% for all strains)
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