Rat hyperactivity by bisphenol A, but not by its derivatives, 3-hydroxybisphenol A or bisphenol A 3,4-quinone.
Toxicol Lett. 2011 Oct 30 ;206(3):300-5. Epub 2011 Aug 22. PMID: 21884766
Center for Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. firstname.lastname@example.org
Detoxification in the central nervous system is largely unknown. The mechanism of neurotoxicity of bisphenol A, a toxic environmental chemical remains obscure. We examined the effects of bisphenol A, and its derivatives, 3-hydroxybisphenol A and bisphenol A 3,4-quinone on rat behavior as possible metabolites of bisphenol A. A single intracisternal administration of bisphenol A (20μg equivalent to 87 nmol) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age. It was about 1.3 fold more active in the nocturnal phase than control rats. However, neither 3-hydroxybisphenol A nor bisphenol A 3,4-quinone at the same amount (87 nmol) increased the spontaneous motor activity. Gas chromatographic-mass spectrometric (GC-MS) analyses of the treated brain revealed that 7% of the parent chemical resided in the brain at 8 weeks of age, but its derivatives were not found. This suggested a difference in metabolic turnover of these compounds or a difference in their stabilities. We conclude that bisphenol A per se caused hyperactivity in the rat, eliminating the possibility that possible metabolic forms of bisphenol A, 3-hydroxybisphenol A and bisphenol A 3,4-quinone have the ability to elicit rat hyperactivity, probably because of longer-lasting residence of the parent compound in the brain.