A developmental test battery for neurobehavioral toxicity in rats: A preliminary analysis using monosodium glutamate calcium carrageenan, and hydroxyurea

Abstract

A test battery for evaluating developmental neurobehavioral toxicity was designed to attempt to meet both the general requirements of a sound test system, namely, comprehensiveness, usability, and sensitivity and the specific requirements promulgated by Britain, France, and Japan as part of their reproductive guidelines for new drugs. Monosodium glutamate (MSG) and calcium carrageenan (CC) were used to obtain preliminary data with this test battery using continuous dietary exposure from prior to conception through 90 days of postnatal life. Observations were made on reproduction and on the physical and behavioral development of the offspring. Three dose levels were used with each of the food additives and the data from these subjects were compared to data from normally fed (negative) controls and a positive control group exposed to 550 mg/kg of hydroxyurea on the 12th day of gestation. Differences between MSG and negative control groups were observed in swimming development, open field, active and passive avoidance testing. Effects observed in the CC groups were inconsistent and not dose related. Prenatal treatment with hydroxyurea produced delayed startle and swimming development and reduced open field rearing activity. This pattern of effects was less than expected indicating that hydroxyurea is an adequate, but not optimal, positive control manipulation. It appears that the test protocol used in this research could, with some modification, serve as a usable screening technique for developmental neurobehavioral toxicity. © 1979.