A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers' Health

Tetsuo NOMIYAMA; Kazuyuki OMAE; Shigeru TANAKA; Hiroyuki MIYAUCHI; Akio KOIZUMI; Mikako TSUKADA; Yasuhiko WADA; Takashi MOGI; Shunichiro IMAMIYA; Haruhiko SAKURAI

doi:10.1539/joh.40.177

Tetsuo NOMIYAMA, Kazuyuki OMAE, Shigeru TANAKA, Hiroyuki MIYAUCHI, Akio KOIZUMI, Mikako TSUKADA, Yasuhiko WADA, Takashi MOGI, Shunichiro IMAMIYA, Haruhiko SAKURAI

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Keywords: Hydrazine hydrate, NAT2, Polymorphism, Cross-sectional study, Phenotype

JOURNAL FREE ACCESS

1998 Volume 40 Issue 3 Pages 177-185

DOI https://doi.org/10.1539/joh.40.177

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Published: 1998 Received: July 18, 1997 Available on J-STAGE: April 07, 2006 Accepted: June 12, 1998 Advance online publication: - Revised: -
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Date of correction: April 07, 2006 Reason for correction: - Correction: TITLE Details: Wrong : A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers'' Health
Right : A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers' Health

Date of correction: April 07, 2006 Reason for correction: - Correction: ABSTRACT Details: Wrong : A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers'' Health: Tetsuo NOMIYAMA, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University-Objective: To clarify the current and cumulative effects of hydrazine hydrate (HH) (N₂H₄ • H₂O: CAS No. 7803-57-8) on workers'' health. Methods: A cross-sectional survey was carried out on 172 male HH-exposed workers (age 18-60, mean 39.6; exposure duration 0.50-34.17) and 125 male referent workers (age 19-58, mean 40.9) at 5 factories making HH or hydrazine derivatives in Japan. Current exposure concentrations were assessed by determining hydrazine in the breathing zones and urinary hydrazine + acetylhydrazine. The cumulative exposure level was assessed by multiplying the individuais'' working durations at the job sites and the estimated past environmental levels at the job sites. Clinical examinations were performed with particular focus on hepatic and renal function tests. N-acetyltransferase (NAT2) phenotypes were assessed. Acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. 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 + acetylhydrazine in urine, and cumulative exposure level were 0.0109 ppm (N.D.-0.2003), 0.8660μmol/g • Cr (N.D.-14.20), and 2.80 ppm-years (0.003-19) respectively. There was no difference and no dosedependent change in either the means or the prevalence of abnormal findings in health examination items between the HH-exposed and the referent workers after adjusting confounding factors and by means of the differences of NAT2 phenotypes. Among 90 subjective symptoms, complaint of “nightmares” was significantly related to HH exposure. Conclusion: In this study, no health effect regarding current and cumulative HH exposure was observed in the HH-exposed workers when compared to the referent workers.
Right : A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers' Health: Tetsuo NOMIYAMA, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University-Objective: To clarify the current and cumulative effects of hydrazine hydrate (HH) (N₂H₄ • H₂O: CAS No. 7803-57-8) on workers' health. Methods: A cross-sectional survey was carried out on 172 male HH-exposed workers (age 18-60, mean 39.6; exposure duration 0.50-34.17) and 125 male referent workers (age 19-58, mean 40.9) at 5 factories making HH or hydrazine derivatives in Japan. Current exposure concentrations were assessed by determining hydrazine in the breathing zones and urinary hydrazine + acetylhydrazine. The cumulative exposure level was assessed by multiplying the individuais' working durations at the job sites and the estimated past environmental levels at the job sites. Clinical examinations were performed with particular focus on hepatic and renal function tests. N-acetyltransferase (NAT2) phenotypes were assessed. Acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. 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 + acetylhydrazine in urine, and cumulative exposure level were 0.0109 ppm (N.D.-0.2003), 0.8660μmol/g • Cr (N.D.-14.20), and 2.80 ppm-years (0.003-19) respectively. There was no difference and no dosedependent change in either the means or the prevalence of abnormal findings in health examination items between the HH-exposed and the referent workers after adjusting confounding factors and by means of the differences of NAT2 phenotypes. Among 90 subjective symptoms, complaint of “nightmares” was significantly related to HH exposure. Conclusion: In this study, no health effect regarding current and cumulative HH exposure was observed in the HH-exposed workers when compared to the referent workers.

Date of correction: April 07, 2006 Reason for correction: - Correction: CITATION Details: Wrong : 1) Ekshtat BY. Maximum permissible concentrations of HH and phenylhydrazine in water bodies. Hyg Sanit 1965; 30: 191-197.
2) Bozo Research Center Inc. An acute dermal toxicity study of 100% HH (N₂H₄ • H₂O) in rabbits. Bozo Research Center Inc. B-2485 1993.
3) Huntingdon Research Centre. Hydrazine 64% aqueous solution. Acute inhalation toxicity in rats 1-hour exposure. HRC Report 1993.
4) Reid FJ. Hydrazine and lupus. Br Med J 1965; 2: 1246.
5) Evans DM. Two cases of HH dermatitis without systemic intoxication. Br J Ind Med 1959; 16: 126-127.
6) Sotaneimi E, Hirvonen J, Isomaki H, Takkunen J, Kaila J. Hydrazine toxicity in the human report of fetal case. Ann Clin Res 1971; 3: 30-33.
7) Richter ED, Gal A, Bitchatchi E, et al. Residual neurobehavioral impairment in a water technician exposed to hydrazine-containing mixture. Israel J Med Sci 1992; 28: 598-602.
8) Wald N, Boreham J, Doll R, Bonsall J. Occupational exposure to hydrazine and subsequent risk of cancer. Br J Ind Med 1984; 41: 31-34.
9) Morris J, Densem JW, Wald NJ, Doll R. Occupational exposure to hydrazine and subsequent risk of cancer. Occup Environ Med 1995; 52: 43-45.
10) Haun CC, Kinkead ER. Chronic inhalation toxicity of hydrazine. In: Proceeding of the 4th Annual Conference on Environmental Toxicology, Aerospace Medical Research Laboratory, Wright Patterson Air Force Base, OH. 1973: 351-363.
11) MacEwen JD, McConnell EE, Beck KC. The effects of 6-month chronic low level inhalation exposures to hydrazine on animals. In: Proceeding of the 5th Annual Conference on Environmental Toxicology, Aerospace Medical Research Laboratory, Wright Patterson Air Force Base, OH. 1974: 225-235.
12) Vernot EH, MacEwen JD, Bruner RH, et al. Long term inhalation toxicity of hydrazine. Fund Appl Toxicol 1985; 5: 1050-1064.
13) International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol. 4, Some Aromatic Amines, Hydrazine and Related Substances, N-Nitroso Compounds and Miscellaneous Alkylating Agents. Lyon: IARC, 1974: 127-136.
14) ACGIH. 1996-1997. Threshold limit values for chemical substances and physical agents and Biological Exposure Indices. Cincinnati: ACGIH, 1996.
15) NIOSH. Manual of Analytical Methods, 3rd edition, P & CAM 248 Hydrazine Compounds. In: Air. U.S. Department of Health, Education, and Welfare 1977; 1: 248-1-248-6.
16) Trmbrell JA, Harland SJ. Identification and quantification of hydrazine in the urine of patients treated with hydralazine. Clin Pharmacol Ther 1979; 26: 81-88.
17) Lin HJ, Han C, Lin BK, Hardy S. Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians. Blacks. Hispanics, and Whites: Application to metabolic epidemiology. Am J Hum Genet 1993; 52: 827-834.
18) Inoue T. A table for subjective symptom questionnaires for solvent workers. In: Japan Industrial Health and Safety Association, ed. Health management of solvent workers. Tokyo: Japan Industrial Health and Safety Association, 1993; 66-67 (in Japanese).
19) Japan Society of Occupational Health. Reconunendation of occupational exposure limits (1994). Jpn J Ind Health 1994; 36: 273-276.
20) Tanaka T, Nagai M, Yoshihara S,et al. Changing pattem of age-specific prevalence of hepatitis B surface antigen and corresponding antibody in Japan. Am J Epidemiol 1986; 124: 368-371.
21) Nishioka K. Hepatitis C virus infection in Japan. Gastroenterol Jpn 1991; 26 suppl 3: 152-155.
22) Akbar SM, Onji M. Kanaoka M, et al. The seroepidemiology of hepatitis A and B in a Japanese town. Asia-Pacific J Public Health 1992-93; 6: 26-29.
23) Lindelof B, Alnkvist O, Gothe CJ. Sleep disturbances and exposure to organic solvents. Arch Environ Health 1992; 47: 104-106.
24) Kishi R, Itoh I, Shizu S, Harabuchi I, Miyake H. Symptoms among workers with long-term exposure to methyl bromide. An epidemiological study. Jpn J Ind Health 1991; 33: 241-250.
25) Koizumi A, Nomiyama T, Tsukada M, et al. Evidence of N-acetyltransferase allele associated metabolisms of hydrazine in Japanese workers. J Occup Environ Med 1998; 40: 217-222.

Right : 1) Ekshtat BY. Maximum permissible concentrations of HH and phenylhydrazine in water bodies. Hyg Sanit 1965; 30: 191-197.
2) Bozo Research Center Inc. An acute dermal toxicity study of 100% HH (N₂H₄ • H₂O) in rabbits. Bozo Research Center Inc. B-2485 1993.
3) Huntingdon Research Centre. Hydrazine 64% aqueous solution. Acute inhalation toxicity in rats 1-hour exposure. HRC Report 1993.
4) Reid FJ. Hydrazine and lupus. Br Med J 1965; 2: 1246.
5) Evans DM. Two cases of HH dermatitis without systemic intoxication. Br J Ind Med 1959; 16: 126-127.
6) Sotaneimi E, Hirvonen J, Isomaki H, Takkunen J, Kaila J. Hydrazine toxicity in the human report of fetal case. Ann Clin Res 1971; 3: 30-33.
7) Richter ED, Gal A, Bitchatchi E, et al. Residual neurobehavioral impairment in a water technician exposed to hydrazine-containing mixture. Israel J Med Sci 1992; 28: 598-602.
8) Wald N, Boreham J, Doll R, Bonsall J. Occupational exposure to hydrazine and subsequent risk of cancer. Br J Ind Med 1984; 41: 31-34.
9) Morris J, Densem JW, Wald NJ, Doll R. Occupational exposure to hydrazine and subsequent risk of cancer. Occup Environ Med 1995; 52: 43-45.
10) Haun CC, Kinkead ER. Chronic inhalation toxicity of hydrazine. In: Proceeding of the 4th Annual Conference on Environmental Toxicology, Aerospace Medical Research Laboratory, Wright Patterson Air Force Base, OH. 1973: 351-363.
11) MacEwen JD, McConnell EE, Beck KC. The effects of 6-month chronic low level inhalation exposures to hydrazine on animals. In: Proceeding of the 5th Annual Conference on Environmental Toxicology, Aerospace Medical Research Laboratory, Wright Patterson Air Force Base, OH. 1974: 225-235.
12) Vernot EH, MacEwen JD, Bruner RH, et al. Long term inhalation toxicity of hydrazine. Fund Appl Toxicol 1985; 5: 1050-1064.
13) International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol. 4, Some Aromatic Amines, Hydrazine and Related Substances, N-Nitroso Compounds and Miscellaneous Alkylating Agents. Lyon: IARC, 1974: 127-136.
14) ACGIH. 1996-1997. Threshold limit values for chemical substances and physical agents and Biological Exposure Indices. Cincinnati: ACGIH, 1996.
15) NIOSH. Manual of Analytical Methods, 3rd edition, P & CAM 248 Hydrazine Compounds. In: Air. U.S. Department of Health, Education, and Welfare 1977; 1: 248-1-248-6.
16) Trmbrell JA, Harland SJ. Identification and quantification of hydrazine in the urine of patients treated with hydralazine. Clin Pharmacol Ther 1979; 26: 81-88.
17) Lin HJ, Han C, Lin BK, Hardy S. Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians. Blacks. Hispanics, and Whites: Application to metabolic epidemiology. Am J Hum Genet 1993; 52: 827-834.
18) Inoue T. A table for subjective symptom questionnaires for solvent workers. In: Japan Industrial Health and Safety Association, ed. Health management of solvent workers. Tokyo: Japan Industrial Health and Safety Association, 1993; 66-67 (in Japanese).
19) Japan Society of Occupational Health. Reconunendation of occupational exposure limits (1994). Jpn J Ind Health 1994; 36: 273-276.
20) Tanaka T, Nagai M, Yoshihara S,et al. Changing pattem of age-specific prevalence of hepatitis B surface antigen and corresponding antibody in Japan. Am J Epidemiol 1986; 124: 368-371.
21) Nishioka K. Hepatitis C virus infection in Japan. Gastroenterol Jpn 1991; 26 suppl 3: 152-155.
22) Akbar SM, Onji M. Kanaoka M, et al. The seroepidemiology of hepatitis A and B in a Japanese town. Asia-Pacific J Public Health 1992-93; 6: 26-29.
23) Lindelof B, Alnkvist O, Gothe CJ. Sleep disturbances and exposure to organic solvents. Arch Environ Health 1992; 47: 104-106.
24) Kishi R, Itoh I, Shizu S, Harabuchi I, Miyake H. Symptoms among workers with long-term exposure to methyl bromide. An epidemiological study. Jpn J Ind Health 1991; 33: 241-250.
25) Koizumi A, Nomiyama T, Tsukada M, et al. Evidence of N-acetyltransferase allele associated metabolisms of hydrazine in Japanese workers. J Occup Environ Med 1998; 40: 217-222.

Date of correction: April 07, 2006 Reason for correction: - Correction: PDF FILE Details: -

Abstract

A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers' Health: Tetsuo NOMIYAMA, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University-Objective: To clarify the current and cumulative effects of hydrazine hydrate (HH) (N₂H₄ • H₂O: CAS No. 7803-57-8) on workers' health. Methods: A cross-sectional survey was carried out on 172 male HH-exposed workers (age 18-60, mean 39.6; exposure duration 0.50-34.17) and 125 male referent workers (age 19-58, mean 40.9) at 5 factories making HH or hydrazine derivatives in Japan. Current exposure concentrations were assessed by determining hydrazine in the breathing zones and urinary hydrazine + acetylhydrazine. The cumulative exposure level was assessed by multiplying the individuais' working durations at the job sites and the estimated past environmental levels at the job sites. Clinical examinations were performed with particular focus on hepatic and renal function tests. N-acetyltransferase (NAT2) phenotypes were assessed. Acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. 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 + acetylhydrazine in urine, and cumulative exposure level were 0.0109 ppm (N.D.-0.2003), 0.8660μmol/g • Cr (N.D.-14.20), and 2.80 ppm-years (0.003-19) respectively. There was no difference and no dosedependent change in either the means or the prevalence of abnormal findings in health examination items between the HH-exposed and the referent workers after adjusting confounding factors and by means of the differences of NAT2 phenotypes. Among 90 subjective symptoms, complaint of “nightmares” was significantly related to HH exposure. Conclusion: In this study, no health effect regarding current and cumulative HH exposure was observed in the HH-exposed workers when compared to the referent workers.

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