Elsevier

Toxicology Letters

Volume 156, Issue 1, 28 March 2005, Pages 29-37
Toxicology Letters

The INSERM expert review on glycol ethers: findings and recommendations

https://doi.org/10.1016/j.toxlet.2003.12.077Get rights and content

Abstract

The use of glycol ethers and their effects on health have recently attracted the attention of the French health authorities. At their request, INSERM, the French Institute of Health and Medical Research, conducted a collective expertise review on glycol ethers in 1999. INSERM Expertise Reviews are independent procedures performed by experts from several disciplines, to guarantee the objectivity and the relevance of the report.

During several work sessions, the experts carried out a critical analysis of and reviewed studies concerning the toxicity of glycol ethers. This process resulted in a series of recommendations and conclusions. All these data have been published in the form of a report and have been used to help the public authorities to make decisions on how to prevent risks for professionals and consumers.

Introduction

The French National Institute for Health and Medical Research (INSERM) is a public scientific and technological institute with four main commitments: (1) to conduct research in the fields of biology, medicine and public health; (2) to train scientists, to provide information and to disseminate knowledge; (3) to transfer research outputs; (4) to develop national and international partnerships. One goal is to transfer and to share INSERM's research outputs through the development of expert reviews. Such reviews, also called collective expertise reviews, involve the critical analysis and synopsis of knowledge concerning medical or health issues and are performed at the request of health and government authorities or at the request of industrial and social partners. Once the questions to be answered have been defined, a group of scientific experts covering all required disciplines is brought together to address the question. This involves compiling a very detailed bibliography on the subject. The experts can also ask external experts for help with specific points. The scientific aspect is co-ordinated by INSERM's Collective Expertise Service, which decides, together with the party who requested the review, which questions need to be answered. The experts are chosen by INSERM on the basis of their areas of expertise and the absence of conflicts of interest. Several meetings are then organised so that the experts can provide their analysis based on available international data. A final report is then drawn up. This report can be divided into three parts: (1) data analysis; (2) summary; (3) conclusions and recommendations.

The INSERM expert review on glycol ethers was carried out in 1999 at the request of the Ministry of Environment and the Ministry of Employment and Solidarity. A final report was published at the end of 1999 (INSERM, 1999).

Section snippets

General characteristics and usage

An important property of glycol ethers is that they are soluble in water as well as in many organic solvents. Given their amphiphilic nature, they are used in numerous products for industrial and domestic usage. They act as stabilisers and have excellent technical properties. They are moderately volatile, colourless liquids that do not leave a residual smell. The chemical industry currently synthesises more than 30 different glycol ethers.

The synthesis of glycol ethers is based on the reaction

Professions exposed

Between 1983 and 1998, the INRS (the French National Research and Safety Institute) collected data concerning over 40,000 products (Sepia database). Nearly 10% of these products contained ethylene glycol ether derivatives and nearly 4% contained propylene glycol ether derivatives. The percentage of glycol ethers in these preparations is variable (from 0.1% to 100%). However, pure glycol ethers are only used in certain cases (e.g. EGEEA was used as a cleaning solvent by silk screen printers).

Effect on the environment

The production and use of glycol ethers can lead to their release into the environment. Recent data suggest that this takes place mainly in the aquatic environment. The half-life of EGBE has been estimated to be between 1 and 4 weeks in surface water and less than 2 months in underground water supplies. Given the predominance of glycol ethers in the aquatic environment, they have been tested on aquatic species and do not appear to have any short-term toxic effects. Although glycol ethers are

Effects on health

Animal studies have been carried out to determine the effects of short-term (acute effects) and medium-term (repeat exposure) exposure to glycol ethers (Table 3, Table 4). Most studies published in the international literature concern ethylene glycol ether derivatives in particular EGME, EGEE and their acetates. Nothing has been published on more than half of all glycol ethers. Some quantitatively or qualitatively incomplete studies have been carried out, but do not make it possible to draw any

Routes of exposure and outcome in the organism

The main routes by which glycol ethers enter the body are via the skin and lungs. The metabolism of glycol ethers depends on the position of the alcohol group on their alkyl chain. Generally, glycol ethers that contain a primary alcohol are metabolised by alcohol dehydrogenase and aldehyde dehydrogenase. The action of these enzymes leads to the formation of alkoxyacids, which are eliminated in the urine. This is the case for ethylene glycol ether derivatives and for the minor β isomers of

Glycol ethers as irritants and acute toxicology

Following brief contact, glycol ethers do not irritate the skin or are only mild irritants. Conversely, all glycol ethers can result in contact dermatitis following repeated exposure and some of them are strong irritants following prolonged cutaneous exposure. Due to the low volatility of these solvents, systemic intoxication following inhalation is rarely severe. At saturating vapour concentrations, signs of irritation of the ocular mucosa and respiratory tract appear. Intoxications via the

Haematotoxic and immunotoxic effects

Haemolysis is one of the signs of the haematological toxicity of certain glycol ethers. A haemolytic effect is observed in laboratory animals following exposure to EGBE, EGPhE, EGnPE, EGiPE and DEGBE. In humans, haemolysis is moderate and has only been observed following the accidental ingestion of EGBE. Some ethylene glycol ether derivatives (EGME, EGEE, DEGDME, EGnPE) can cause medullary hypoplasia, which is often accompanied by leukopenia, neutropenia and non-regenerative anaemia. The

Effects on reproduction

In 1979, the deleterious effects of some glycol ethers on testicular function were demonstrated for the first time in mammals (Nagano et al., 1979). Numerous studies have since confirmed these observations and highlighted the fact that the testicle is highly sensitive to some glycol ethers (particularly EGME, EGEE and DEGDME) and the specificity of the resulting lesions. The germ line cells are the targets of these glycol ethers, which lead to an interruption of spermatogenesis. Testicular

Effects on development

Numerous studies on animals have reported the deleterious effects of certain glycol ethers on development (toxicity during pregnancy, foetal mortality, foetal malformations). EGME and EGEE have proven foetotoxic and teratogenic effects, whereas EGBE only appears to have a foetotoxic effect. American studies carried out on female semi-conductor workers have shown that exposure to photoresists and developer solvents, the major component of which is ethylene-based glycol ethers (mainly EGME and

Cancer

Although most glycol ethers are not genotoxic, experimental data show that some of them are genotoxic in vitro (EGBE, EGEE, EGME, DEGME) and in vivo (EGME, DEGME). EGEE does not seem to have a carcinogenic effect in animals, whereas EGBE appears to lead to the formation of haemangiosarcomas in male but not in female mice, and to the formation of fore-stomach tumours in female but not in male mice. Few studies have looked at the carcinogenic effects of glycol ethers on humans. The few

Conclusions and recommendations

Most interpretable results concerning the potential effects of glycol ethers on biological systems and on health involve substances that are already subjected to domestic usage restrictions (EGME, EGEE and their acetates). Full results are available for EGBE and demonstrate that it does not affect all of the functions studied in the same manner. For other ethylene glycol ether derivatives, the results are still incomplete. Propylene glycol ether derivatives do not seem to have any major

References (2)

  • Ethers de Glycols: Quels Risques Pour la Santé?

    (1999)
  • K. Nagano et al.

    Testicular atrophy of mice induced by ethylene glycol mono alkyl ethers

    Sangyo Igaku

    (1979)

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