Epoxy compounds are those that consist of oxirane rings (either one or more). An oxirane ring is essentially one oxygen atom linked to two carbon atoms. These will react with amino, hydroxyl and carboxyl groups as well as inorganic acids to yield relatively stable compounds.
Uses
Epoxy compounds have found wide industrial use as chemical intermediates in the manufacture of solvents, plasticizers, cements, adhesives and synthetic resins. They are commonly used in various industries as protective coatings for metal and wood. The alpha-epoxy compounds, with the epoxy group (C-O-C) in the 1,2 position, are the most reactive of the epoxy compounds and are primarily used in industrial applications. The epoxy resins, when converted by curing agents, yield highly versatile, thermosetting materials used in a variety of applications including surface coatings, electronics (potting compounds), laminating, and bonding together of a wide variety of materials.
Butylene oxides (1,2-epoxybutane and 2,3-epoxybutane) are used for the production of butylene glycols and their derivatives, as well as for the manufacture of surface active agents. Epichlorohydrin is a chemical intermediate, insecticide, fumigant and solvent for paints, varnishes, nail enamels and lacquers. It is also used in polymer coating material in the water supply system and in raw material for high wet-strength resins for the paper industry. Glycidol (or 2,3-epoxypropanol) is a stabilizer for natural oils and vinyl polymers, a dye-leveling agent and an emulsifier.
1,2,3,4-Diepoxybutane. Short-term (4-hour) inhalation studies with rats have caused watering of the eyes, clouding of the cornea, laboured breathing and lung congestion. Experiments in other animal species have demonstrated that diepoxybutane, like many of the other epoxy compounds, can cause eye irritation, burns and blisters of the skin, and irritation of the pulmonary system. In humans, accidental “minor” exposure caused swelling of the eyelids, upper respiratory tract irritation, and painful eye irritation 6 hours after exposure.
Skin application of D,L- and the meso- forms of 1,2,3,4-diepoxybutane have produced skin tumours, including squamous-cell skin carcinomas, in mice. The D- and L- isomers have produced local sarcomas in mice and rats by subcutaneous and intraperitoneal injection respectively.
Several epoxy compounds are employed in the health care and food industries. Ethylene oxide is used to sterilize surgical instruments and hospital equipment, fabric, paper products, sheets and grooming instruments. It is also a fumigant for foodstuffs and textiles, a rocket propellant, and a growth accelerator for tobacco leaves. Ethylene oxide is used as an intermediary in the production of ethylene glycol, polyethylene terephthalate polyester film and fibre, and other organic compounds. Guaiacol is a local anaesthetic agent, antioxidant, stimulant expectorant, and a chemical intermediate for other expectorants. It is used as a flavouring agent for non-alcoholic beverages and food. Propylene oxide, or 1,2-epoxypropane, has been used as a fumigant for the sterilization of packaged food products and other materials. It is a highly reactive intermediary in the production of polyether polyols, which, in turn, are used to make polyurethane foams. The chemical is also used in the production of propylene glycol and its derivatives.
Vinylcyclohexene dioxide is used as a reactive diluent for other diepoxides and for resins derived from epichlorohydrin and bisphenol A. Its use as a monomer for the preparation of polyglycols containing free epoxide groups or for polymerization to a tridimensional resin has been investigated.
Furfural is used in screening tests for urine, solvent refining of petroleum oils, and manufacturing of varnishes. It is a synthetic flavouring agent, a solvent for nitrated cotton, a constituent of rubber cements, and a wetting agent in the manufacture of abrasive wheels and brake linings. Furfuryl alcohol is also a flavouring agent, as well as a liquid propellant and solvent for dyes and resins. It is used in corrosive-resistant sealants and cements, and foundry cores. Tetrahydrofuran is used in histology, chemical synthesis, and in the fabrication of articles for packaging, transporting and storing foods. It is a solvent for fat oils and unvulcanized rubber. Diepoxybutane has been used to prevent spoilage of foodstuffs, as a polymer curing agent, and for cross-linking textile fibres.
Hazards
There are numerous epoxy compounds in use today. Specific commonly used ones are individually discussed below. There are, however, certain characteristic hazards shared by the group. In general, the toxicity of a resin system is a complicated interplay between the individual toxicities of its various component ingredients. The compounds are known sensitizers of the skin, and those with the highest sensitization potential are those of lower relative molecular weight. Low molecular weight is also generally associated with increased volatility. Delayed and immediate allergic epoxy dermatitis and irritant epoxy dermatitis have all been reported. The dermatitis usually first develops on the hands between the digits, and can range in severity from erythema to marked bullous eruption. Other target organs reportedly adversely affected by epoxy compound exposure include the central nervous sysstem (CNS), the lungs, the kidneys, the reproductive organs, the blood and the eyes. There is also evidence that certain epoxy compounds have mutagenic potential. In one study, 39 of the 51 epoxy compounds tested induced a positive response in the Ames/Salmonella assay. Other epoxides have been shown to induce sister-chromatid exchanges in human lymphocytes. Animal studies looking at associated epoxide exposures and cancers are ongoing.
It should be noted that certain of the curing agents, hardeners and other processing agents used in the production of the final compounds have associated toxicities as well. One in particular, 4,4-methylenedianiline (MDA), is associated with hepatotoxicity and with damage to the retina of the eye, and has been known to be an animal carcinogen. Another is trimellitic anhydride (TMA). Both are discussed elsewhere in this chapter.
One epoxy compound, epichlorohydrin, has been reported to cause a significant increase of pulmonary cancer in exposed workers. This chemical is classified as a Group 2A chemical, probably carcinogenic to humans, by the International Agency for Research on Cancer (IARC). One long-term epidemiological study of workers exposed to epichlorohydrin at two US facilities of the Shell Chemical Company was reported to demonstrate a statistically significant (p < .05) increase in deaths due to respiratory cancer. Like the other epoxy compounds, epichlorohydrin is irritating to the eyes, skin and respiratory tract of exposed individuals. Human and animal evidence has demonstrated that epichlorohydrin may induce severe skin damage and systemic poisoning following extended dermal contact. Exposures to epichlorohydrin at 40 ppm for 1 h have been reported to cause eye and throat irritation lasting 48 h, and at 20 ppm caused temporary burning of the eyes and nasal passages. Epichlorohydrin-induced sterility in animals has been reported, as have liver and kidney damage.
Subcutaneous injection of epichlorohydrin has produced tumours in mice at the injection site but has not produced tumours in mice by skin-painting assay. Inhalation studies with rats have shown a statistically significant increase in nasal cancer. Epichlorohydrin has induced mutations (base-pair substitution) in microbial species. Increases in the chromosomal aberrations found in the white blood cells of workers exposed to epichlorohydrin have been reported. As of 1996 the American Conference of Governmental Industrial Hygienists (ACGIH) established a TLV of 0.5 ppm, and it is considered an A3 carcinogen (animal carcinogen).
1,2-Epoxybutane and isomers (butylene oxides). These compounds are less volatile and less toxic than propylene oxide. The major documented adverse effects in humans have been irritation of the eyes, nasal passages and skin. In animals, however, respiratory problems, pulmonary haemorrhage, nephrosis and nasal-cavity lesions were noted in acute exposures to very high concentrations of 1,2-epoxybutane. No consistent teratogenic effects have been demonstrated in animals. IARC has determined that there is limited evidence for the carcinogenicity of 1,2-epoxybutane in experimental animals.
When 1,2-epoxypropane (propylene oxide) is compared to ethylene oxide, another epoxy compound commonly used in sterilization of surgical/hospital supplies, propylene oxide is considered to be far less toxic to humans. Exposure to this chemical has been associated with irritant effects on the eyes and skin, respiratory tract irritation, and CNS depression, ataxia, stupor and coma (the latter effects have thus far been significantly demonstrated only in animals). In addition, 1,2-epoxypropane has been shown to act as a direct alkylating agent in various tissues, and thus the possibility of carcinogenic potential is raised. Several animal studies have strongly implicated the compound’s carcinogenicity as well. The major adverse effects which have thus far been definitively demonstrated in humans involve burning or blistering of the skin when prolonged contact with non-volatilized chemical has occurred. This has been shown to occur even with low concentrations of propylene oxide. Corneal burns attributed to the chemical have also been reported.
Vinylcyclohexene dioxide. The irritation produced by the pure compound after application on rabbit skin resembles the oedema and reddening of first-degree burns. Skin application of vinylcyclohexene dioxide in mice produces a carcinogenic effect (squamous-cell carcinomas or sarcomas); intraperitoneal administration in rats caused analogous effects (sarcomas of the peritoneal cavity). The substance has proved to be mutagenic in Salmonella typhimurium TA 100; it also produced a significant increase in mutations in Chinese hamster cells. It should be treated as a substance with carcinogenic potential, and appropriate engineering and hygienic controls should be in place.
In industrial experience vinylcyclohexene dioxide has been shown to have skin irritant properties and to cause dermatitis: a severe vesiculation of both feet has been observed in a worker who had put on shoes contaminated by the compound. Eye injury is also a definite hazard. Studies on chronic effects are not available.
2,3-Epoxypropanol. Based on experimental studies with mice and rats, glycidol was found to cause eye and lung irritation. The LC50 for a 4-h exposure of mice was found to be 450 ppm, and for an 8-h exposure of rats it was 580 ppm. However, at concentrations of 400 ppm of glycidol, rats exposed for 7 h a day for 50 days showed no evidence of systemic toxicity. After the first few exposures, slight eye irritation and respiratory distress were noted.
Ethylene oxide (ETO) is a highly dangerous and toxic chemical. It reacts exothermically and is potentially explosive when heated or placed in contact with alkali metal hydroxides or highly active catalytic surfaces. Therefore when in use in industrial areas it is best if it is tightly controlled and confined to closed or automated processes. The liquid form of ethylene oxide is relatively stable. The vapour form, in concentrations as low as 3%, is very flammable and potentially explosive in the presence of heat or flame.
A wealth of information exists regarding the possible human health effects of this compound. Ethylene oxide is a respiratory, skin and eye irritant. At high concentrations it is also associated with central nervous system depression. Some individuals exposed to high concentrations of the chemical have described a strange taste in their mouths after the exposure. Delayed effects of high acute exposures include headache, nausea, vomiting, shortness of breath, cyanosis and pulmonary oedema. Additional symptoms that have been reported after acute exposures include drowsiness, fatigue, weakness and incoordination. Ethylene oxide solution can cause a characteristic burn on exposed skin anywhere from 1 to 5 h post-exposure. This burn often progresses from vesicles to coalescent blebs and desquamation. The skin wounds will often spontaneously resolve, with increased pigmentation resulting at the burn site.
Chronic or low-to-moderate prolonged exposures to ethylene oxide are associated with mutagenic activity. It is known to act as an alkylating agent in biological systems, binding to the genetic material and other electron-donating sites, such as haemoglobin, and causing mutations and other functional damage. ETO is associated with chromosomal damage. The ability of damaged DNA to repair itself was adversely affected by low but prolonged exposure to ETO in one study of exposed human subjects. Some studies have linked ETO exposure with increased absolute lymphocyte counts in exposed workers; however, recent studies are not supportive of this association.
The carcinogenic potential of ethylene oxide has been demonstrated in several animal models. IARC has classified ethylene oxide as a Group 1 known human carcinogen. Leukaemia, peritoneal mesothelioma and certain brain tumours have been associated with long-term inhalation of ETO in rats and monkeys. Studies of exposure in mice have linked inhalation exposures to lung cancers and lymphomas. Both the US National Institute for Occupational Safety and Health (NIOSH) and the US Occupational Safety and Health Administration (OSHA) have concluded that ethylene oxide is a human carcinogen. The former conducted a large-scale study of over 18,000 ETO-exposed workers over a 16-year period and determined that the exposed individuals had greater than expected rates of blood and lymph cancers. Subsequent studies have found that no increased rates of these cancers have been associated with exposed workers. One of the major problems with these studies, and a possible reason for their contradictory nature, has been the inability to accurately quantify levels of exposure. For example, much of the available research on human carcinogenic effects of ETO has been done using exposed hospital sterilizer operators. Individuals who worked in these jobs prior to the 1970s most likely experienced higher exposures to ETO gas due to the technology and lack of local control measures in place at that time. (Safeguards in the use of ETO in health care settings are discussed in the Health care facilities and services chapter in this volume.)
Ethylene oxide has also been associated with adverse reproductive effects in both animals and humans. Dominant lethal mutations in reproductive cells have resulted in higher embryonic death rates in the offspring of ETO-exposed male and female mice and rats. Some studies have linked ethylene oxide exposure to increased rates of miscarriage in humans.
Adverse neurological and neuropsychiatric effects resulting from ethylene oxide exposure have been reported in animals and humans. Rats, rabbits and monkeys exposed to 357 ppm of ETO over a period of 48 to 85 days developed impairment of sensory and motor function, and muscle wasting and weakness of the hind limbs. One study found that human workers exposed to ETO demonstrated impaired vibratory sense and hypoactive deep tendon reflexes. The evidence of impaired neuropsychiatric functioning in humans exposed to low but prolonged levels of ethylene oxide is uncertain. Some studies and an increasing body of anecdotal evidence suggest that ETO is linked to CNS dysfunction and cognitive impairment—for example, clouded thinking, memory problems and slowed reaction times on certain types of tests.
One study of individuals exposed to ethylene oxide in a hospital setting suggested an association between that exposure and the development of ocular cataracts.
An additional hazard associated with exposure to ethylene oxide is the potential for the formation of ethylene chlorohydrin (2-chloroethanol), which may be formed in the presence of moisture and chloride ions. Ethylene chlorohydrin is a severe systemic poison, and exposure to the vapour has caused human fatalities.
Tetrahydrofuran (THF) forms explosive peroxides when exposed to air. Explosions may also occur when the compound is brought into contact with lithium-aluminium alloys. Its vapour and peroxides may cause irritation of the mucous membranes and skin, and it is a strong narcotic.
While limited data are available on the industrial experiences with THF, it is interesting to note that investigators that were engaged in animal experiments with this compound complained of severe occipital headaches and dullness after each experiment. Animals subjected to lethal doses of tetrahydrofuran fell into narcosis quickly, which was accompanied by muscular hypotonia and disappearance of corneal reflexes, and followed by coma and death. Single toxic doses caused giddiness, irritation of mucous membranes with copious flow of saliva and mucous, vomiting, a marked fall in blood pressure, and muscular relaxation, followed by prolonged sleep. Generally, the animals recovered from these doses and showed no evidence of biological changes. After repeated exposures, the effects included irritation of the mucous membranes, which may be followed by renal and hepatic alteration. Alcoholic beverages enhance the toxic effect.
Safety and Health Measures
The primary purposes of control measures for the epoxy compounds should be to reduce the potential for inhalation and skin contact. Wherever feasible, control at the source of contamination should be implemented with enclosure of the operation and/or the application of local exhaust ventilation. Where such engineering controls are not sufficient to reduce airborne concentrations to acceptable levels, respirators may be necessary to prevent pulmonary irritation and sensitization in exposed workers. Preferred respirators include gas masks with organic vapour cannisters and high-efficiency particulate filters or supplied-air respirators. All body surfaces should be protected against contact with epoxy compounds through the use of gloves, aprons, face shields, goggles and other protective equipment and clothing as necessary. Contaminated clothing should be removed as soon as possible and the affected areas of the skin washed with soap and water.
Safety showers, eyewash fountains and fire extinguishers should be located in areas where appreciable amounts of epoxy compounds are in use. Handwashing facilities, soap and water should be made available to involved employees.
The potential fire hazards associated with epoxy compounds suggest that no flames or other sources of ignition, such as smoking, be permitted in areas where the compounds are stored or handled.
Affected workers should, as necessary, be removed from emergency situations, and if the eyes or skin have been contaminated they should be flushed with water. Contaminated clothing should be promptly removed. If exposure is severe, hospitalization and observation for 72 h for delayed onset of severe pulmonary oedema is advisable.
When the epoxy compounds, such as ethylene oxide, are extremely volatile, stringent safeguards should be taken to prevent fire and explosion. These safeguards should include the control of ignition sources, including static electricity; the availability of foam, carbon dioxide or dry chemical fire extinguishers (if water is used on large fires, the hose should be equipped with a fogging nozzle); the use of steam or hot water to heat ethylene oxide or its mixtures; and storage away from heat and strong oxidizers, strong acids, alkalis, anhydrous chlorides or iron, aluminium or tin, iron oxide, and aluminium oxide.
Proper emergency procedures and protective equipment should be available to deal with spills or leaks of ethylene oxide. In case of a spill, the first step is to evacuate all personnel except those involved in the clean-up operations. All ignition sources in the area should be removed or shut down and the area well ventilated. Small quantities of spilled liquid can be absorbed on cloth or paper and allowed to evaporate in a safe place such as a chemical fume hood. Ethylene oxide should not be allowed to enter a confined space such as a sewer. Workers should not enter confined spaces where ethylene oxide has been stored without following proper operating procedures designed to ensure that toxic or explosive concentrations are not present. Whenever possible, ethylene oxide should be stored and used in closed systems or with adequate local exhaust ventilation.
All substances having carcinogenic properties, such as ethylene oxide and vinylcyclohexene dioxide, must be handled with extreme care to avoid contact with the workers’ skin or being inhaled during both production and use. Prevention of contact is also promoted by designing the work premises and process plant so as to preclude any leakage of the product (application of a slight negative pressure, hermetically sealed process and so on). Precautions are discussed more fully elsewhere in this Encyclopaedia.
Epoxy compounds tables
Table 1 - Chemical information.
Table 2 - Health hazards.
Table 3- Physical and chemical hazards.
Table 4 - Physical and chemical properties.