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Environmental Profiles of Chemical Flame-Retardant Alternatives for

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Basis <strong>for</strong> Conclusion:<br />

The only study evaluating the potential immunotoxicity <strong>of</strong> TDCPP (Luster et al., 1981) predates<br />

the guideline <strong>for</strong> immunotoxicity (note that the OPPTS guideline cites other works by this<br />

author). There is some uncertainty as the test material, reported as Fyrol FR2, but mis-identified<br />

by the authors as tris(2,3-dichloropropyl) phosphate. The study methods differed from the<br />

guideline in the short exposure period (4 rather than 28 days), parenteral administration (rather<br />

than oral or inhalation route), measurement <strong>of</strong> serum immunoglobulins in non-immunized rather<br />

than immunized mice, and the omission <strong>of</strong> some tests (enumeration <strong>of</strong> immunological cell<br />

subpopulations, test <strong>for</strong> NK-cell activity). The results do not provide dose–response in<strong>for</strong>mation<br />

as to immunotoxicity <strong>of</strong> TDCPP following subchronic exposure by oral or inhalation routes <strong>of</strong><br />

exposure.<br />

Immunotoxicity (OPPTS Harmonized Guideline 870.7800)<br />

Critical study<br />

Type: Immunotoxicity, subcutaneous, acute<br />

Species, strain, sex, number: Mouse, B6C3F 1, 6-8 females/dose<br />

Doses: 0, 0.25, 2.5, or 25 mg/kg/day (Total cumulative doses <strong>of</strong> 0, 1, 10, or 100 mg/kg)<br />

Identity: Stauffer Fyrol FR-2, lot 4670-3-23. This is the same lot as TDCPP tested in the 2-year<br />

oral assay by Freudenthal and Henrich (2000)<br />

Purity: Stauffer, purity >95%<br />

Vehicle: Corn oil<br />

Route: Subcutaneous injection<br />

Exposure duration, frequency: 4 days, once daily<br />

Method: Observations included body weight, hematology, clinical chemistry (5 parameters)<br />

terminal necropsy, organ weights (liver, spleen and thymus), histopathology <strong>of</strong> spleen, thymus,<br />

and eight other organs, plaque-<strong>for</strong>ming assay response to sheep red blood cells, and serum<br />

immunoglobulin quantification (non-immunized mice only). Non-guideline tests included<br />

proliferative capacity <strong>of</strong> granulocyte-macrophage progenitor cells (bone marrow), in vitro<br />

lymphoproliferative (LP) responses to mitogens, delayed hypersensitivity response to keyhole<br />

limpet hemocyanin. Extensive statistical analysis.<br />

Results: Twenty percent <strong>of</strong> high-dose mice exhibited lymphoid depletion <strong>of</strong> the thymus.<br />

Statistically significant decreases in vitro lipopolysaccharide (B-cell antigen) at 2.5 mg/kg/day<br />

and concanavalin A (T-cell antigen) at 25 mg/kg/day.<br />

Reference: Luster et al., 1981<br />

GENOTOXICITY<br />

Conclusion: The available genotoxicity data were judged adequate to meet the endpoint.<br />

3-22

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