The INSERM expert review on glycol ethers: findings and recommendations
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)- et al.
Testicular atrophy of mice induced by ethylene glycol mono alkyl ethers
Sangyo Igaku
(1979)
Cited by (35)
Atmospheric degradation of 2-Isopropoxyethanol: Reactions with Cl, OH and NO<inf>3</inf>
2024, Atmospheric EnvironmentHematological variations in healthy participants exposed 2 h to propylene glycol ethers under controlled conditions
2023, Science of the Total EnvironmentBlood absorption toxicokinetics of glycol ethers after inhalation: A human controlled study
2022, Science of the Total EnvironmentCitation Excerpt :Workers and the general population are exposed to both aerosols and vapors generated during application of products containing these chemicals alone or in mixture. The greatest potential for exposure is during surface coating and cleaning (Agence française de sécurité sanitaire de l'environnement et du travail (afsset), 2008; Institut national de recherche et de sécurité, 2011; Multigner et al., 2005). Inhalation exposure is also possible during manufacture or production.
Prenatal exposure to glycol ethers and visual contrast sensitivity in 6-year-old children in the PELAGIE mother-child cohort
2021, International Journal of Hygiene and Environmental HealthCitation Excerpt :GEs from the P series are mainly produced as compounds with a secondary alcohol and are metabolised via O-demethylation and oxidation to carbon dioxide. Their inability to forming alkoxy carboxylic acids is the most likely reason for their low toxicity when compared to GEs from the E series (Multigner et al., 2005). 1PG2ME, together with its acetate, is classified as category 1 B reprotoxicant by the classification, labeling and packaging regulation (CLP) in the European Union.
Exposure to glycol ethers among 6-year-old children in France
2020, International Journal of Hygiene and Environmental Health