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.
Boatman Toxicology Consulting LLC, 8 Osage Trail, Spencerport, NY 14559, USA. Electronic address: rboatman@rochester.rr.com.
Rodney
R
Boatman
Chemsage Limited, PO Box 431, Fleet, Hampshire GU51 9BP, United Kingdom. Electronic address: jeff@chemsage.co.uk.
Jeffrey
J
Kelsey
Toxicology & Environmental Research and Consulting (TERC), Environment, Health and Safety (EH&S), Dow Europe GmbH, Bachtobelstrasse 3, CH-8810 Horgen, Switzerland. Electronic address: NBall@dow.com.
Nicholas
N
Ball
D000818:Animals; D004285:Dogs; D005026:Ethylene Glycols / Q000145:classification* / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D015386:Hazardous Substances / Q000145:classification / Q000633:toxicity; D006461:Hemolysis; D006801:Humans; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute
D005026:Ethylene Glycols; D015386:Hazardous Substances; C017096:n-butoxyethanol
2-Butoxyethanol; Acute toxicity; CAS No. 111-76-2; Ethylene glycol mono-n-butyl ether; GHS classification; Guinea pig; Hemolysis; Species difference