Reproductive and Neurobehavioral Effects of Ethiprole Administered to Mice in the Diet.

BACKGROUND: Few studies were found for neurobehavioral toxicity of the phenylpyrazole insecticide ethiprole in mammals. This study was designed to evaluate the reproductive and neurobehavioral effects of ethiprole exposure in mice. METHODS: Ethiprole was given in the diet to provide levels of 0 (control), 0.0003, 0.0009, and 0.0027% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. Selected reproductive and neurobehavioral parameters were measured. RESULTS: Movement time increased with a significant dose-related trend, and frequencies of mice with urination increased in the high-dose group of adult males in the F0 generation. The average body weight of male and female offspring increased significantly in treatment groups at postnatal days (PNDs) 7, 14, and 21. Surface righting on PND 7 of male offspring was accelerated in a significant dose-related trend. In female offspring, olfactory orientation on PND 14 was accelerated significantly on the route of higher-dose groups, and time of all treatment groups. Total distance, movement time, average speed, and average time of movement significantly decreased, and frequencies of mice with urination increased in a significant dose-related trend in male offspring in the F1 generation. Longitudinal patterns of spontaneous behavior differed in the number of horizontal activities, movement time, and average speed in treatment groups in males. The number of horizontal activities of females decreased in a significant dose-related trend through 120 min. CONCLUSION: The dose levels of ethiprole in the present study produced several adverse effects in neurobehavioral parameters in mice. Birth Defects Research 109:1568-1585, 2017. © 2017 Wiley Periodicals, Inc.

[In vivo screening of illegal drug].

The neuro-behavioral observation scorebook that improved the previous observation methods of Irwin was followed, the test material was administered to 5 mice per each group, and the mean value of the obtained score was determined. The behavior of a normal animal was assumed to be point 0, animals showing suppressive behavior were scored in the minus region, and animals that showed excitement behavior were scored in the plus region. Each score was divided into three stages, according to the level of strength of the biological effect. The score of each observation item was totaled, and the level of the strength of the biological effect in the item was judged according to its mean value. These test methods of neuro-behavioral observations we proposed were able to detect the biological effects of a drug simply and promptly, and contributed sufficient data to support an administrative measure aimed at anticipating and improving the prevention of health damage in humans by non-regulated drugs from a scientific perspective. Recently, we developed a method of serial measurement of the quantity of monoamine in the mouse central nervous system by microdialysis, and performed it. The Kanagawa Prefectural Institute of Public Health conducted a study of the biological effect of non-regulated drugs. A characteristic here is what they examined about drug-dependency other than observing the behavior of the animal.

Reproductive and neurobehavioural toxicity study of Ponceau 4R administered to mice in the diet.

Ponceau 4R was given to mice in the diet at levels of 0 (control), 0.12%, 0.24%, and 0.48% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(1) generation, and selected reproductive and neurobehavioural parameters were measured. There was no adverse effect of Ponceau 4R on litter size, litter weight or sex ratio at birth. The average body weight of male and female offspring was increased significantly in the high-dose group at postnatal days (PNDs) 0, 4 and 21. In behavioural developmental parameters, surface righting at PND 4 was affected significantly in the high-dose group in male offspring. Other variables measured showed no consistently significant adverse effect on either sex in the lactation period. In multiple water T-maze performance in the F(1) generation, the time taken was significantly longer than the control in the middle-dose and high-dose groups in males, and those effects were significantly dose-related (P<0.01). The dose level of Ponceau 4R in the present study produced no adverse effect on reproduction, and a few adverse effects on neurobehavioural parameters in mice. The non-observed adverse effect level (NOAEL) was presumed to be 0.12% in the diet (approximately 205mg/kg per day) for maze learning by males in the F(1) generation. Nevertheless, the middle-dose and high-dose levels were in excess of the acceptable daily intake (ADI) of Ponceau 4R (0-4.0mg/kg body weight), and the actual dietary intake of Ponceau 4R in humans is presumed to be much lower. It would appear, therefore, that the level of dietary intake of Ponceau 4R is unlikely to produce any adverse reproductive or neurobehavioural effect in humans.