TR 095 Vol I – The Toxicology of Glycol Ethers and its Relevance to Man (Fourth Edition) Volume I

Abstract

TR 095 Vol I : The Toxicology of Glycol Ethers and its Relevance to Man (Fourth Edition) Volume I | March 2005

This report provides an update of an earlier ECETOC reviewa of a number of important ethylene and propylene glycol mono-ethers and di-ethers (glymes). It includes substantial new information concerning the human health consequences of exposure to this class of chemicals. The report presents toxicity data profiles for each individual compound.

Glycol mono-ethers are liquids that combine the solubility characteristics of ethers and alcohols since both functional groups are present. As a result, they are widely used in solvent applications, including formulations such as paints, inks and cleaning fluids. Non-solvent applications include uses as anti-icing agents in jet fuel, hydraulic system fluids and as chemical intermediates.

The hazard assessment of several glycol ethers can be based on short-term exposure studies because long-term exposure have not lead to more severe or different systemic effects. Glycol ethers have the potential to penetrate the skin (as a liquid or vapour) and this, therefore, represents a potentially significant route of exposure.

The majority of glycol ethers are of low acute toxicity; the main effect seen in laboratory animals at high doses is narcosis, typical of many solvents. Some glycol ethers are eye irritants. Overall, numerous studies with glycol ethers show that they do not exhibit genotoxic activity. The results of carcinogenicity studies with glycol ethers are consistent with this lack of genotoxic activity.

The systemic toxicity of the ethylene-based glycol ethers is mediated by their metabolism to the corresponding alkoxyacetic acids. Methyl- and ethyl-substituted ethylene glycol ethers can cause bone marrow depression, testicular atrophy, developmental toxicity, and immunotoxicity in animals. It should be noted that methyl- and ethyl-ethers of ethylene glycol are not used in consumer products in Europe. In contrast, the longer chain ethylene glycol ethers (ethylene glycol butyl ether, propyl ether, isopropyl ether and phenyl ether) do not cause any of these effects. Toxicity commonly associated with the longer chain homologues involves red blood cell haemolysis (anaemia), to which humans are resistant. The alkoxyacetic acid metabolites of glycol ethers are responsible for the haemolysis.

None of the ethylene-bond effects have been observed for the propylene glycol ethers (a isomers in commercial products); they are secondary alcohols and cannot be metabolised to their corresponding alkoxypropionic acids. Propylene glycol ethers are dealkylated to propylene glycol and then oxidised. The only change observed with propylene glycol ethers is an adaptive liver response and male rat kidney toxicity, which is not considered relevant to humans.

Reports of a number of effects in humans have been associated with glycol ether exposure, such as anaemia, granulocytopenia and leukopenia, increased risk of abortion or reduced sperm count in painters. Many such reports relate to methyl- and ethyl-substituted glycol ethers and are confounded by simultaneous exposures to other chemicals as well as limited information on exposure levels, which do not allow firm conclusions to be made concerning the contribution of glycol ethers to the observed effects. The toxicological findings reported to date indicate that, except for haemolytic anaemia and the liver and kidney effects in long-term studies, the effects seen in animals are also relevant to humans.

a ECETOC. 1995. The toxicology of glycol ethers and its relevance to man. Technical Report 64. European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium [ISSN-0773-8072-64]