Oral gavage subchronic neurotoxicity and inhalation subchronic immunotoxicity studies of ethylbenzene in the rat.

The potential for neurotoxicological and immunotoxicological effects of ethylbenzene was studied in young adult Crl:CD(SD) rats following 90-day oral (neurotoxicity) or 28-day inhalation (immunotoxicity) exposures. In the neurotoxicity study, ethylbenzene was administered orally via gavage twice daily at 0, 25, 125, or 250 mg/kg per dose (total daily dosages of 0, 50, 250, or 500 mg/kg bwt/day [mg/kg bwt/day]) for 13 weeks and the functional observational battery (FOB), automated tests for motor activity and neuropathological examination were conducted. In the immunotoxicity study, animals were exposed by inhalation to 0, 25, 100, or 500 ppm ethylbenzene (approximately 26, 90, or 342 mg/kg bwt/day as calculated from physiologically based pharmacokinetic modeling).

Statistical issues and techniques appropriate for developmental neurotoxicity testing: a report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints.

The data from developmental neurotoxicity (DNT) guideline studies present a number of challenges for statistical design and analysis. The importance of specifying the planned statistical analyses a priori cannot be overestimated. A review of datasets submitted to the US Environmental Protection Agency revealed several inadequate approaches, including issues of Type I error control, power considerations, and ignoring gender, time, and litter allocation as factors in the analyses.

Effects of intensity and type of prepulse stimulus on prepulse inhibition in scopolamine treated rats.

Prepulse inhibition (PPI) of the auditory startle response (ASR) is a behavioral test that has been used to measure auditory thresholds, to assess sensory-motor integration functions, and its use has been recommended in the United States Environmental Protection Agency Developmental Neurotoxicity Guideline (OPPTS 870.6300). The purpose of the present study was to determine to what extent the intensity and/or type of prepulse stimuli modulate PPI in scopolamine-treated rats.

Differential sensitivity of blood, peripheral, and central cholinesterases in beagle dogs following dietary exposure to chlorpyrifos.

Two studies were performed to find out whether exposure limits that protect brain acetylcholinesterase (AChE) will protect peripheral tissue AChE after exposure to chlorpyrifos (CPF), an organophosphate insecticide. In a methods-development study, male dogs (3/dose) were exposed to 0.0, 0.

Validation of an auditory startle response system using chemicals or parametric modulation as positive controls.

Neurotoxicity regulatory guidelines mandate that automated test systems be validated using chemicals. However, in some cases, chemicals may not necessarily be needed to prove test system validity. To examine this issue, two independent experiments were conducted to validate an automated auditory startle response (ASR) system.

Factors affecting grip strength testing.

The rodent grip strength test was developed decades ago and is a putative measure of muscular strength. This test has been included in the functional observational battery (FOB) to screen for neurobehavioral toxicity, and changes in grip strength have been interpreted as evidence of motor neurotoxicity. Despite its widespread use, questions remain about what the grip strength test actually measures.