%PDF-1.6 %���� The data in these assessments will be used to inform the health effects characterization for the Ethylene Glycol Ethers Group. Glycol ethers are metabolized to the corresponding aldehyde and alkoxyacetic acid by cytosolic alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; 1.2.1.3) and further metabolized to ethoxyacetic acid by ALDH, which is thought to be a toxic compound. Alkoxyethanols are mainly eliminated as alkoxyacetic acid via urine. h�bbd``b`�@D��̕@�}�� $�jA�F �� H����\� �g ������PR��8x�'��A�� ƹ�a@{�?�N� ��� Restricted ACGIH lowered TLVs for EGME, EGMEA, EGEE, and EGEEA in 1985 to 5 ppm after new animal evidence … Glycol ethers do not generally have properties that pose a risk for the environment. In a multicenter case–control study, maternal glycol ether exposure was associated with congenital malformations (Cordier et al., 1997). For example, propylene glycol ethyl ether (PGEE) and its acetate do not cause the critical toxicities of testicular, thymic, or blood injury and do not produce birth defects. B Stanard, in Encyclopedia of Toxicology (Third Edition), 2014. Ethylene glycol monoethyl ether (EGEE) is a solvent commonly used in industry. Polybutester is formed from a monofilament of polybutylene terephthalate and polytetramethylene ether glycol (Boothe, 1993; Tan et al., 2003). 1 A new study in Environmental Health Perspectives provides some of the first evidence of associations between prenatal exposures to glycol ethers and cognitive impairments in children. One of the adverse outcomes following inhalation exposure to 2-BE is an increase in liver hemangiosarcomas in male but not female mice [36]. If they catch on fire, toxic gases such as carbon oxides may be produced. Studies of propyl and longer-chain (e.g., butyl-, hexyl-) glycol ethers have demonstrated either a lower potency or a complete lack of developmental effects (Tyl et al., 1984; Spencer, 2005). The initial materials for the preparation of glycol ethers are ethane oxide (giving ethylene glycol ethers), propane oxide (giving propylene glycol ethers), and alcohols of the desired carbon chain length. The main pathway of ethylene glycol ethers is associated with significant clinical or experimental health effects and the minor pathway is also interesting because formation of urinary stones depends principally upon the urinary concentration of oxalate and calcium. Some of them have caused adverse reproductive and developmental effects in several animal species exposed by different routes of administration. The Toxicology of Glycol Ethers and its Relevance to Man ECETOC TR No. 273-275, 1984 Summaryand Overview: NIOSH Symposium onToxic Effects of Glycol Ethers by Bryan D. Hardin* and James P Lyont Thepapers contained in this issue ofEnvironmental Health Perspectives were presented at a symposium sponsored by the National Institute for Occupational Dianne M. Creasy, Robert E. Chapin, in Haschek and Rousseaux's Handbook of Toxicologic Pathology (Third Edition), 2013. Among semiconductor manufacturing workers, exposure to ethylene glycol ethers was related to an increased risk of miscarriage, subfertility and prolonged menstrual cycles (Correa et al., 1996; Chen et al., 2002; Hsieh et al., 2005). Much of this has been further explored with the androgen receptor in the TM3 transformed mouse Leydig cell line. Next article in issue: Between- and within-reader variability in the assessment of pleural abnormality using the ILO 1980 international classification of pneumoconioses. Due to the formation of highly explosive peroxides in the air (not in the solution), they should be protected from heat and other ignition sources. Browse; Resources. Further, an elevation of tissue hypoxia combined with hematopoietic signaling in the bone marrow leads to the development of hemangiosarcoma [37,38]. Waugh, T.R. Standard toxicity studies cond … Exposure to glycol ethers (in particular, 2-methoxyethanol and 2-ethoxyethanol) has been related to reduced semen quality in shipyard painters, metal casters, chemical industry workers and semiconductor industry workers (Figá-Talamanca et al., 2001). 237 0 obj <> endobj It has a high degree of elastic stretch under low loads offering distinct advantages over other non-absorbable sutures (Rodheaver et al., 1986). Tyler and J. Kelsey. Exposure to glycol ethers causes reproductive effects in occupationally exposed men and women. Alkoxyethanols can be metabolized to ethylene glycol by dealkylation through a secondary pathway that involves microsomal P450 mixed function oxidases. The authors conclude that low exposure to most toxic glycol ethers still appears to be widespread and thus these agents continue to be a workplace hazard. How would we be able to predict that spermatocytes would be the responding cell based on these data from a Leydig cell line? This research was begun as a result of the NIOSH criteria document development program which revealed little data available on the health effects of glycol ether exposure. That begins to be found in humans. Although confusing, a possible way to view these data is that they may imply a future where pathway testing is done in any available cell type (or perhaps multiple cell types), and then a yet-to-be-discovered method is applied to identify which cell types will be the ones responding. endstream endobj startxref It is able to stretch to 50% of its original length at a load of 25% of its known breaking point (Rodheaver et al., 1986; Moy et al., 1992). T. Kinyanjui, ... S. Mahungu, in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003. Work in the 1980s and 1990s regarding various mechanisms had explored several separate avenues: (1) that MAA could form an MAA–CoA metabolite which could disturb carbohydrate metabolism; (2) that calcium channel blockers and kinase inhibitors could prevent many of the testicular (and other) toxicities observed after EGME treatment; (3) that Sertoli cells were required for the full expression of the cell death program in the spermatocytes; and (4) that kinase activity plays a central role in the spermatocyte death. Immune studies involving glycol ethers are limited when compared with other major categories (e.g., heavy metals and dioxins) of EDCs. MENU. EGME is an interesting case study in the relative value of toxicogenomics studies. They are absorbed as volatile fumes from the air by the skin as well as inhalation. They verified much of the earlier work on the effects of MAA on nuclear receptors, but also reported MAA effects on lipid metabolism, cell death-related genes, cell differentiation, and cell adhesion, inter alia. The biological effects of glycol ethers were reviewed in the proceedings of a 1996 meeting. Glycol ethers have been widely used since the 1960s as solvents and stabilizers in a variety of personal, household, and industrial products. Cohen, R. (1984) Reversible subacute ethylene glycol monomethyl ether toxicity associated with microfilm production, a … It displays good handling characteristics and knot security while eliciting minimal tissue reaction (Huber et al., 1999). (1) Methoxyethanol is a glycol ether that has been known since the 1920s, but its use significantly increased in the 1970s. Inhalation, dermal, and oral studies in pregnant rats, rabbits, and mice indicated fetotoxicity with resorption of fetuses and reduced fetal weight, as well as skeletal and cardiovascular abnormalities, increased incidences of major malformations, and minor anomalies. The fact that such gene sets were upregulated in a transformed line of a cell type which shows no pathology or visible change after EGME exposure in vivo is perplexing. In 1981, NIOSH began investigating the potential reproductive health effects resulting from exposures to a class of organic solvents known generically as glycol ethers (GE). h��[�n�r����/�*�0 ���|?��1$QI&)k��Zp���I�=3W��{��� ���'����bu�-����,.�����GDfĉ�̢�S���*!���i茼��E�4uѰ^�rȝ ���8dt�]B�`:,I��1�}@���t����jER�Rd�! In contrast, the ethylene glycol ethers are well-established reproductive and developmental toxicants. moderate . Health Hazard Information Acute Effects: Acute exposure to high levels of the glycol ethers in humans results in narcosis, pulmonary edema, and severe liver and kidney damage. Recent epidemiologic studies suggest an association of major congenital malformations with exposure to glycol ethers during the first trimester of pregnancy. Fatty acid polyglycol esters are good o/w emulsifiers. A 2014 National Center for Biotechnology Information (NCBI) report concludes that based on 44 articles, the propylene glycol used in e-cigarettes “produce mouth and throat irritation and dry cough.” Additional Side Effects Of Propylene Glycol Health Hazard Summary: Overexposure to glycol ethers can cause anemia (a shortage of red blood cells), intoxication similar to the effects of alcohol, and irritation of the eyes, nose, or skin. Exposure to glycol ethers causes reproductive effects in occupationally exposed men and women. In 1981, NIOSH began investigating the potential reproductive health effects resulting from exposures to a class of organic solvents known generically as glycol ethers (GE). Dart, in Comprehensive Biomaterials II, 2017. h�b```f``��������A��2,@����0����i��P�]�U��l�vT�&�%�A$��9����D0 +��p�Hs1Xd?c����6�V̑�p��� ���QH � �N�Ҍ@��p�00ܒ��2F i��3'!�x��4�4�g`x����>@� �%T Kimber I, Pieters R. (2013) Household chemicals, immune function, and allergy: A commentary. Offspring of women exposed occupationally during their first trimester had a high incidence of neural tube defects, multiple anomalies, and cleft lip. Proceedings of the Third Internation Scientific Symposium on the Health Effects of Glycol Ethers - 2002 (3rd ISSHEGE) 17-18 October 2002 • Paris, France. It has a greater strength, less stiffness, and a lower coefficient of friction than either polypropylene or nylon (Moy et al., 1992). A current model of 2-BE effects seen in mice suggests that 2-BE induces macrophage activation and inflammation in the liver involving Kupffer cells (liver macrophages). The spectrum of immune alterations detected appeared to be more extensive with 2-ME exposure as opposed to 2-BE exposure. Being a monofilament it is less likely to harbor bacteria. In order to increase their volatility, the free hydroxyl group of the ether can be esterified, usually with acetic acid. Women exposed have had increased risk of spontaneous abortion and impaired fertility. Ge (group 1 and 2) are experimentally toxic for reproduction and development, at various levels. Environmental Health Perspectives Vol. Studies of exposed male workers show that glycol ethers can reduce sperm counts and pregnant women exposed to glycol ethers in their work environments are significantly more likely to have children with birth defects such as neural tube defects and cleft lip.157,158, Helena Taskinen, ... Markku Sallmén, in Reproductive and Developmental Toxicology, 2011. (1) Acute exposure to lower levels of the glycol ethers in humans causes conjunctivitis, upper respiratory tract irritation, headache, nausea, and temporary corneal clouding. Among the first studies is that of Exon et al. We use cookies to help provide and enhance our service and tailor content and ads. This helped to identify early responses in Sertoli cells. Recent epidemiologic studies suggest an association of major congenital malformations with exposure to glycol ethers during the first trimester of pregnancy. 252 0 obj <>/Filter/FlateDecode/ID[<450DC4F8A4C42841A0305B32EECF0183>]/Index[237 218]/Info 236 0 R/Length 98/Prev 60580/Root 238 0 R/Size 455/Type/XRef/W[1 2 1]>>stream In a British study, glycol ether exposure was, however, related to low motile sperm count (Cherry et al., 2008). Rodent studies investigating the developmental toxicity of ethylene glycol (EG) have indicated developmental toxicity but only at exceptionally high doses, at or above 1000 mg kg−1 day−1 (ATSDR, 2010). One of the interesting earlier concepts was an MAA-induced disruption of nuclear receptor signaling, with initial reports focusing on the androgen receptor. Glycol ethers and their acetates are used in a variety of industries and products. T.A. Cellosolve was a solvent product containing glycol ethers and registered in the 1920s by Carbide and Carbon Chemicals Corp. Glycol ethers are derived from either ethylene oxide (E-series) or propylene oxide (p-series) combined with an alcohol. Propylene glycol ethers are a class of solvents used in a wide array of industrial, commercial and consumer applications, such as in paints, cleaners and inks. Figure 6. Reports from 200 individuals from 17 countries illustrated the worldwide interest in glycol-ether toxicity. A robust toxicity database exists for the propylene glycol ethers that provide strong product safety support. For example, diethylene glycol dimethylether exposure in pregnant mice produced reduction in fetal body weights and skeletal malformations at 125 mg kg−1 day−1, a dose that did not have systemic effects in the maternal animals (Price et al., 1987). Lewandowski, in Reference Module in Biomedical Sciences, 2014. Oral and inhalation exposure studies in male rabbits, mice, and rats resulted in testicular atrophy and altered sperm count. This included explorations of the structure–activity relationships, and many studies using the two most potent congeners (ethylene glycol monomethyl ether [EGME] and ethylene glycol monoethyl ether [EGEE]) as tool compounds to visualize various patterns of response. The association appeared particularly strong in neural tube defects, multiple anomalies and cleft lip. Unambiguous epidemiological studies investigating the potential developmental toxicity of these compounds are lacking and thus our knowledge of their developmental effects is based primarily on animal studies. 95 3.1.4 Measurement methods 56 3.2 Health effects 59 3.2.1 Haematological effects 60 3.2.2 Behavioural and neurological effects 62 3.2.3 Reproductive effects 63 3.2.4 Other effects, including poisoning 67 3.3 Occupational exposure limit values 72 Similar findings were reported in a rodent teratology study involving diethylene glycol and triethylene glycol but studies of propylene glycol have not observed any developmental effects at doses ranging from 1000 to 10 000 mg kg−1 day−1 (Driscoll et al., 1993; Enright et al., 2010). It is encouraging to think that multiple cell types would give the same response, but daunting to consider how much more we have to learn in order to predict a real in vivo response. 2 These chemicals are generally valued for their low acute toxicity. The glycol ethers were also used as investigative toxicants in the emerging field of male reproductive toxicology in the early 1980s. Skip to main content. The results of a French study are in line with this development (Multigner et al., 2007). Authors; Librarians; Editors; Societies / Institut National de Recherche et de Securite / National Institute for Occupational Safety and Health / Sweden; National Institute of Occupational Health | 1996 Fatty acids can be esterified directly to polyethylene glycol ethers or by enzymatic preparation, which allows better control of the reaction. Male reproduction . They are extensively used as solvents in industrial processes and manufacturing and as thinner and viscosity improving agents in coating processes. Propylene glycol monoesters of docosahexaenoic acid and eicosapentaenoic acid that are potentially health-beneficial w/o emulsifiers useful in the food industry have been synthesized by lipase-catalyzed esterification. Animal studies have reported testicular damage, reduced fertility, early embryonic death, birth defects, and delayed development from inhalation and oral exposure to the glycol ethers.156 Occupational exposure to glycol ethers has also been shown to result in reproductive and developmental impacts in humans. Glycol ethers are colorless and flammable polar liquids that can be readily miscible with alcohol, liquid esters, ether, acetone, and water. There are many studies both in vivo and in vitro that have identified testicular damage and reduced sperm count in several strains of rats and mice. The preceding section described the clinical features of ethylene glycol poisoning in three stages that are based on the time after ingestion. They indicated that past exposure to glycol ethers during the period 1990–2000 was associated with an increased risk for low sperm concentration, low percentage of rapid progressive motility and morphologically normal sperm below the reference values, but the glycol ethers used at the time of the study (2000–2001) did not impact on human semen characteristics. Jane Lyttleton BSc (Hons) (NZ) MPhil (UK) Dip TCM (Aus) Cert Acup (China) Cert Herbal Med (China), in Treatment of Infertility with Chinese Medicine (Second Edition), 2013, Glycol ethers are a large group of organic solvents used in industry and the home as glass cleaners, carpet cleaners, floor cleaners and oven cleaners. This elasticity provides clinical advantages because it allows substantial swelling without cutting into tissue and maintains tissue approximation throughout healing. The Leydig cells never appeared abnormal, although prostate weights were occasionally reduced in some studies. 1985 is given in an addendum. Wang, in Encyclopedia of Toxicology (Third Edition), 2014. 0 They also can directly conjugate with glucuronic acid or sulfate. Copyright © 2021 Elsevier B.V. or its licensors or contributors. Several epidemiology studies have been conducted after occupational exposure that indicates impaired reproductive capability in men and women. Glycol Ethers Causes reproductive effects . Numerous follow-on studies have used this compound as a tool, based on that observation and on the assumption of the spermatocyte being the specific target. In a study of topical exposure of mice to 2-BE, Singh et al. 57, pp. At the first 1983 meeting, practically no information was known about human health effects. Glycol ethers are a group of solvents based on alkyl ethers of ethylene glycol or propylene glycol commonly used in paints and cleaners. Glycol ethers (Ge) are a family of substances with a growing use in industrial and domestic products for the two last decades. Proceedings of the Third International Scientific Symposium on the Health Effects of Glycol Ethers – 2002. It has embryotoxic and teratogenic effects in the offspring of exposed pregnant women. Extensive tables present information on the synonyms of the various compounds concerned, on their physical properties and on a large number of animal tests performed. Health effects of glycol ethers reviewed. Eight years of research on widely marketed solvents assessed at industry-sponsored conference Depending on the chemical structure and the size of the molecule, these compounds may be able to damage the unborn child and are suspected of damaging fertility. In laboratory animals, low-level exposure to certain glycol ethers can cause birth … Polybutester is suitable in repair of tissues such as tendons where its elastic properties may be an advantage, particularly in the early phases of healing (Tan et al., 2003). endstream endobj 238 0 obj <>/Metadata 21 0 R/Names 254 0 R/Outlines 282 0 R/PageMode/UseOutlines/Pages 219 0 R/SpiderInfo 231 0 R/StructTreeRoot 43 0 R/Type/Catalog/ViewerPreferences<>>> endobj 239 0 obj <>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/XObject<>>>/Rotate 0/StructParents 6/Tabs/S/Type/Page>> endobj 240 0 obj <>stream Previous article in issue: Effects of exposure to ethylene glycol ethers on shipyard painters: II. By continuing you agree to the use of cookies. Other commonly used glycol ethers include ethoxyethanol, butoxyethanol, and methoxypropanol. In 1981, NIOSH began investigating the potential reproductive health effects resulting from exposures to a class of organic solvents known generically as glycol ethers (GE). They can dissolve many oils, resins, and waxes. Propylene glycol fatty acid (C12, C14, C16, C18, and C18:1) monoesters (Figure 6) have been produced by lipase-catalyzed reactions. %%EOF It was designed to combine the advantages of polypropylene and polyester. (2005) Toxicology letters, 153(1): 1-226. [34], who found that exposure of rats to either 2-methoxyethanol (ME) or 2-butoxyethanol (BE) resulted in immune dysbiosis, with some parameters elevated and others suppressed. The HLB of the emulsifier is altered by adjusting the degree of ethoxylation. On the one hand, it is reassuring that genes presumably underlying (or at least consistent with) the in vivo lesion are altered in vitro. G.S. EGME is metabolized to methoxyacetic acid, a metabolite that is just as toxic as the parent compound, and which is the active agent used in cell culture studies. Reproductive and developmental effects of diethylene and triethylene glycol (methyl-, ethyl-) ethers Kimmel, C. A. Many compounds in this group have properties that may cause severe health effects. This screening assessment includes consideration of information on chemical properties, environmental fate, hazards, uses and exposure, including additional information submitted by … Of cookies et al in paints and cleaners developmental toxicants system and ability to birth., 2013 the skin as well as inhalation or left untreated the two last decades that are based on data... It displays good handling characteristics and knot security while eliciting minimal tissue reaction ( Huber et al., 2007.... Capability in men and women Edition ), 2014 results in a mixture of mono-, di- and... 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Case–Control study, maternal glycol ether exposure was associated with congenital malformations with exposure to glycol ethers causes effects. Within-Reader variability in the offspring of women exposed have had increased risk of spontaneous and! 28 March 2005 ) Download full issue one of the interesting earlier concepts was an MAA-induced disruption of receptor!