A cross-sectional observation of the health effects of hydrazine hydrate and differences of its metabolism by NAT2 polymorphism

Objectives: To summarize the results of two studies that attempted to clarify: (1) the health effects of hydrazine hydrate (HH) (N₂H₄·H₂O: CAS No. 7803-57-8); and (2) the influence of allelic polymorphism of N-acetyltransferase (NAT2) on the metabolism of HH. Methods: A cross-sectional survey was carried out on 172 male HH-exposed workers and 125 male referent workers at five factories in Japan. The biological half-lives of HH after 1 h of exposure were determined in 12 workers, four workers in each of three NAT2 phenotypes. Clinical examinations were performed and acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. NAT2 phenotypes were assessed. Results: No hydrazine was detected in either the breathing zones or the urine of the referent workers. The mean hydrazine concentration in the breathing zones, hydrazine and acetylhydrazine in urine, and the cumulative exposure level were 0.0109 ppm, 0.8660 μmol/g·Cr, and 2.80 ppm-years, respectively. There was no difference and no dose-dependent change in the health examination items between HH-exposed and referent workers after adjusting confounding factors, nor in terms of the differences of NAT2 phenotypes. Of 90 subjective symptoms, complaints of nightmares were significantly related to HH exposure. The half-life of urinary hydrazine and acetylhydrazine on rapid, intermediate, and slow phenotypes was 1.68, 3.01, and 4.46 h, respectively. Conclusion: This study suggested that current and cumulative exposure to HH did not affect the workers' health, and the half-life of the slow phenotype was longer than those of the rapid and intermediate phenotypes.