Occupational Exposure Limits for Ethyl Benzene, Dimethyl Terephthalate and Hydrogen Fluoride, and Carcinogenicity and Reproductive Toxicant Classifications

Ethylbenzene [CAS No. 100-41-4] is a colorless liquid (boiling point 136.2℃, vapor pressure 1.27 kPa [25℃]) that is used as a raw material in the manufacture of stylene monomer, plastic, and rubber, and is a component of mixed xylene. This chemical was recommended at 100 ppm (430 mg/m3) for OEL-M in 1978, and revised at 50 ppm (217 mg/m3) and categorized Group 2B for class of carcinogenicity in 2001, and classified Group 2 as a reproductive toxicant in 2014. The JSOH reevaluated the occupational exposure limits (OEL) by examining subsequent reports this time, and proposed 20 ppm as OEL-M for ethylbenzene based on significant hearing loss in workers exposed to 30 ppm and noise in comparison with workers exposed to only nose,1 significant loss of outer hair cell of cochlear nerve at concentrations ≧200 ppm in 13 weeks inhalation study (0, 200, 400, 600, 800 ppm) in SD rats,2 and significant increase of auditory threshold ≧400 ppm in 5 days inhalation study (0, 300, 400, 550 ppm) in WAG/Rij rats.3 Skin absorption notation is indicated, and classifications of carcinogenic (Group 2B) and reproductive toxicant (Group 2) remain the same. Dimethyl terephthalate [CAS No. 120-61-6] is white flakes (melting point 140℃, boiling point 288℃), and used as a material in the manufacture of polybuthylene terephtharate, film, polyester fiber. The JSOH proposed 8 mg/m3 as OEL-M for dimethyl terephthalate based on the results of animal experiment.4 Nose rubbing, preening, and blinking were found at the concentration of 86.4 mg/m3, but not at that of 16.5 mg/m3 in male Long-Evans rats for 5 days 4-hour inhalation exposures per week for 58 days. Hydrogen fluoride [CAS No. 7664-39-3] is colorless corrosive gas and/or fume (melting point − 83℃, boiling point 20℃, vapor pressure 122 kPa [25℃]). It is used as a raw material of fluorine compounds, alkylating agent, and etching agent for glass and silica. The OEL-Ceiling, defined as the reference value to the maximal exposure concentration of the substance during a working day at or below which adverse health effects do not appear in most workers, of 3.0 ppm (2.5 mg/m3) is proposed based on the increased symptom scores from upper airways of human volunteer experiments.5, 6 Symptoms in upper airways in human volunteers exposed to 2.5-5.2 mg/m3 were significantly increased compared to those exposed to 0.2-0.6 and 0.7-2.4 mg/m3. In another human volunteer experiment, five volunteers suffered face flush at 5 days 6-hour exposures per week during 10-50 days. Skin absorption notation is indicated. N,N-dimethylformamide is proposed to be a Group 2A carcinogen. Proposed Group 2B carcinogens are ethylbenzene, 4-chlorobenzotrifluoride, and 1-bromo-3-chloropropane. Reproductive toxicants classification for ethylbenzene is proposed as Group 2. The latest OEL recommendations (2020-2021) will appear in the Environmental and Occupational Health Practice (Volume 2) as an open access. A brief summary of the proposal will be posted at the society's website (https://www.sanei.or.jp/oel-eng) in September. Approval of the research protocol: N/A. Informed consent: N/A. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. Conflict of interest: None declared. All the authors contributed draft preparation and deliberation of the proposals in the committee. The corresponding author (TN) developed and finalized the article based on the comments from all other authors’ feedback. Atsuko Araki1, Kenichi Azuma2, Ginji Endo3, Yoko Endo4, Tetsuhito Fukushima5, Kunio Hara6, Hajime Hori6, Masayoshi Ichiba7, Tatsuya Ishitake8, Gaku Ichihara9, Akiyoshi Ito6, Yuki Ito10, Satoko Iwasawa11, Takeyasu Kakamu5, Michihiro Kamijima10, Kanae Karita12, Takahiko Katoh13, Toshio Kawai14, Toshihiro Kawamoto3, Reiko Kishi1, Shinji Kumagai, Yukinori Kusaka15, Muneyuki Miyagawa16, Hiroyuki Miyauchi6, Yasuo Morimoto6, Kasuke Nagano17, Hisao Naito18, Tamie Nakajima19, Makiko Nakano20, Tetsuo Nomiyama21,‡, Hirokazu Okuda22, Masayuki Okuda23, Kazuyuki Omae20, Kazuhiro Sato15, Tomotaka Sobue24, Yasushi Suwazono25, Toru Takebayashi20, Tatsuya Takeshita26, Teruomi Tsukahara21, Masashi Tsunoda11, Jun Ueyama27, Yumi Umeda22, Kenya Yamamoto28, Yuko Yamano29, Takenori Yamauchi29 and Eiji Yano16 Authors listed alphabetically. 1Hokkaido University, 2Kindai University, 3Japan Industrial Safety and Health Association, 4Endo Occupational Health Consultant Office, 5Fukushima Medical University, 6University of Occupational and Environmental Health, Japan, 7Saga University, 8Tokyo University of Science, 9Kurume University, 10Nagoya City University, 11National Defense Medical College, 12Kyorin University, 13Kumamoto University, 14Kansai Technical Center for Occupational Medicine, 15University of Fukui, 16Teikyo University, 17Nagano Toxicologic-Pathology Consulting, 18Kinjo Gakuin University, 19Chubu University, 20Keio University, 21Shinshu University, 22Japan Bioassay Research Center, 23Yamaguchi University, 24Osaka University, 25Chiba University, 26Wakayama Medical University, 27Nagoya University, 28Showa University, and ‡ corresponding author