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.

journal_name

Inhal Toxicol

journal_title

Inhalation toxicology

authors

Demchuk E,Ball SL,Le SL,Prussia AJ

doi

10.1080/08958378.2018.1551444

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

448-462

issue

11-12

eissn

0895-8378

issn

1091-7691

journal_volume

30

pub_type

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