Heihachiro Arito

Genotoxicity and cytotoxicity of multi-wall carbon nanotubes in cultured Chinese hamster lung cells in comparison with chrysotile A fibers.

Genotoxicity and Cytotoxicity of Multi‐wall Carbon Nanotubes in Cultured Chinese Hamster Lung Cells in Comparison with Chrysotile A Fibers: Masumi Asakura, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association

Brief naps during post-lunch rest: effects on alertness, performance, and autonomic balance.

Abstract This study was designed to examine the effects of brief naps taken after lunch on alertness, performance, and autonomic balance. Three groups each comprising ten healthy subjects, who had slept normally at home the previous night, were randomly assigned to groups taking one of three lengths of nap (0, 15, and 45 min) after lunch. The P300, an event-related potential which is a neurophysiological correlate of cognitive function, subjective sleepiness (visual analogue scale), and electrocardiogram were measured before, 30 min after, and 3 h after the naps. Each measurement was followed by an English transcription task lasting 90 min. The P300 latency was significantly shorter after the 15-min than after the 45-min nap, or after no nap had been taken, while its amplitude was not affected by the length of nap. Subjective sleepiness was lower after both naps than after no nap. The task performance was significantly better during the second half of the last task session after the 15-min nap than after no nap. The high-frequency component of the R-R interval spectrum increased significantly during the 45-min nap, showing a temporary shift to a predominance of the parasympathetic nervous system. Mean total sleep times during the 15- and 45-min naps were 7.3 and 30.1 min, respectively. These results would indicate that the 15-min nap may serve to shorten the stimulus evaluation time, reducing subjective sleepiness, and slightly improving task performance. Our data demonstrated that in our subjects a brief nap after lunch was effective for enhancing subsequent alertness and performance after normal sleep the previous night.

Inhalation Carcinogenicity and Chronic Toxicity of Indium-tin Oxide in Rats and Mice

Inhalation Carcinogenicity and Chronic Toxicity of Indium‐tin Oxide in Rats and Mice: Kasuke Nagano, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association—

Nurses' workload associated with 16-h night shifts. II: Effects of a nap taken during the shifts.

This study aimed at examining the effects on the subjective symptoms in nurses of both timing and length of a 2‐h nap during a 16‐h night shift. Compared to pre‐nap levels, sleepiness, fatigue, and dullness increased immediately after napping. Afterwards, sleepiness decreased significantly, and the other symptoms returned to the pre‐nap values. The nurses’ subjective symptoms after napping were not associated with the timing of the nap and post‐nap fatigue lasted longer as the nap time increased (> 1.5 h). These results suggest that for effective napping during long night shifts, the nap length should be determined carefully to avoid persistent sleep inertia.

Acute effects of toluene on circadian rhythms of sleep-wakefulness and brain monoamine metabolism in rats

Acute effects of a single i.p. injection of toluene on circadian rhythms of sleep-wakefulness were investigated in rats which were chronically implanted with EEG and EMG electrodes for polygraphic recordings. The toluene injection produced an initial increase in wakefulness (W) and a subsequent increase in slow-wave sleep (SWS) during the dark period. In an attempt to clarify mechanisms of these biphasic effects of toluene on sleep-wakefulness rhythms, brain monoamines and their metabolites were determined at the times of the initial increase in W and the increased SWS. The initial increase in W was associated with an increase in cortical NA, MHPG and 5-HT together with a decrease in cortical 5-hydroxyindoleacetic acid (5-HIAA), while the increased SWS during the dark period was associated with an increase in 5-HIAA and a concomitant decrease in 3-methoxy-4-hydroxyphenylglycol (MHPG). The toluene-induced changes in sleep-wakefulness seemed to be manifested at lower blood levels of toluene than the behavioral signs of central nervous system (CNS) depression. These biphasic effects of toluene on circadian sleep-wakefulness rhythms are discussed in terms of the reciprocal interactions between central 5-HT and NA neurons.

Carcinogenicity and chronic toxicity after inhalation exposure of rats and mice to N,N-dimethylformamide.

Carcinogenicity and Chronic Toxicity after Inhalation Exposure of Rats and Mice to N,N‐Dimethylformamide: Hideki Senoh, et al. Japan Bioassay Research Center—Carcinogenicity and chronic toxicity of N,N‐Dimethylformamide (DMF) were examined by inhalation exposure of groups of 50 rats and 50 mice of both sexes to DMF vapor at a concentration of 0, 200, 400 or 800 ppm (v/v) for 6 h/d, 5 d/wk, for 104 wk. In rats, incidences of hepatocellular adenomas and carcinomas significantly increased in the 400 and 800 ppm‐exposed groups and in the 800 ppm‐exposed group, respectively. The hepatocellular adenoma did not increase significantly in the 400 ppm exposed female rats, but its incidence exceeded a range of historical control data in the Japan Bioassay Research Center (JBRC). In mice, incidences of hepatocellular adenomas and carcinomas significantly increased in all the DMF‐exposed groups. Incidence of hepatoblastomas significantly increased in the 200 and 400 ppm‐exposed male mice, and 4 cases of hepatoblastomas in the 400 ppm‐exposed female mice and the 800 ppm‐exposed male mice exceeded the range of historical control data of the JBRC. Incidences of altered cell foci increased in the liver of exposed rats and mice in an exposure concentration‐related manner, and those foci were causally related to the hepatocellular tumors. Liver weights increased in both rats and mice exposed to DMF at 200 ppm and above. Increased levels of γ‐GTP, ALT, AST and total bilirubin in exposed rats of both sexes and AST and ALT in exposed mice of both sexes were noted. It was concluded that 2‐yr inhalation exposure to DMF increased incidences of hepatocellular adenomas and carcinomas in rats and incidences of hepatocellular adenomas, carcinomas and hepatoblastomas in mice, and that hepatocarcinogenicity of DMF was more potent in mice than in rats.

Two- and 13-week inhalation toxicities of indium-tin oxide and indium oxide in rats.

Two‐ and 13‐week Inhalation Toxicities of Indium‐tin Oxide and Indium Oxide in Rats: Kasuke Nagano, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association—

Carcinogenicity studies of 1,4-dioxane administered in drinking-water to rats and mice for 2 years

The carcinogenicity of 1,4-dioxane was examined by giving groups of 50 F344/DuCrj rats and 50 Crj:BDF(1) mice of each sex 1,4-dioxane in the drinking-water for 2 years. The concentrations of 1,4-dioxane were 0 (control), 200, 1000 and 5000 ppm (wt./wt.) for rats and 0, 500, 2000 and 8000 ppm for mice. The highest dose levels did not exceed the maximum tolerated dose. In the rat, there was significant induction of nasal squamous cell carcinomas in females and hepatocellular adenomas and carcinomas in males and females, peritoneal mesotheliomas in males, and mammary gland adenomas in females. In the mouse, there was significant induction of hepatocellular tumors in males and females. Two nasal tumors occurring in the 8000 ppm-dosed groups were spontaneously rare and, thus, were attributed to 1,4-dioxane exposure. The present studies provided clear evidence of carcinogenicity in rats and mice. Lifetime cancer risk of humans exposed to 1,4-dioxane through drinking-water was quantitatively estimated with a non-threshold approach by application of a linearized multistage model to dose-carcinogenic response relationships, in addition to a threshold approach for estimation of the tolerable daily intake using no-observed- or lowest-observed-adverse-effect levels of the carcinogenic responses and uncertainty factors.

Partial insomnia, hyperactivity and hyperdipsia induced by repeated administration of toluene in rats: Their relation to brain monoamine metabolism

In an attempt to examine chronic effects of toluene on sleep, spontaneous locomotor activity and drinking behavior, rats were repeatedly administered toluene i.p. at doses of 100 and 200 mg/kg body weight for 14 consecutive days. The 200-mg/kg injections induced a decrease in total sleep on Day 1, an increase in locomotor activity on Days 1 through 4 and an increase in drinking activity on Days 0 through 6 after discontinuation of the daily injections. Both the reduced sleep and the increased locomotor activity appeared during the light period, whereas the drinking activity increased during the dark period. In order to find neurochemical correlates of the toluene-induced changes in behavior, regional concentrations of brain monoamines and their metabolites were determined. The toluene-induced partial insomnia and hyperactivity were associated with lowered concentrations of serotonin in frontal cortex, hippocampus and midbrain and 5-hydroxyindoleacetic acid in midbrain and hypothalamus. The increased drinking activity was associated with increased concentrations of striatal 3,4-dihydroxy-phenylacetic acid and homovanillic acid and hypothalamic noradrenaline and 3-methoxy-4-hydroxyphenylethyleneglycol. Central monoaminergic mechanisms were implicated in the toluene-induced partial insomnia, hyperactivity and hyperdipsia.

Two-year inhalation study of carcinogenicity and chronic toxicity of 1,4-dioxane in male rats

Carcinogenicity and chronic toxicity of 1,4-dioxane were examined by inhalation exposure of 50 male F344 rats to 1,4-dioxane vapor at 0 (clean air), 50, 250, or 1250 ppm (v/v) for 6 h/day, 5 days/wk, and 104 wk. Survival rates of 250 and 1250 ppm-exposed groups were decreased near the end of the 2-yr exposure period, due probably to the occurrence of malignant tumors. A statistically significant but marginal decrement of terminal body weight (<10%) was found in the 1250 ppm-exposed group, suggesting slight systemic toxicity. Significant changes in plasma levels of AST, ALT, ALP, and γ-GTP and relative weight of the liver occurred in the 1250 ppm-exposed group. Dose-dependent and statistically significant increases in incidences of nasal squamous cell carcinomas, hepatocellular adenomas, and peritoneal mesotheliomas were found primarily in the 1250 ppm-exposed group. The incidences of renal cell carcinomas, fibroadenomas in the mammary gland, and adenomas in the Zymbal gland were also increased dose-dependently. Preneoplastic lesions occurred in the nasal cavity and liver of the 1,4-dioxane-exposed groups. As nonneoplastic lesions, the significantly increased incidences of nuclear enlargement, atrophy, and respiratory metaplasia in the nasal cavity were noted at 50 ppm and above. A LOAEL (lowest observed adverse effect level) was determined at 50 ppm for the nasal endpoint of general chronic toxicity. This study provides clear evidence of carcinogenicity for 1,4-dioxane in male rats. A cytotoxic-proliferative and in vivo genotoxic mode of action is suggested to operate in 1,4-dioxane-induced carcinogenesis.