Concentration-time extrapolation of short-term inhalation exposure levels: dimethyl sulfide, a case study using a chemical-specific toxic load exponent.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8910739 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-7691 (Electronic) Linking ISSN: 08958378 NLM ISO Abbreviation: Inhal Toxicol

Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : Hemisphere Pub. Corp., c1989-

Air Pollutants*/standards ; Air Pollutants*/toxicity ; Inhalation Exposure*/adverse effects ; Inhalation Exposure*/standards ; Irritants*/standards ; Irritants*/toxicity ; Sulfides*/standards ; Sulfides*/toxicity ; Threshold Limit Values*; Administration, Inhalation ; Animals ; Coma/chemically induced ; Humans ; Odorants ; Risk Assessment ; Time Factors

Objective: Dimethyl sulfide (DMS, CAS 75-18-3) is an industrial chemical. It is both an irritant and neurotoxicant that may be life-threatening because of accidental release. The effects of DMS on public health and associated public health response depend on the exposure concentration and duration. However, currently, public health advisory information exists for only a 1 h exposure duration, developed by the American Industrial Hygiene Association (AIHA). In the present work, the AIHA-reviewed data were computationally extrapolated to other common short-term durations.
Methods: The extrapolation was carried out using the toxic load equation, C ⁿ  × t = TL, where C and t are exposure concentration and duration, TL is toxic load, and n is a chemical-specific toxic load exponent derived in the present work using probit meta-analysis. The developed threshold levels were vetted against the AIHA database of clinical and animal health effects induced by DMS.
Results: Tier-1 levels were derived based on human exposures that resulted in an easily detectable odor, because DMS is known to have a disagreeable odor that may cause nausea. Tier-2 levels were derived from the lower 95% confidence bounds on a benchmark concentration that caused 10% incidence (BMCL 10 ) of coma in rats during a 15 min inhalation exposure to DMS. Tier-3 levels were based on a BMCL 05 for mortality in rats.
Conclusion: Emergency responders and health assessors may consider these computationally derived threshold levels as a supplement to traditional chemical risk assessment procedures in instances where AIHA developed public health advisory levels do not exist.

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CC999999 United States ImCDC Intramural CDC HHS

Keywords: AEGL; ERPG; TLE; dimethyl sulfide; health guidance value; inhalation; inhalation exposure; n-value; toxic load; volatile organic compound

0 (Air Pollutants)
0 (Irritants)
0 (Sulfides)
QS3J7O7L3U (dimethyl sulfide)

Date Created: 20190103 Date Completed: 20190820 Latest Revision: 20240402

20240402

PMC8260034

10.1080/08958378.2018.1551444

30600740