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International and U.S. guidance for developmental neurotoxicity (DNT) testing of chemicals are provided by OECD DNT test guideline 426, OECD extended one-generation reproductive toxicity study (EOGRTS) test guideline 443, and U.S. EPA DNT test guideline 870.6300. These guidelines with their multiple behavioral and neuropathology endpoints are among the most logistically complex, labor-intensive bioassays conducted for regulatory purposes. This article identifies key issues in the practical implementation and analysis of neurobehavioral and neuropathology endpoints, with emphasis on quantitative brain morphometry testing requirements. This article also reviews the development of DNT guidelines, strengths and limitations of validation efforts, regulatory triggers for DNT testing, and recent guidance from government and workgroup efforts to enhance conduct and interpretation of studies for regulatory risk assessment purposes.

Previous studies have shown that stressors attenuate LiCl-induced conditioned taste aversions (CTA) but not morphine-induced CTA. The current studies examined the effects of footshock on the acquisition and extinction of amphetamine-induced CTA. Experiment 1 demonstrated that exposure to 30 footshocks between saccharin consumption and amphetamine injections did not alter either the acquisition or the extinction of amphetamine-CTA. Experiment 2 demonstrated that exposure to the same shock parameters 2 and 4 days before saccharin-amphetamine pairing increased the magnitude of amphetamine-CTA after one saccharin-amphetamine pairing and delayed the recovery from the CTA. Experiment 2 also demonstrated that footshock increased the initial neophobic response to novel saccharin but did not alter subsequent saccharin consumption among saline-injected animals. These results indicate that stress-induced facilitation of amphetamine CTA are time-dependent and contrast with reports that stressors attenuate LiCl CTA. They also add support to the contention that CTAs induced by self-administered drugs like amphetamine are qualitatively different from CTAs induced by toxic substances like LiCL.

Studies of the morphology and chemical composition of surface-located white inorganic films are described,together with the results of artificially raising the concentration of calcium ions absorbed within the lenses on the nature of the resultant spoilation. This type of white film is structurally heterogeneous and is composed of discrete crystals of calcium phosphate-carbonate overlaid by a lipid-rich organic layer, which is not chemically bound to the deposited inorganic layer, but shows elevated cholesterol ester levels consistent with an enhanced lid involvement with the rugous surface film. Elevated calcium levels within the lens matrix were found not to accelerate the rate of formation of conventional ‘white spot’ deposition.