Acute toxicity classification for ethylene glycol mono-n-butyl ether under the Globally Harmonized System

Acute oral, dermal and inhalation toxicity classifications of chemicals under the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) should typically be based on data from rats and rabbits, with the tacit assumption that such characterizations are valid for human risk. However this assumption is not appropriate in all cases. A case in point is the acute toxicity classification of ethylene glycol mono-n-butyl ether (EGBE, 2-butoxyethanol, CAS 111-76-2), where acute toxicity data from rats or rabbits leads to an overly conservative assessment of toxicity. Hemolysis is the primary response elicited in sensitive species following EGBE administration and the proximate toxicant in this response is 2-butoxyacetic acid (BAA), the major metabolite of EGBE. The sensitivity of erythrocytes to this effect varies between species; rats and rabbits are sensitive to BAA-mediated hemolysis, whereas humans and guinea pigs are not. In this publication, a weight of evidence approach for the acute hazard classification of EGBE under GHS is presented. The approach uses acute toxicity data from guinea pigs with supporting mechanistic and pharmacokinetic data in conjunction with human experience and shows that adopting the standard method results in over-classification.