Environmental Profiles of Chemical Flame-Retardant Alternatives for

Basis for Conclusion:
The delayed neurotoxicity component is satisfied by the existing data, but a developmental
toxicity study by Ref. 59 that included postnatal behavioral examinations did not fully satisfy the
developmental neurotoxicity component. Proprietary A 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 Ref. 24, 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 Proprietary A 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 Proprietary A. 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 Proprietary A 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 Proprietary A.
• 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Unpublished industrial acute (1- or 5-day) and subchronic (90-day) delayed neurotoxicity assays,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.
Critical Studies
Type: Acute oral delayed neurotoxicity
Species, strain, sex, number: Hen, White Leghorn, 4/dose
Purity: [Formulation 2], purity not reported, clear colorless liquid
Doses: 420 mg/kg (highest dose specified in protocol)
Vehicle: test substance diluted 50% in corn oil
Positive control: 90 or 120 mg/kg/day tri-ortho-tylol phosphate (TOCP)
4-18