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A toxicological review of the ethylene glycol series: Commonalities and differences in toxicity and modes of action.

Authors
  • Fowles, Jeff1
  • Banton, Marcy2
  • Klapacz, Joanna3
  • Shen, Hua4
  • 1 Tox-Logic Consulting, Santa Rosa, CA, USA. Electronic address: [email protected]
  • 2 Lyondell Chemical Company, Houston, TX, USA.
  • 3 Dow Chemical Company, Midland, MI, USA.
  • 4 Shell Oil Company, Houston, TX, USA.
Type
Published Article
Journal
Toxicology letters
Publication Date
Aug 15, 2017
Volume
278
Pages
66–83
Identifiers
DOI: 10.1016/j.toxlet.2017.06.009
PMID: 28689762
Source
Medline
Keywords
License
Unknown

Abstract

This review summarizes the hazards, exposure and risk that are associated with ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and penta-EG. All of the EGs are quickly and extensively absorbed following ingestion and inhalation, but not by the dermal route. Metabolism involves oxidation to the mono- and dicarboxylic acids. Elimination is primarily through the urine as the parent compound or the monoacid, and, in the case of EG, also as exhaled carbon dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS depression and metabolic acidosis in humans and rodents; the larger molecules being proportionally less acutely toxic on a strict mg/kg basis. Species differences exist in the metabolism and distribution of toxic metabolites, particularly with the formation of glycolic acids and oxalates (OX) from EG and diethylene glycol (DEG); OX are not formed to a significant degree in higher ethylene glycols. Among rodents, rats are more sensitive than mice, and males more sensitive than females to the acute and repeated-dose toxicity of EG. The metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are associated with nephrotoxicity in humans and rodents following single and repeated exposures. However, physiological and metabolic differences in the rate of formation of GA, DGA and OX and their distribution result in EG and DEG causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity indicates that EG and its higher oligomers are not anticipated to be embryotoxic in humans at environmentally relevant doses. None of the compounds present developmental toxicity concerns at doses that do not also cause significant maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented, which considers the common and distinct toxicological properties of each compound. It is concluded that EGs pose no risk to human health as a result of their intended use patterns.

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