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

Abstract

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, Cⁿ × 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 (BMCL₁₀) of coma in rats during a 15 min inhalation exposure to DMS. Tier-3 levels were based on a BMCL₀₅ 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.

Keywords:

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

Acknowledgements

The authors thank Rich Nickle and Jim Holler for stimulating discussions and sharing expertise, Kim Gehle for careful proofreading and helpful comments. S.L.B. and S.L.L. were supported, respectively, by a fellowship from the Oak Ridge Institute for Science and Education and the Rollins Earn and Learn program from the Emory University.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Agency for Toxic Substances and Disease Registry.

Disclosure statement

No potential conflict of interest was reported by the authors.