Environmental Profiles of Chemical Flame-Retardant Alternatives for

Immunotoxicity (OPPTS Harmonized Guideline 870.7800)
Critical study
Type: Immunotoxicity, subcutaneous, acute
Species, strain, sex, number: Mouse, B6C3F 1, 6-8 females/dose
Doses: 0, 0.25, 2.5, or 25 mg/kg/day (Total cumulative doses of 0, 1, 10, or 100 mg/kg)
Identity: [Formulation 2]; this is the same as Proprietary A tested in the 2-year oral assay by
Ref. 24
Purity: purity >95%
Vehicle: Corn oil
Route: Subcutaneous injection
Exposure duration, frequency: 4 days, once daily
Method: Observations included body weight, hematology, clinical chemistry (5 parameters)
terminal necropsy, organ weights (liver, spleen and thymus), histopathology of spleen, thymus,
and eight other organs, plaque-forming assay response to sheep red blood cells, and serum
immunoglobulin quantification (non-immunized mice only). Non-guideline tests included
proliferative capacity of granulocyte-macrophage progenitor cells (bone marrow), in vitro
lymphoproliferative (LP) responses to mitogens, delayed hypersensitivity response to keyhole
limpet hemocyanin. Extensive statistical analysis.
Results: Twenty percent of high-dose mice exhibited lymphoid depletion of the thymus.
Statistically significant decreases in vitro lipopolysaccharide (B-cell antigen) at 2.5 mg/kg/day
and concanavalin A (T-cell antigen) at 25 mg/kg/day.
Reference: Ref. 35
GENOTOXICITY
Conclusion:
The available genotoxicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
Proprietary A has been tested in in vitro and in vivo genotoxicity assays conducted in prokaryotic
and eukaryotic cells under methods similar to guidelines. Results of in vivo tests (mutation in
Drosophila, chromosomal aberration in mice) were negative, but positive results were reported
in several in vitro assays (mutagenicity in bacterial and mammalian cells, chromosomal
aberration).
Gene Mutation in Vitro:
C
Bacterial Reverse Mutation test (OPPTS Harmonized Guideline 870.5100; OECD
Guideline 471)
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