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6.1 Epichlorohydrin Health Science and Safety |
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Hazards Health Hazards Summary of human health effects
EPICHLOROHYDRIN HAS BEEN CLINICALLY DEMONSTRATED TO BE A TOXIC, SEVERELY IRRITATING COMPOUND. THE LIQUID CAN BE FATAL IF SWALLOWED. IT CAN CAUSE SEVERE BURNS AND PERMANENT INJURY IF CONTACTED WITH THE SKIN OR EYES. THE VAPORS ARE SEVERELY IRRITATING TO THE EYE, NOSE, THROAT AND LUNGS. REPEATED OR PROLONGED EXPOSURE CAN CAUSE SEVERE AND LASTING LUNG, LIVER, AND KIDNEY INJURY. HIGH CONCENTRATIONS CAN CAUSE DEATH.
Some people become sensitized on exposure to epichlorohydrin and show allergic skin reactions on subsequent exposure to very small quantities. Liquid epichlorohydrin is reported to produce only a slight and transient burning sensation when in first contact with the skin of man. Blistering and deep-seated pain in the contact area, however, may occur several hours after the time of the initial contact. Hypersensitive individuals may develop an allergic-type of dermatitis following over exposure to vapors or following direct contact of the liquid with the skin. The liquid is also highly irritating to the eyes
In statistical studies on groups of persons who have been exposed to ECH, other effects have been to date (through 1979) in an ongoing epidemiology study of ECH workers has been reported by the investigator to show "weak" evidence that exposure to epichlorohydrin poses a cancer risk to man.1 There is also a study which reports possible genetic risk to man as a result of occupational exposure to ECH,2 but a testicular function study of ECH workers indicated no significant differences between exposed and unexposed workers.3 Summary of Toxicological Findings From In-Vitro and In-Vivo Experiments Epichlorohydrin has been reported to cause tumors at the injection site in mice when it was experimentally injected under the skin.4 ECH has been reported to produce nasal cancer in rates exposed for 2 years to 30 ppm in air but not at 10 ppm.5 It was also found to be positive in some mutagenicity assays in bacteria6,7,8 and cultured human cells.9 Established Exposure Limits Several organizations have established exposure limits for the compound; these are summarized in Table 1.
Table 1/Exposure limits for epichlorohydrin established values
aTime wieighted average, 8-hour day/40 hr-work week, unless otherwise noted. bShort term exposure limit, 15 minutes max. cPermissible exposure limits, Occupational Safety and Health Administration (OSHA). dThreshold limit values, American Conference of Governmental Industrial Hygienists (ACGIH) eRecommended exposure standard, National Institute for Occupational Safety and Health (NIOSH). fTime weighted average, 10-hour day/40-hour week.
These low concentrations are not detectable by smell. Therefore,
work-place air monitoring is required to be sure that concentrations are
below adopted levels. If the odor of epichlorohydrin is detected or if
industrial hygiene personnel monitoring indicates that concentrations
exceed established levels, action must be taken at once to avoid exposure.
Employees should be instructed to leave the area or don NIOSH-approved
respiratory equipment. The source of the leak should be eliminated or
sufficient additional exhaust ventilation should be provided to bring
epichlorohydrin concentrations within the compliance level as indicated by
personnel monitoring.
Hazard Ratings
Although it had previously classified ECH as a cancer suspect agent in
1980, the American Conference of Governmental Industrial Hygienists (ACGIH)
removed ECH from its A2 list,11 "Industrial Substances Suspect of Carcinogenic Potential for MAN."
Detailed Information on Acute Experimental Effects
The liquid or vapor is potent eye and skin irritant. It is markedly
irritating when instilled in the eye and intensely irritating to the
depilated skin of laboratory animals leading to widespread necrosis. In
man, contact of the liquid with the skin produces, at first, a slight
transient burning sensation which may be followed several hours later by
blistering and pain in the region of contact.
The dermal LD50 for rabbits has been reported to be 0.88 ml/kg.13
Ingestion of ECH can be fatal. At double the oral LD50 level (0.09 g/kg),
the blood pressure of rats decreased markedly and continuously until the
animals died.13
The only sign of distress following the oral administration of lethal doses
of epichlorohydrin to rats was sluggishness, but deaths occurred within 24
hours. Autopsy findings in the rats consisted largely of congestion of the
lungs, liver, kidneys, and stomach, and congestion and hemorrhages in the
intestines.14
In the same study, hemorrhages and congestion in the lungs were seen in
most rats exposed to lethal concentrations of vapor.
In one rat inhalation study, the concentration that killed 50% of the test
rats ( LC50) was found to be 500 ppm for 4 hours exposure. The exposed
animals showed gradual development of cyanosis followed by muscular
relaxation of the extremities, but not narcosis. Rats exposed repeatedly
to 120 ppm for 6 hour periods showed lung, liver, and kidney injury; some
respiratory distress was observed at 56 ppm, while 9 ppm was reported to
produce no effects.13
Epichlorohydrin produced muscular paralysis and gradual depression of
respiration leading to death after a single 30-minute exposure of mice to
8,300 ppm of vapor, the repeated application of the liquid (0.5 ml/kg) to
the skin of rats, and the repeated oral administration of the liquid (0.1
ml/kg) to mice. Regardless of the route of administration, toxic doses of
epichlorohydrin produced a similar chain of symptoms which differed mainly
in the time of onset. In general, there was gradual development of
cyanosis followed by muscular relaxation of the extremities. These
symptoms developed very slowly and in many instances they were observed for
several days before respiration became markedly depressed prior to death.
Despite depression of respiration and skeletal musculature, a narcotic
state was not observed. Only minor pathological changes consisting mainly
of congestion of the internal organs, were observed on examinations of the
organs of the deceased mice.13
Epichlorohydrin has been shown by animal experiments to be irritating and
systemically toxic by the oral, percutaneous and subcutaneous routes, as
well as by inhalation of the vapor. Death of animals at high dosage levels
is attributed to the action of epichlorohydrin on the central nervous
system, particularly on the respiratory center and/or the respiratory
tract. The cumulative toxicological action of epichlorohydrin is believed
to be due to its nephrotoxic action. Animals show local irritation and
symptoms of systemic intoxication following the absorption of the liquid
through the intact skin.13 |
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