Environmental Profiles of Chemical Flame-Retardant Alternatives for

NEUROTOXICITY
Conclusion:
The available neurotoxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
Some components of this endpoint—delayed neurotoxicity and neurotoxicity screening (in adult
animals)—are satisfied by the existing data, but no study of developmental neurotoxicity has
been conducted. This endpoint could be addressed in combination with the reproductive toxicity
endpoint. TPP gave negative results in several acute oral delayed neurotoxicity studies in the
hen as well as a subcutaneous study in the cat, and also in a subchronic oral neurotoxicity
screening study in the rat. Further information is provided in the following subsections.
Delayed Neurotoxicity
Conclusion:
The available delayed neurotoxicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
The available acute delayed neurotoxicity studies in the hen and in the cat (another sensitive
species), summarized below, give no evidence of acute cholinergic toxicity or of delayed
neurotoxicity. These studies, performed prior to the existence of the guidelines, do not entirely
conform to the guidelines, and lack detail including, in the hen studies, purity of the TPP sample.
Nevertheless, together they indicate a lack of delayed neurotoxicity for TPP. Neurotoxic
esterase (NTE) assays were not conducted in these studies. In a separate unpublished study,
summarized in a review of structure-activity studies, an NTE assay in brain homogenate
following a single oral dose of 700 mg/kg TPP (>99% purity) to the hen (Johnson, 1975) gave
negative results. This dose is lower than those used in the critical studies of delayed
neurotoxicity in hens but given the lack of signs and histopathological evidence for delayed
neurotoxicity, additional NTE assays do not appear necessary.
Because of the lack of signs or histopathology indicating delayed neurotoxicity in the acute
studies, 28-day studies are not required. In addition, structure-activity studies indicate that TPP
would not be expected to cause delayed neurotoxicity (Johnson, 1975).
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