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Gaku Ichihara,¹ Weihua Li,² Eiji Shibata,³ Xuncheng Ding,² Hailan Wang,¹ Yideng Liang,⁴ Simeng Peng,⁵ Seiichiro Itohara,¹ Michihiro Kamijima,¹ Qiyuan Fan,² Yunhui Zhang,² Enhong Zhong,² Xiaoyun Wu,² William M. Valentine,⁶ and Yasuhiro Takeuchi⁷

¹Field of Social Life Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; ²Shanghai Institute of Planned Parenthood Research, Shanghai, China; ³Department of Health and Psychosocial Medicine, Aichi Medical University, Aichi, Japan; ⁴Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; ⁵Yixing Anti-Epidemic and Health Station, Yixing, China; ⁶Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; ⁷Emeritus Professor, Nagoya University, Nagoya, Japan

Abstract
We reported recently that 1-bromopropane (1-BP ; n-propylbromide, CAS Registry no. 106-94-5) , an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP) , showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34-49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system. Key words: 1-bromopropane, distal latency, nerve conduction velocity, neurobehavioral testing, neurotoxicity, ozone-depleting solvents, postural sway testing, reproductive toxicity, vibration sense. Environ Health Perspect 112:1319-1325 (2004) . doi:10.1289/ehp.6995 available via http://dx.doi.org/ [Online 30 June 2004]

Address correspondence to G. Ichihara, Field of Social Life Science, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Telephone: 81-52-744-2123. Fax: 81-52-744-2126. E-mail: gak@med.nagoya-u.ac.jp

We thank Z.-Q. Chen, School of Medicine, Fudan University, and K. Yokoyama, Department of Public Health, School of Medicine, Mie University, for their help in conducting neurobehavioral tests. We also thank Y. Koike, Department of Medical Technology, Nagoya University School of Health Sciences, and T. Kondo, Nihon Kohden Co. Ltd., for their support in electrophysiologic examination.

This study was supported by grants 13470088 and 14406015 from the Japan Society for the Promotion of Science.

The authors declare they have no competing financial interests.

Received 2 February 2004 ; accepted 30 June 2004.

The formula for calculating the time-weighted average (TWA) was updated on 10 August, 2004.