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glycol ethers 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. 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). In a study of topical exposure of mice to 2-BE, Singh et al. This helped to identify early responses in Sertoli cells. endstream endobj startxref Kimber I, Pieters R. (2013) Household chemicals, immune function, and allergy: A commentary. It was designed to combine the advantages of polypropylene and polyester. The toxicity of some additional glycol ethers is reviewed in an appendix. Recent epidemiologic studies suggest an association of major congenital malformations with exposure to glycol ethers during the first trimester of pregnancy. Many compounds in this group have properties that may cause severe health effects. Glycol ethers have several applications in industry as lubricants, colorants, and plasticizers. 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. Figure 6. A robust toxicity database exists for the propylene glycol ethers that provide strong product safety support. Several epidemiology studies have been conducted after occupational exposure that indicates impaired reproductive capability in men and women. 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 The Toxicology of Glycol Ethers and its Relevance to Man ECETOC TR No. Glycol Ethers Causes reproductive effects . h�bbd``b`�@D��̕@�}�� $�jA�F �� H����\� �g ������PR��8x�'��A�� ƹ�a@{�?�N� ��� Environmental Health Perspectives Vol. Waugh, T.R. Women exposed have had increased risk of spontaneous abortion and impaired fertility. Recent epidemiologic studies suggest an association of major congenital malformations with exposure to glycol ethers during the first trimester of pregnancy. Glycol ethers may be used in any food-related application (such as coatings or printing inks) without regard to specific FDA regulations if subsequent processing steps, such as washing, drying, vaporizing, heating, purging, etc., are adequate to completely remove all traces of the solvent. 2 These chemicals are generally valued for their low acute toxicity. %%EOF 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). How would we be able to predict that spermatocytes would be the responding cell based on these data from a Leydig cell line? In laboratory animals, low-level exposure to certain glycol ethers can cause birth … It has embryotoxic and teratogenic effects in the offspring of exposed pregnant women. Alkoxyethanols can be metabolized to ethylene glycol by dealkylation through a secondary pathway that involves microsomal P450 mixed function oxidases. Some of them have caused adverse reproductive and developmental effects in several animal species exposed by different routes of administration. 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). 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 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. From: Treatment of Infertility with Chinese Medicine (Second Edition), 2013, A. Shafiee, ... H. Nadri, in Encyclopedia of Toxicology (Third Edition), 2014. [35] found that suppression of T cell activity (but not B cell function) was evident following a 4-day exposure regimen. Ethoxyacetic acid can be further metabolized to carbon dioxide by O-deethylation or glycine conjugated analogs. The spectrum of immune alterations detected appeared to be more extensive with 2-ME exposure as opposed to 2-BE exposure. 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 Glycol ethers (Ge) are a family of substances with a growing use in industrial and domestic products for the two last decades. The biological effects of glycol ethers were reviewed in the proceedings of a 1996 meeting. At the first 1983 meeting, practically no information was known about human health effects. The results of a French study are in line with this development (Multigner et al., 2007). In contrast, the ethylene glycol ethers are well-established reproductive and developmental toxicants. Skip to main content. 454 0 obj <>stream Standard toxicity studies cond … NIOSH Pocket Guide to Chemical Hazards - Centers for Disease Control and Prevention (CDC) ... Glycol Ethers Impurity: ETHYLENE OXIDE Known to cause reproductive toxicity (to females) ... compared to other product formulations. Immune studies involving glycol ethers are limited when compared with other major categories (e.g., heavy metals and dioxins) of EDCs. 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 Numerous pathogenesis studies identified the early and late pachytene spermatocytes (but not mid pachytene spermatocytes) and the dividing spermatocyte as the most sensitive germ cell for this family of toxicants, with cell death being stage-specific and occurring within 12 hours of a single dose. Offspring of women exposed occupationally during their first trimester had a high incidence of neural tube defects, multiple anomalies, and cleft lip. 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. This elasticity provides clinical advantages because it allows substantial swelling without cutting into tissue and maintains tissue approximation throughout healing. MENU. T. Kinyanjui, ... S. Mahungu, in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003. Alkoxyethanols are mainly eliminated as alkoxyacetic acid via urine. Fatty acid polyglycol esters are good o/w emulsifiers. The data in these assessments will be used to inform the health effects characterization for the Ethylene Glycol Ethers Group. Glycol ethers and their acetates are used in a variety of industries and products. Glycol ethers are colorless and flammable polar liquids that can be readily miscible with alcohol, liquid esters, ether, acetone, and water. 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 glycols (alkyl diols) and glycol ethers are widely used industrial chemicals. Dart, C.M. Tyler and J. Kelsey. Alkoxyacetic acid is responsible for reproductive and developmental toxic effects of alkoxyethanols. Maureen Paul, Sabrina Kurtz, Analysis of reproductive health hazard information on material safety data sheets for lead and the ethylene glycol ethers, American Journal of Industrial Medicine, 10.1002/ajim.4700250308, 25, 3, (403-415), (2007). Other propylene glycol ethers also exhibit a similar lack of toxicity. 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. The glycol ethers were also used as investigative toxicants in the emerging field of male reproductive toxicology in the early 1980s. Previous article in issue: Effects of exposure to ethylene glycol ethers on shipyard painters: II. 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 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�! ----- EPA/540/1-86-052 September 1984 HEALTH EFFECTS ASSESSMENT FOR GLYCOL ETHERS U.S. Environmental Protection Agency Office of Research and Development Office of Health and Environmental Assessment Environmental Criteria and Assessment Office Cincinnati, OH 45268 U.S. Environmental Protection Agency Office of Emergency and Remedial Response Office of Solid Waste … / Institut National de Recherche et de Securite / National Institute for Occupational Safety and Health / Sweden; National Institute of Occupational Health | 1996 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). T.A. describe the physiologic effects of ethylene glycol poisoning. Use of methoxyethanol has declined in recent years due to risk management procedures and replacement by other substances. Restricted ACGIH lowered TLVs for EGME, EGMEA, EGEE, and EGEEA in 1985 to 5 ppm after new animal evidence … 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. Ethylene Glycol Ethers Group - information sheet - Oral and inhalation exposure studies in male rabbits, mice, and rats resulted in testicular atrophy and altered sperm count. (2005) Toxicology letters, 153(1): 1-226. 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 use of the most toxic glycol ethers has decreased from the mid-1990s and has gradually been replaced with less toxic long chain glycol ethers and propylene glycol ethers. In a British study, glycol ether exposure was, however, related to low motile sperm count (Cherry et al., 2008). Dart, in Comprehensive Biomaterials II, 2017. Methoxyethanol is a glycol ether that has been known since the 1920s, but its use significantly increased in the 1970s. Exposure to glycol ethers causes reproductive effects in occupationally exposed men and women. [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. (1) Acute exposure to lower levels of the glycol ethers in humans causes conjunctivitis, upper respiratory tract irritation, headache, nausea, and temporary corneal clouding. Propylene glycol esters of fatty acids, where R1 and R2 represent a fatty acid and/or a hydrogen, and where at least one R represents a fatty acid. 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). Much of this has been further explored with the androgen receptor in the TM3 transformed mouse Leydig cell line. 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. 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). Cohen, R. (1984) Reversible subacute ethylene glycol monomethyl ether toxicity associated with microfilm production, a … 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). The entire class of glycol ethers is well documented for their effects on the male reproductive system and ability to cause birth defects. They are extensively used as solvents in industrial processes and manufacturing and as thinner and viscosity improving agents in coating processes. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, Treatment of Infertility with Chinese Medicine (Second Edition), 2013, Encyclopedia of Toxicology (Third Edition), 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), Occupational exposure to chemicals and reproductive health, Reproductive and Developmental Toxicology, Haschek and Rousseaux's Handbook of Toxicologic Pathology (Third Edition), Effects of Endocrine Disrupters on Immune Function and Inflammation, Developmental and Reproductive Toxicology, Encyclopedia of Food Sciences and Nutrition (Second Edition), Fatty acids can be esterified directly to polyethylene, Handbook of Toxicologic Pathology (Second Edition), Fundamentals of Air Pollution (Fourth Edition), Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics. Further, an elevation of tissue hypoxia combined with hematopoietic signaling in the bone marrow leads to the development of hemangiosarcoma [37,38]. The association appeared particularly strong in neural tube defects, multiple anomalies and cleft lip. B Stanard, in Encyclopedia of Toxicology (Third Edition), 2014. The other thing this calls into question is the current common practice of linking gene response data from affected cells to the lesions in those cells. 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. Previous vol/issue. The reaction always results in a mixture of mono-, di-, and triglycol ethers, which are then distilled to the required purity. 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. 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. If they catch on fire, toxic gases such as carbon oxides may be produced. Investigators could differentiate gene responses into different classes based on how MAA interacted with applied testosterone. The Glycol Ethers, with Particular Reference to 2-Methoxyethanol and 2-Ethoxyethanol: Evidence of Adverse Reproductive Effects The National Institute for Occupational Safety and Health (NIOSH) recommends that 2-methoxyethanol (2ME) and 2-ethoxyethanol (2EE) be regarded in the workplace as having the potential to cause adverse reproductive effects in male and female workers. G.S. A.J. They are absorbed as volatile fumes from the air by the skin as well as inhalation. 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. 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. Proceedings of the Third International Scientific Symposium on the Health Effects of Glycol Ethers – 2002. Lewandowski, in Reference Module in Biomedical Sciences, 2014. 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. 0 The Leydig cells never appeared abnormal, although prostate weights were occasionally reduced in some studies. 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. One of the interesting earlier concepts was an MAA-induced disruption of nuclear receptor signaling, with initial reports focusing on the androgen receptor. Starek, A., Szymczak, W. and Zapór, L. (2008) Hematological effects of four ethylene glycol monoalkyl ethers in short-term repeated exposure in rats. On the other hand, for these to be changed in an unaffected cell type calls into question our ability to predict what the response would be in an animal (human or rodent) after such an exposure. It displays good handling characteristics and knot security while eliciting minimal tissue reaction (Huber et al., 1999). Archives of Toxicology, 82(2), 125-136. Ge (group 1 and 2) are experimentally toxic for reproduction and development, at various levels. Health effects of glycol ethers reviewed. It has a high degree of elastic stretch under low loads offering distinct advantages over other non-absorbable sutures (Rodheaver et al., 1986). 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. Subsequent work on this and another short-chain fatty acid (valproic acid) found early and specific dysregulation of multiple nuclear receptors through activating the mitogen-activated protein kinase (MAPK) and inhibiting histone deacetylase, although neither were sufficient to account for all the receptor-potentiating effects reported for MAA. 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. %PDF-1.6 %���� In a multicenter case–control study, maternal glycol ether exposure was associated with congenital malformations (Cordier et al., 1997). (1) 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. Polybutester is formed from a monofilament of polybutylene terephthalate and polytetramethylene ether glycol (Boothe, 1993; Tan et al., 2003). They can dissolve many oils, resins, and waxes. On the one hand, it is reassuring that genes presumably underlying (or at least consistent with) the in vivo lesion are altered in vitro. Glycol ethers do not generally have properties that pose a risk for the environment. 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. Reports from 200 individuals from 17 countries illustrated the worldwide interest in glycol-ether toxicity. One of the adverse outcomes following inhalation exposure to 2-BE is an increase in liver hemangiosarcomas in male but not female mice [36]. 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). We use cookies to help provide and enhance our service and tailor content and ads. 237 0 obj <> endobj In those studies where developmental effects were noted, significant maternal toxicity was also observed at or near the dose associated with developmental toxicity, suggesting that EG is at most only slight more toxic to the developing organism than the adult animal.

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