Environmental Profiles of Chemical Flame-Retardant Alternatives for

NEUROTOXICITY
Conclusion:
The available neurotoxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
The delayed neurotoxicity component is satisfied by the existing data, but a developmental
toxicity study by Tanaka et al. (1981) that included postnatal behavioral examinations did not
fully satisfy the developmental neurotoxicity component. TDCPP gave negative results in single
acute and subchronic oral delayed neurotoxicity studies in hens and in limited postnatal testing
in rats exposed during gestation. A 2-year feeding bioassay in rats by Freudenthal and Henrich,
2000; Bio/Dynamics, 1980), discussed above under the Chronic Toxicity and Carcinogenicity
endpoints, reported no lesions of the cervical spinal cord, but a slight (not statistically
significant) increase in the incidence of gliomas of the brain in rats exposed to TDCPP at 80
mg/kg/day. The study authors could not determine whether this effect was related to exposure.
Delayed Neurotoxicity
Conclusion:
The available delayed neurotoxicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
Several acute studies and one subchronic study for delayed neurotoxicity in the hen, summarized
below, give no evidence of acute cholinergic toxicity, inhibition of neurotoxic esterase (NTE)
activity, or delayed neurotoxicity for TDCPP. These studies, performed prior to the existence of
the guidelines, do not entirely conform to current guidelines, and may lack detail such as the
purity of the TDCPP sample. The lack of significant NTE inhibition following dosing with
10,000 mg/kg suggests that no additional testing for delayed neurotoxicity is needed for TDCPP.
• Acute and 28-Day Delayed Neurotoxicity of Organophosphorus Substances (OPPTS
Harmonized Guideline 870.6100; OECD Guideline 418, 419)
Unpublished industrial acute (1- or 5-day) and subchronic (90-day) delayed neurotoxicity assays,
which pre-date the guideline, are missing some details. One acute study employed a gavage dose
5 times higher than now specified under the guideline. The subchronic assay had a longer
duration and a larger group size than specified under the guideline.
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