# I. RECOMMENDATIONS FOR AN EPICHLOROHYDRIN STANDARD
The National Institute for Occupational Safety and Health (NIOSH) recommends that employee exposure to epichlorohydrin in the workplace be controlled by adherence to the following sections.
The standard is designed to protect the health and safety of employees for up to a 10-hour workday, 40-hour workweek, over a working lifetime. Compliance with all sections of the standard should prevent adverse effects produced by exposure of employees to epichlorohydrin. Although the workplace environmental limits are considered to be safe levels based on current information, they should be regarded as the upper boundary of exposure, and every effort should be made to maintain exposure as low as is technically feasible.
The standard is measurable by techniques that are available and there is sufficient technology to permit compliance with the recommended standard. The standard will be subject to review and revision as necessary.
These criteria and the recommended standard apply to exposure of employees to solid, liquid, or gaseous 3-chloro-l,2-epoxypropane, hereafter referred to as "epichlorohydrin," either alone or in combination with other substances. Synonyms for epichlorohydrin include l-chloro-2,3epoxypropane, (chloromethyl)ethylene oxide, chloromethyloxirane, chloropropylene oxide, gamma-chloropropylene oxide, 3-chloro-l,2-propylene oxide, 2-chloromethyl-oxirane, alpha-epichlorohydrin, epichlorhydrin, and epichlorophydrin.
"Occupational exposure to epichlorohydrin" is defined as exposure to airborne epichlorohydrin at concentrations exceeding the action level. The 1 "action level" is defined as one-half of the recommended time-weighted average (TWA) environmental concentration for epichlorohydrin. Exposure to airborne epichlorohydrin at concentrations equal to or less than one-half of the workplace environmental limit, as determined in accordance with Section 8, will not require adherence to the following sections except for 2, 3, 4(a), 5(a,b,c,d), 6, and 7. If exposure to other chemicals also occurs, provisions of any applicable standard for the other chemicals shall also be followed. Procedures for sampling and analysis of environmental samples and calibration of equipment shall be as provided in Appendices I and II, or by any methods shown to be at least equivalent, in accuracy, sensitivity, and precision to the methods specified.

# Section -Medical
Medical surveillance shall be made available to all persons subject to occupational exposure to epichlorohydrin as described below:
(a) Preplacement medical examinations shall include:
(1) Comprehensive medical and work histories.
(2) Complete physical examination, giving particular attention to the kidneys, liver, respiratory tract, and hematopoietic system.
Additionally, employees shall be evaluated for complaints and evidence of eye, mucous membrane, or skin irritation. Further tests, such as determinations of the concentrations of serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), and lactic dehydrogenase (LDH), may be considered by the responsible physician.
(3) An evaluation of the ability of the worker to use respirators.
(b) Periodic examinations shall be made available on an annual basis. These examinations shall include, but shall not be limited to:
(1) Interim medical and work histories.
(2) Physical examination as outlined in paragraph (a) (2) of this section. The responsible physician shall consider administering appropriate organ function tests.
(c) Proper medical management shall be provided for employees overexposed to epichlorohydrin. When there is known or suspected overexposure to epichlorohydrin, immediate first-aid measures shall be followed by prompt medical evaluation and followup assistance. First aid shall include removal of the employee from the area of excessive epichlorohydrin exposure, restoration of, or assistance in, breathing by trained personnel, and treatment of chemical burns.

# (d)
The responsible physician shall advise the worker that available information indicates that large doses of epichlorohydrin induce antifertility effects on rats; however, no effects on potency have been found. The relevance of this study to male or female workers has not yet been determined. It does, however, indicate that employers and workers should attempt to minimize exposures to epichlorohydrin whenever possible.
If the physician becomes aware of any adverse effects on the reproductive systems of workers exposed to epichlorohydrin, the information shall be forwarded to the Director, National Institute for Occupational Safety and Health, as promptly as possible. First Aid:
In case of skin contact, immediately remove all contaminated clothing, including footwear, wash skin with plenty of water for at least 15 minutes and call a physician. In case of eye contact, flush eyes with water for 15 minutes and call a physician.

# (b) Posting
Areas where epichlorohydrin is manufactured, stored, used, or handled shall be posted with a sign reading:

# EPICHLOROHYDRIN POISON! FLAMMABLE! SKIN CONTACT CAUSES DELAYED BURNS VAPOR IRRITATING TO EYES HARMFUL IF INHALED OR SWALLOWED
The sign shall be printed both in English and in the predominant language of non-English-reading workers, if any; the employer shall use these or other equally effective means to ensure that all employees know the hazards associated with epichlorohydrin and the locations of areas in which there is likely to be occupational exposure to epichlorohydrin. (1) Chemical safety goggles and face shields shall be provided by the employer and shall be worn during any operation in which epichlorohydrin may splash into the eyes. Suitable eye protective devices shall conform to 29 CFR 1910.133.
(2) Aprons, suits, boots, or face shields shall be worn when needed to prevent skin contact with liquid epichlorohydrin. The protective clothing for this purpose shall be made of impervious material, such as polyethylene, polypropylene, or polyvinyl chloride (PVC). Use of protective clothing made of neoprene, rubber, or leather is unsuitable.

# (b) Respiratory Protection
Engineering controls shall be used to maintain epichlorohydrin concentrations below the recommended environmental limits. Such control equipment shall be sparkproof. Compliance with the permissible exposure limit may not be achieved by the use of respirators except during the time necessary to install or test the required engineering controls, for nonroutine maintenance or repair activities in which brief exposures at concentrations in excess of the recommended limits may occur, and during emergencies when air concentrations of epichlorohydrin may exceed the recommended limits.
When a respirator is permitted by paragraph (b) of this section, it shall be selected and used pursuant to the following requirements:
(1) For the purpose of determining the type of respirator to be used, the employer shall measure, when possible, the concentration of airborne epichlorohydrin in the workplace initially and thereafter whenever process, worksite, or control changes occur which are likely to increase the epichlorohydrin concentrations; this requirement does not apply when only atmosphere-supplying, positive pressure respirators are used. The employer shall ensure that no worker is exposed to epichlorohydrin in excess of the recommended workplace environmental limits because of improper respirator selection, fit, use, or maintenance.
(2) A respiratory protection program meeting the requirements of 29 CFR 1910.134 shall be established and enforced by the employer.
The employer shall provide respirators in accordance with the provisions of both Table 1-1 and 30 CFR 11 and shall ensure that the employee uses the respirator provided.
(4) Respirators specified for use in higher concentrations of epichlorohydrin may be used in atmospheres of lower concentrations.
The employer shall ensure that respirators are adequately cleaned, and that employees are instructed in the use and the testing for leakage of respirators assigned to them.
Where an emergency which could result in employee injury from overexposure to epichlorohydrin may develop, the employer shall provide respiratory protection as listed in Table 1-1. (1) Gas mask (full facepiece) with chin-style or front-mounted organ ic vapor canister with impervious plastic cover for head and neck (2) Type C supplied-air respirator operated in the pressure-demand (positive pressure) or continuousflow mode with a full facepiece and impervious plastic cover for head and neck
Less than or equal to 1,000 ppm Type C supplied-air respirator with hood, helmet, or suit operated in the continuous-flow mode Greater than 1,000 ppm
(1) Self-contained breathing appa ratus with full facepiece operating either in the demand (negative pressure) mode or in the pressuredemand (positive pressure) mode worn under an impervious plastic suit with headpiece (2) Combination Type C suppliedair respirator with full facepiece operated in the pressure-demand (positive pressure) mode and an auxiliary self-contained air supply worn under an impervious plastic suit with headpiece (1) Self-contained breathing appa ratus in the pressure-demand (posi tive pressure) mode with full facepiece (2) Combination supplied-air res pirator with an auxiliary self-con tained air supply and full facepiece operated in the pressuredemand (positive pressure) mode Escape (no con centration limit)
(1) Gas mask (full facepiece) with chin-or front-mounted organic va por canister (2) Self-contained breathing appa ratus with full facepiece operated either in the demand (negative pressure) mode or in the pressuredemand (positive pressure) mode During cleanup operations, complete skin and respiratory protective equipment shall be used. After a cleanup operation, the employee shall be required to shower upon removing the protective equipment. If epichlorohydrin is spilled on shoes made of leather, canvas, rubber, or of any other permeable material, the shoes shall be rendered unusable and discarded.
If clothing is contaminated with epichlorohydrin, it shall be removed promptly and laundered thoroughly before reuse. (1) Entry into confined spaces, such as tanks, pits, tank cars, barges, process vessels, and tunnels, shall be controlled by a permit system. Permits shall be signed by an authorized employer representative certifying that preparation of the confined space, precautionary measures, and personal protective equipment are adequate, and that precautions have been taken to ensure that the prescribed procedures will be followed.
(2) Confined spaces which have contained epichlorohydrin shall be inspected and tested for oxygen deficiency, epichlorohydrin, and other contaminants, and, prior to entry by the employee, they shall be thoroughly ventilated, cleaned, and washed.
(3) Inadvertent entry of epichlorohydrin into the confined space while work is in progress shall be prevented by disconnecting and blocking of epichlorohydrin supply lines or by other appropriate means.
(4) Confined spaces shall be ventilated appropriately while work is in progress to keep the concentration of epichlorohydrin at or below the recommended environmental limits and to ensure an adequate supply of oxygen.
Individuals entering confined spaces where they may be exposed to epichlorohydrin shall wear either a combination Type C suppliedair respirator operated in the continuous-flow (positive pressure) mode or an auxiliary breathing air supply operated in the pressure-demand (positive pressure) mode equipped with a full facepiece, or a self-contained breathing apparatus operated in the pressure-demand (positive pressure) mode.
Each individual shall also wear a suitable harness with lifelines tended by another employee outside the space who shall also be equipped with the necessary protective equipment, including a self-contained breathing apparatus which operates in the pressure-demand (positive pressure) mode and has a full facepiece. Communication (visual, voice, signal line, telephone, radio, or other suitable means) shall be maintained by the standby person with the employees inside the enclosed spaces.
(g) For all work areas where epichlorohydrin is used, procedures as specified in this section, as well as any other procedures appropriate for a specific operation or process, shall be formulated in advance.
Employees shall be comprehensively instructed in the implementation of emergency procedures.
( Epichlorohydrin is a reactive molecule which may form covalent bonds under biologic conditions.  In reactions with alcohols, amines, thiols, and other nucleophilic biochemical constituents of the cell, the epoxide ring opens and forms a new, stable, covalent carbon-hetero atom bond as shown in the reaction In Figure XIII-1. The initial reaction product may undergo a second nucleophilic reaction to form stable, covalent cross-linking bonds between two molecules either by direct displacement of the chlorine atom or through the formation of an unstable, short-lived cyclic intermediate.  These cross-linking bonds may have a high degree of chemical stability, such as is typically found in epoxy resins.  The chemical characteristic of epichlorohydrin to react as a bifunctional alkylating agent is an intrinsic property of its molecular structure.
Biologic organisms contain many different chemical nucleophiles, such as alcohols, acids, amines, sulfhydryls, carbohydrates, lipids, proteins, ribonucleic acids, and deoxyribonucleic acids.  Epichlorohydrin has a greater tendency to react with more readily polarized groups, such as sulfhydryl groups, than with less readily polarized groups, such as hydroxyls.
The half-life of epichlorohydrin in water at a pH of 7 is 36.3 hours.  Although the half-life of epichlorohydrin in biologic tissues is not known, the known presence of large numbers of nucleophiles in tissue suggests that it is shorter than the half-life in water. Mammalian enzymes which catalyze the hydrolysis of epichlorohydrin, or otherwise degrade it, would further decrease the biologic half-life. Under hypothetical, constant, nonlethal exposure conditions, a steady-state concentration of epichlorohydrin would eventually be achieved in all tissues, resulting in a steady-state rate of alkylation of tissue constituents. For reviews of the pertinent literature, the reader is referred to Ross  and Loveless.  Extent of Exposure Epichlorohydrin is commercially synthesized from allyl chloride,  allyl alcohol,  dichlorhydrin-glycerine,  or propylene.
The total US production of epichlorohydrin was about 550 million pounds in 1975.
 Projected expansion plans, if accomplished, would increase total production to 715 million pounds by 1978.  In 1969, the total US production of crude epichlorohydrin was about 322 million pounds.  An estimated 58% of this was used in the manufacture of synthetic glycerine and 42% was processed to refined epichlorohydrin.  Refined epichlorohydrin is used in the manufacture 
A number of cases of dermal sensitization have been reported in workers in the epoxy resin-producing and resin-using industries.  Attempts to identify the causative agents have been only partially They felt that specific work practices were necessary since epichlorohydrin penetrates rubber and leather. They noted that there was a latent period of several minutes to several hours between contact with epichlorohydrin and its manifestations.
The authors drew attention to similar latent periods for burns caused by X-rays or by such alkylating agents as ethylene oxide.
The authors  recommended that studies of the peripheral vasculature be done as soon as possible after dermal contact with epichlorohydrin to distinguish between sequelae and preexisting vascular alterations. This recommendation was made because of the persistent erythema observed after every accident and the pronounced peripheral arteriosclerosis diagnosed in one patient. No indication of sensitization was reported in the two workers whose contact with epichlorohydrin was repeated. These cases demonstrated that skin exposure to liquid epichlorohydrin can cause severe chemical burns. When skin contact with epichlorohydrin was short, the severity of the burns was much less than when skin contact was prolonged. Therefore, it can be concluded that the intensity of the burns is dependent on the duration and extent of exposure, which control the extent of reaction with cellular constituents.
In 1966, Pet'ko et al  investigated the health of workers engaged in the production of epichlorohydrin from dichlorhydrin glycerine (DCG) in Russia. Environmental monitoring for both epichlorohydrin and DCG was done by an unspecified sampling method. In some instances, the epichlorohydrin concentration in air was reported to be 2-14 times greater than its maximum Although the authors considered the individual worker's length of service to be unrelated to the nature and frequency of the complaints, they did not report the nature of the complaints. They concluded that no deviations from the normal which could be interpreted in terms of occupational factors, other than two cases of occupational dermatitis, were identifiable. The dermatitis cases were not discussed. Pet'ko et al  recommended that further studies be done, and that annual medical examinations by an internist, a dermatologist, and a neuropathologist be given. The authors gave no explanation for including a neuropathologist, nor did they specify the clinical basis for recommending blood and urine examinations. With Fregert as the subject, the authors found that, following application for 2 days of patches containing epichlorohydrin diluted to 0.1, 0.5, and 1.0% with ethanol, no immediate effects on the skin were visible, but reactions developed after 8-11 days at all test sites.
Retesting with 0.1 and 0.01% epichlorohydrin induced a positive reaction after 2 days to 0.1% epichlorohydrin and resulted in erythema with 0.01% epichlorohydrin.
Propene oxide, 0.2% in ethanol, gave a positive reaction when it was applied to skin previously exposed to epichlorohydrin.
Negative reactions were obtained with 1-chloropropane (1%), l-chloro-2propanol (1%), and ethylene oxide (1%) after application of these compounds to areas where epichlorohydrin had been applied. They concluded that the epoxy group and the three carbon atoms in the chain, but not the chlorine, No details of these exposures were given.
In addition, the method by which the epichlorohydrin concentrations were measured or verified was not reported.
In the absence of such information, it is reasonable to assume that these observations are derived from accidental occupational exposures to epichlorohydrin. In the absence of further details on the extent of epichlorohydrin exposure and individual histories, no general conclusions can be drawn from these data.
In the majority of the 48 cases, the deviations from normal ranges were no longer detectable after a few months.
In five of the reported cases, however, one or more of the measured values remained outside the normal range from 7 to 13 years after exposure. Reexamination of one of these men about 4.5 months later gave values for the various measurements that were within the normal ranges.
From the available data, it is not possible to attribute these persistent changes solely to epichlorohydrin exposure. The most frequently observed deviations from the normal ranges were a decrease in the percentage of polymorphonuclear leukocytes and an increase in the percentage of monocytes in the total leukocytes count of the blood; even these changes were not consistent in any employee. The data suggest that a detailed study of the medical histories of these individuals and their possible exposure to other chemicals is necessary before the hazards of permanent injury from epichlorohydrin exposure can be evaluated. These all illnesses during epichlorohydrin exposure were respiratory and only 24 (27%) were respiratory during nonexposure to epichlorohydrin. The consultants concluded that illness during employment in an epichlorohydrinexposure area is more likely to be respiratory than one during employment elsewhere.
Examination of the ECG revealed that 5.0% of the employees in the minimal-exposure group and 2.7% in the moderate-exposure group had abnormal records.
The consultants concluded that epichlorohydrin exposure had not influenced the ECG records.
Study of pulmonary roentgenograms indicated that, in both the moderate-and minimal-exposure groups, 1.8% contained abnormal findings, such as emphysematous blebs, mild pneumonic infiltration, pneumonia, mild chronic pulmonary fibrosis, minor emphysema, and infiltrative lesions. The consultants noted that, in addition to the same frequency of abnormal X-radiographs in both exposure groups, a rate of 1.8% did not appear to be greater than that which might be expected in similar unexposed workers.
The urinalysis showed no clear difference between the two exposure groups or any group tendency toward abnormality. Hematocrit index, lymphocyte count, SGOT and SGPT activities, and creatinine and BUN values were within the normal range. White blood cell counts were above the normal limit during the 4th, 8th, and 12th years of employment for the moderate-exposure group.
The mean group values for monocyte cell count were within normal limits except for the employees with more than 6 years of moderate exposure, in whom values fluctuated fairly widely around the laboratory normal. The difference between the average values for the two exposure groups was statistically significant (t value was 4.35 at a P value of less than 0.05) at the 3rd year. Eosinophil cell count was slightly elevated for the moderate-exposure group during the 2nd and 5th years of epichlorohydrin exposure. Lactate dehydrogenase activity was elevated in both groups. Examination of pulmonary function data indicated that the mean values for both groups did not differ from their normal values. The albumin-to-globulin ratio was normal for both groups, but, at the 4th year of exposure, the ratio for the moderate-exposure group was significantly lower (t value 3.88, with a P value of less than 0.05) than that of the minimal-exposure group. Based on all these findings, the consultants concluded that there were no toxic effects on the blood, liver, or kidneys related to the epichlorohydrin exposures.
This study, although helpful, is inadequate to fully estimate the health hazards associated with epichlorohydrin exposure for several reasons.
The data base comprises a group of employees occupationally exposed to epichlorohydrin for periods of 6 months-16 years, but no consideration was given to those who dropped out because of illness, retirement, or death. There is no way to evaluate from this study the importance of the group lost from the observation. A major deficiency of this study is the lack of a control group. In the absence of such a group, the "normal" range of the clinical and the biochemical tests is dependent on laboratory values alone. Further, because of the lack of controls, the consultants compared the effects of the moderate-exposure group with those of the minimal-exposure group. The consultants stated that the measure of exposure was "a crude one" and that it was only an estimate by the company of whether a given individual's exposure was minimal or moderate. No quantitative data with regard to exposure were provided, and there is no indication of even what range of concentration was referred to by the classifications "moderate" and "minimal." Therefore, any absence of doserelated effects could be accounted for both by the absence of a clear distinction between the groups and by loss of an affected segment of population. From the biochemical data, it is possible to conclude that groups of individuals "exposed" to epichlorohydrin do not show variations from the measured norms held to be appropriate by the laboratory. Further, because of the deficiencies discussed in this paragraph, the significance of the finding on respiratory tract illness is dubious. If the number of tests in any year of employment was related to the number, of employees, the length of employment in the moderate-exposure group was much shorter than in the minimal-exposure group, ie, less than half the workers were still employed during the 1st year and available for tests.
In Lung congestion, edema, consolidation, and inflamed areas with signs of abscess formation were also observed. Although epichlorohydrin is the most plausible causative agent, the absence of controls exposed to the propanol vehicle alone makes it difficult to attribute these changes solely to epichlorohydrin.
The rats exposed to epichlorohydrin at 56 ppm for 18 periods (approximately 864 mg/kg total amount inhaled) showed respiratory distress, nasal discharge, and weight loss.
 Urinary protein excretion, hemoglobin concentrations in blood, and differential cell counts were normal.
Microscopic examination showed only an abscess in one lung, which the author did not attribute to epichlorohydrin exposure.
Rats exposed to epichlorohydrin vapor at 27 ppm for 18 days (approximately 417 mg/kg total amount inhaled) showed mild nasal irritation.
 The lung of one rat contained hemorrhagic and consolidated areas. Rats exposed to epichlorohydrin at 17 ppm for 19 exposure periods showed no apparent effects at necropsy or on histopathologic examination. This exposure most likely resulted in an estimated inhaled amount of about 277 mg/kg. Two of eight rats developed pulmonary infections when exposed to epichlorohydrin at 9 ppm for 18 exposures (approximately 139 mg/kg, total amount inhaled); no effects were observed in the other six animals.

# Gage
 also exposed two groups of two rabbits each to epichlorohydrin vapor. The periods of exposure were not mentioned, but probably, like the rats, the rabbits were exposed 6 hours/day, 5 days/week.
The first group was exposed for 20 daily periods at 35 ppm (approximately 439 mg/kg total amount inhaled). The second group was exposed for two periods at 16 ppm (approximately 20 mg/kg total amount inhaled). The latter exposure was reduced to 9 ppm and was continued for 20 more days (approximately 113 mg/kg total amount inhaled). Thus, the second group of rabbits is estimated to have inhaled a total amount of 133 mg/kg.
Inhalation of epichlorohydrin at 35 or 16 ppm produced nasal irritation.
At 9 ppm, no adverse effects were observed. Post-mortem examination did not reveal any abnormalities. Subsequent to these observations, Gage  recommended that the epichlorohydrin concentration in the occupational environment where employees are working continually without respiratory protection should not exceed 5 ppm. However, It is noted that Gage did not attempt to investigate any long-term effects of epichlorohydrin inhalation since the longest exposure lasted only 19 days. The recommendation of 5 ppm was therefore based only on effects resulting from short-term exposure.
In 1961, Kremneva and Tolgskaya  reported the effects of epichlorohydrin on mice, rats, and rabbits. Routes of administration were stomach intubation, subcutaneous injection, inhalation, and skin and eye application. Three groups of 10 mice and 5 rats each were administered aqueous solutions of epichlorohydrin by stomach tube in doses of 500, 325, and 250 mg/kg. All animals given doses of 500 or 325 mg/kg died within the first 2 days. In both rats and mice, the same type of intoxication pattern was evident: low mobility, slow and labored breathing, hyperemia of the skin, subcutaneous bleeding, ataxia, periodic body tremor, and distention of the abdomen. Microscopic examination of tissues of the dead animals revealed plethora of the internal organs, hemorrhage and edema of the lungs and pulmonary tissue, vacuolization of the liver cells with what was described as fatty degeneration, and degenerative processes in the epithelium of the convoluted tubules accompanied by some necrosis in the kidneys.
Foci of necrosis in the stomach and intestinal mucosa also were observed. At the 250-mg/kg dose, no visible signs of intoxication were evident during the 14-day observation period.
A total of 50 mice were injected with epichlorohydrin at doses of 500, 375, 250, and 125 mg/kg.  The results of the injections were not described except that, at doses of 500 and 375 mg/kg, all of the mice died, and, at 250 mg/kg, 7 of 10 mice died. Epichlorohydrin at a dose of 125 mg/kg was tolerated without visible alteration in the behavior of the mice.   To assess the irritant effects on eyes, 0.1 ml of epichlorohydrin solution in cottonseed oil was instilled into the right eyes of the rabbits; the left eyes served as the untreated controls.
 The eyes were examined every 30 minutes for 3 hours. Corneal damage was present in 80% of the animals and a lesser degree of irritation occurred in the rest of the animals. Epichlorohydrin was found to be a strong ophthalmic irritant.
There was no evidence of sensitization to epichlorohydrin, as determined by the maximization test in 5 Hartley-strain guinea pigs.
Groups of 12 male Sprague-Dawley rats were injected ip daily for 30 consecutive days with 0.00955 or 0.01910 ml/kg of epichlorohydrin or 0.01910 ml/kg of cottonseed oil. At the end of 30 days, hemoglobin values were increased significantly at the low dose but decreased significantly at the higher dose (P values less than or equal to 0.05). The concentration of neutrophilic metamyelocytes increased significantly (P value less than or equal to 0.05) in the high-dose group but remained equal to that of controls for the rats administered epichlorohydrin at the lower dose.
Lymphocytes showed an insignificant dose-related decrease in frequency. A slight, insignificant dose-related increase in clotting time was also observed. Hepatic function, as measured by the BSP test, was not impaired.
The heart-to-body weight ratio increased in a dose-related way but the increases were not statistically significant. The ratio of the weight of the kidney to body weight increased significantly with both doses (P value less than or equal to 0.05). The ratio of brain-to-body weight of the rats was higher in the epichlorohydrin-treated rats than in the controls.
Microscopic examination did not reveal changes in any organs except in the lungs. Lesions in the lungs were evident in all groups, but the incidence and severity were "somewhat greater" in the treated animals than in the controls. It is noteworthy that the authors did not detect any kidney damage in the microscopic examination. All animals treated with epichlorohydrin had lower hematocrit and erythrocyte counts than the control rats, but this was significant (P value less than or equal to 0.05) only for the hematocrit value of the middle-dose group. An increase in the concentration of platelets in the blood also was observed in the epichlorohydrin-treated animals. Total leukocyte counts were lower in the low-dose group and higher in the highest-dose group than in the control group. These differences were not significant (P value less than or equal to 0.05). Leukocyte counts for the middle-dose and control groups were the same. A dose-related increase in the average percentage of segmented neutrophils was observed but was significant (P value less than or equal to 0.01) only for the high-dose group. The percentage of eosinophils increased in all experimental groups, the increases in the low-and the high-dose groups being significant (P value less than or equal to 0.05).
Significant reductions in the percentage of lymphocyte in the total leukocyte count were observed in the animals treated with the two highest doses (P values less than or equal to 0.05 and 0.01, respectively). The ratio of the weight of the brain to that of the body was significantly lower (P value less than or equal to 0.01) in the animals treated with epichlorohydrin at the highest dose than in the control animals; this is in contrast to the effect obtained in animals receiving 30 daily doses of epichlorohydrin.
The change in the brain-to-body weight ratio suggests abnormal changes in the CNS. The organ weight-to-body weight ratios for heart, kidneys, and liver were significantly (P values less than or equal to 0.01, 0.01, and 0.05) higher for the animals treated with the highest dose than for the controls. The ratio of spleen-to-body weight was not significantly different from that found in the controls.
The results indicate that repeated doses induce a cumulative effect on basic cellular growth with a subsequent perturbation of the normal rates of growth of these internal organs.
The effect of epichlorohydrin on pentobarbital-induced sleeping time was studied in mice.
 Male ICR-strain mice in groups of 10 were administered 1/10, 1/5, or 1/2 of the acute ip LD50 dose (0.14 ml/kg) of epichlorohydrin. Control mice were administered ip saline injections.
Similar groups of mice were exposed to epichlorohydrin vapor at 1/10, 1/5, or 1/2 of the LT50 dose (71.89 mg/liter, 9.13 minutes). Control mice were placed in an inhalation chamber and were exposed to uncontaminated air.
Twenty-four hours after exposure to epichlorohydrin by either route, 50 mg/kg of sodium pentobarbital was administered ip. A dose-related increase in sleeping time was observed in all the epichlorohydrin-treated animals;
however, the only significant increases (P value less than or equal to 0.01) were in the groups receiving the highest ip dose or the highest inhalation exposure. Based on these extensive studies, it can be concluded that epichlorohydrin is severely irritating to the skin and the eyes, and perhaps to the lungs. Further, it also affects some metabolic processes of the liver. In most cases, the severity of its effects appears to be dose dependent.
In 1972, Lawrence and Autian   Severe lesions of the neurons in the medulla oblongata, Ammon's horn, and cerebellum were also present.
Animals inhaling epichlorohydrin at 0.5 ppm showed an increase in leukocytes with altered fluorescence, a decrease in the nucleic acid content of the blood, but no significant effects on the amount of urinary coproporphyrin.
 The concentration of leukocytes with altered fluorescence increased significantly (95% probability of not being a variation by chance), but the effect was less marked than on the animals treated at the highest dose. Animals in the third group, inhaling epichlorohydrin at 0.05 ppm, did not show similar effects. There were no morphologic differences between the control animals and those in the last two groups.
Based on the results of this continuous inhalation study, Fomin  recommended that the mean diurnal maximum permissible concentration of epichlorohydrin in the atmosphere not exceed 0.2 mg/cu m (approximately 0.05 ppm). The exposure in this study was continuous and the effect of intermittent recovery periods was not evaluated.
In 1969, Golubev  recorded changes in the diameters of the pupils of the eyes of rabbits. Groups of six rabbits were used to ascertain the irritating effects of eight different chemicals, including epichlorohydrin.
The rabbits' eyes were illuminated with a uniform reflected light, and the diameters of the pupils were measured with an instrument referred to as a tangential pupilometer. A 0.25 M solution of epichlorohydrin was instilled into the conjunctival sacs and the pupil diameters were measured 1, 3, 5, 10, 15, 20, 25, and 30 minutes later. In the control rabbits, the pupil diameters were measured both before instillation and at similar time intervals after instillation of 0.05 ml of saline solution into the conjunctival sacs.
Epichlorohydrin caused constriction ranging from 1 to 16% during the first 20 minutes, the initial diameter being considered 100%. The author noted that this effect was elicited at an epichlorohydrin concentration that caused no visible changes in the conjunctivae or cornea.
Thus, epichlorohydrin at 0.25 M (2.3%) has a measurable effect on the eyes.
In 1968, Pallade et al  subcutaneously injected 67 white rats with a single dose of epichlorohydrin at 125 mg/kg to investigate epichlorohydrin-induced kidney damage.
Prior to injection, the urine of each animal was examined for protein, potassium, and sodium; thus, each animal served as its own control. The animals were kept in metabolism cages; their urines were examined 1, 2, 3, and 8 days after epichlorohydrin administration.
Oliguria or anuria was exhibited by 53 (79%) animals and polyuria by 4 (6%). The remaining 10 (15%) produced urine at normal rates.
Of the 53 rats that produced little or no urine during the period immediately after the administration of epichlorohydrin, 7 (13.2%) entered a stage of polyuria within 2-3 days after the administration of the dose.
The mortality rate was 13.4%, death occurring only among the oliguric and anuric animals. Pallade et al  noted that proteinuria and the parallel oliguric and anuric conditions indicated the occurrence of renal damage. If tissue repair and regeneration had occurred, the animals survived. They concluded that the signs of renal disorders confirmed that epichlorohydrin is nephrotoxic to rats. Therefore, medical examinations oriented to the detection of renal disorders were recommended for workers exposed to epichlorohydrin. Information on how epichlorohydrin vapor was generated and information on the size of the chamber were not provided. Neither was it indicated whether the chamber was operated in the static or the dynamic mode. The total amounts of epichlorohydrin inhaled during each of the 4-hour exposure periods are estimated to have been approximately 51, 2.9, and 1.0 mg/kg, respectively.
The same effects seen in the previous experiment  were observed.
In addition, the weights of the liver and kidneys were increased, whereas those of the lungs and the spleen were decreased.
Removal of BSP from blood was decreased on the day of exposure, but not reliably on the day after the exposure. The production of urine was increased by all three levels of exposure, with concomitant decreases in the specific gravity of the urine. The daily output of chlorides in the urine on the day after exposure was usually increased by a larger factor than the production of urine. The daily excretion of protein in the urine was also increased, but less than that of chlorides. No additional studies of pulmonary and splenic function were reported. Reductions in both oxygen consumption and body temperature also were observed.
A significant (P value not given) stimulating influence on the mobility of spermatozoa also Renal cytochrome oxidase activity was determined in 14 rats and in 10 controls 24 hours after they had been injected with epichlorohydrin.  Statistically significant (P value less than or equal to 0.01) inhibitions were observed in treated animals. Renal succinic dehydrogenase activity, determined 24 hours after epichlorohydrin administration, was similar for 10 experimental and 6 control animals. Examination of 40 treated and 30 control rats showed reductions in renal carbonic anhydrase activity of 6-11% 24 hours after the administration of epichlorohydrin. This reduction was not statistically significant. Glutamic-pyruvic transaminase (GPT) (E.C. 2.6.1.2) activity was measured 2.5 and 24 hours after administration in both renal tissue and serum. There were 30 animals in the group examined at 2.5 hours after epichlorohydrin administration and 40 in the group examined 24 hours postdose. At 2.5 hours, no change was observed in the kidneys, but a statistically significant (P value less than or equal to 0.01) increase in SGPT activity was observed at both the 2.5-hour and the 24-hour intervals. A significant reduction (P value less than or equal to 0.01) was observed at 24 hours; there were 0.230 units of activity in the controls in contrast to 0.100 units in the experimental group. The average SGPT activity in the experimental group ranged from 0.051  0.022 units at 2.5 hours to 0.058  0.018 units at 24 hours, in contrast to the control group average of 0.034  0.010 units. Glutamic-oxaloacetic transaminase (GOT; E.C. 2.6.1.1) activities in the kidney were similar for the controls and the intoxicated animals at 2.5 hours, but significantly (P values less than or equal to 0.01) different at 24 hours in the experimental rats (0.261  0.046 units) versus 0.302  0.040 units in the controls. SGOT activity was significantly increased in the experimental rats, 0.045  0.009 units at 2.5 hours (P value less than or equal to 0.02) and 0.046  0.010 units at 24 hours, (P value less than or equal to 0.01) in contrast to 0.040  0.008 units observed in the controls. Alkaline phosphatase activity was assayed in 30 experimental animals and in 30 controls. The animals given epichlorohydrin showed a significant reduction (P value less than or equal to 0.01) in the mean kidney phosphatase activities (0.029  0.008 units) at 2.5 hours but had a mean alkaline phosphatase activity comparable with that in the controls (0.033  0.014 units) at 24 hours.
However, serum alkaline phosphatase activity decreased progressively at 11-day period had no effect on body weight. Inhalation exposure at a concentration of 0.6 mg/liter of epichlorohydrin for 4 hours/day for eight times during 11 days decreased body weight by about 9%. Combination of these two exposures, that to heat following immediately after that to epichlorohydrin, had the same effect on body weight as exposure to the chemical alone. This finding agrees with that relating to the LC50. In conclusion, the amount of heat stress had no effect on these two responses of rodents to epichlorohydrin. Despite these two negative findings, there were a few instances in which addition of heat stress seemed to modify toxic actions by the chemical stressor. Thus, rats exposed to both heat and epichlorohydrin were reported to have had somewhat less marked alterations of the structure of the liver and the thyroid follicles, but more pronounced ones of the adrenal medulla, than those exposed to epichlorohydrin alone. Five rats showed moderate accumulations, resembling abscesses in some instances, of leukocytes around blood vessels in the interstitial tissue of the thyroid. A dose of 150 mg/kg of epichlorohydrin was administered to 10 male mice by ip injection. Each male was then caged with three undosed virgin female mice for 1 week. The females were replaced each week for 8 weeks and then killed and examined for pregnancy. The numbers of total live implants, early fetal deaths, and late fetal deaths were recorded. Since, in general, late fetal deaths were exceedingly rare, total implants and early fetal deaths were the only features of pregnancy analyzed. The authors did not report the observation of any effects of epichlorohydrin on early fetal deaths or other reproductive characteristics, including male fertility.
Therefore, it can be concluded that epichlorohydrin at 150 mg/kg given to male mice in a single ip injection does not increase the ratio of early fetal deaths to the total number of implantations occurring in the uterus of the female mice to which they are mated.
A summary of the results of the animal studies, other than for carcinogenicity and mutagenicity, is presented in Table III In the mice injected with epichlorohydrin, there was a sl^in papilloma after 11.5 months, a hepatoma in another mouse after 13 months, and 2 lung adenomas in 1 mouse after 24 months. The control animals had occasional hepatomas and lung adenomas, but no skin papillomas. The survival of the epichlorohydrin-treated animals was poor. During the 1st year, 12 mice died; after the 2nd year, only a few survived. Falk noted that, except for the single skin papilloma, the tumors were generally of the same type and frequency of occurrence as in the control groups. Thus, the experiment was inconclusive. initially and whenever necessary during the experiment. A dose of 2.0 mg of epichlorohydrin in 0.1 ml of acetone was applied three times/week to the interscapular region. The test lasted for 580 days (83 weeks). Skin lesions were diagnosed as papillomas when they reached 1 cu mm in size and persisted for 30 days or more. No papillomas or carcinomas occurred in the animals to which epichlorohydrin, acetone, or nothing was applied.
A group of female ICR/Ha mice had 2.0 mg of epichlorohydrin in 0.1 ml of acetone applied to the skin followed 2 weeks later by three applications each week, and throughout the study (total duration, 385 days), of 2.5 jug of phorbol myristate acetate (PMA), a promoter, in 0.1 ml of acetone.
In the group of 50 mice to which epichlorohydrin was applied, nine mice developed papillomas and one a carcinoma. Control animals to which solvent (30) alone or no chemical (100) was applied produced no tumors. Of the mice to which PMA alone (30) was applied, three developed papillomas.
For an assay by subcutaneous injection, 50 mice were injected weekly in the left flank with 1.0 mg of epichlorohydrin in 0.05 ml of tricaprylin.
 This test also lasted for 580 days.
Of the animals given epichlorohydrin, six developed sarcomas and one an adenocarcinoma (P value less than or equal to 0.05). In comparison, 1 mouse of 50 injected with tricaprylin alone developed sarcoma, and none of the control animals developed any tumors. The significance of subcutaneous sarcomas which occur at the injection site has been discussed by Grasso and Golberg.  In an ip assay, 30 mice received weekly injections into the lower abdomen of 1.0 mg of epichlorohydrin in 0.05 ml of tricaprylin. The experiment was terminated after 450 days. None of the mice developed local sarcomas, but 11 had papillary lung tumors. Of mice given tricaprylin alone, 10 had papillary tumors of the lungs and 1 developed a local sarcoma.
The results of these studies raise concern about an additional risk of carcinogenesis for the segment of human population continuously exposed to epichlorohydrin throughout the working lifetime. Available experimental evidence  indicates that the risk of induction of cancer in animals and in humans can be reduced by reducing the maximum allowed cumulative dose to which they are exposed. Based on these reports, further tests involving long-term inhalation exposures of animals to epichlorohydrin must be done to determine the degree of occupational risk following chronic inhalation of epichlorohydrin.
A tabular summary of results of the carcinogenic studies is presented in  Recently, workers exposed to epichlorohydrin were monitored for the presence of mutagens in their urine (DJ Kilian, written communication,   The most plausible molecular basis of the epichlorohydrin-induced mutations in all of these organisms is the covalent bonding of epichlorohydrin to the cellular genetic material, DNA. In view of the virtual irreversibility of these reactions, the degree of genetic damage may be expected to increase with exposure time in these lower organisms as well as in higher forms.
Reports of experimental attempts to induce the formation of terata by exposing pregnant female animals to epichlorohydrin have not been found.      Sampling was conducted with charcoal tubes using a calibrated, battery-operated pump. Quintuplicate samples were taken for each job classification at a rate of 2 liters/minute for 7 hours. Epichlorohydrin and chlorinated hydrocarbons were extracted with 30 ml of carbon disulfide.
Epichlorohydrin recovery from the charcoal, after sampling, was found to be 65%. Analysis was performed with a hydrogen flame chromatograph equipped with a 12 feet x 1/8 inch column packed with 15% Oronite NiW on gas chrom CLA (60-80 mesh). In 1973, in the epoxy resin unit, one air sample in the breathing zone of each of four employees (three operators and one helper)
showed the average epichlorohydrin concentration to be 0.03 ppm.
In the same year, 78 grab samples indicated that epichlorohydrin concentrations ranged from 13 ppm to less than 0.60 ppm, with an average of 3.17 ppm. It should be noted that the "average" was a numerical average between the individual samples,-not the TWA concentrations. The results of air monitoring done in 1974 are presented in Table IV-  From reference 2
Pet'ko et al  reported the results of environmental monitoring done in epichlorohydrin and dichlorhydrin-glycerine production units in Russia. The sampling technique employed was not specified. Concentrations  Data on collection efficiency were not given. However, sampling with silica gel in high humidity may result in considerable sample loss from the displacement of the organic vapors by water vapor. Whitman and Johnston  reported that this problem could be overcome with a molecular sieve prefilter. They used a 5-Angstrom molecular sieve to remove water vapor from gas streams without interfering with the passage of aromatic hydrocarbons. White et al  have described the design of activated charcoal tubes suitable for sampling, and such tubes are commercially available. Adsorption on activated charcoal is the preferred sampling method for epichlorohydrin alone for several reasons: epichlorohydrin is not displaced by water vapor as it is from silica gel; it is a simpler, more convenient procedure than the use of plastic bags or of a bubbler; it uses a small, portable sampling device, and the difficulties associated with handling liquids are eliminated. Disadvantages are that the amount of sample that can be collected is limited by the number of milligrams that the charcoal tube will hold before overloading, and that the more volatile compounds can migrate to the backup section during storage before analysis.
Various methods used for analyzing the collected samples have included colorimetry,  infrared analysis,  and gas chromatography.  Colorimetric analysis suitable for analyzing epichlorohydrin in an aqueous solution has been used.
 The colorimetric method  is based on the oxidation of epichlorohydrin in aqueous solution by periodic acid. Epichlorohydrin in water is hydrolyzed to a glycol which is then oxidized to formaldehyde. Epichlorohydrin solutions of known concentrations are prepared to obtain the standard curve.
The formaldehyde further reacts with sodium arsenite and acetylacetone reagent to form a yellow complex. The acetylacetone reagent solution is prepared by mixing ammonium acetate, acetylacetone, and glacial acetic acid in water. Maximum optical density of the yellow complex occurs at about 412 nm. This method was capable of determining as little as 20jug of epichlorohydrin. Data on the efficiency of the analytical technique were not given.
 Formaldehyde, or any substance that may yield formaldehyde under the test conditions, will interfere. Compounds that contain or would form vicinal terminal hydroxy groups, such as ethylene glycol and ethylene oxide, will also interfere.
A colorimetric method  suitable for analyzing epichlorohydrin collected in sulfuric acid also has been used.
Air containing epichlorohydrin was drawn through two bubblers containing 3 ml of 20% sulfuric acid and 4 ml of 10% sulfuric acid, respectively. The content of the first bubbler was diluted 1:1 with water. A 3-ml sample was then oxidized with 0.5 ml of 3% potassium iodate solution and allowed to stand for 30 minutes, during which time a yellow color developed. A 10% sodium sulfite solution was added and the mixture was shaken until the color disappeared.
One milliliter of Schiff's reagent was then added and the intensity of the resulting color (magenta) was measured 1 hour later. The initial reactions occurring were similar to those in the previously discussed colorimetric method.
 Epichlorohydrin is hydrolyzed by sulfuric acid and the resulting glycol is oxidized to formaldehyde by the iodate. The formaldehyde then reacts with Schiff's reagent to form a magenta complex.
Sodium sulfite is added to reduce the unreacted iodate.
It was found that this method was capable of analyzing 0.01-0.1 mg epichlorohydrin in a 6-ml solution. Data on sensitivity, specificity, and interferences were not reported. However, the same compounds that would interfere with the previously discussed colorimetric technique,  such as ethylene oxide and ethylene glycol, would also interfere with this method. In addition, many aldehydes would interfere.
The formaldehyde can also react with phenylhydrazlne hydrochloride to form phenylhydrazone.
 The phenylhydrazone of formaldehyde reacts with potassium ferricyanide to form a colored complex. The maximum optical density of this complex occurs at about 500 nm. Epichlorohydrin concentrations ranging from 0.45 to 14 mg/cu m in air were determined by this method. Precision tests indicated the maximum error between the two determinations to be only 0.3%.
The infrared absorption spectrum of epichlorohydrin showed the typical terminal epoxide absorption bands.  The minimum amount of epichlorohydrin that was detected by infrared absorption was 0.3% (v/v in aqueous solution).  However, a practical and detailed technique using infrared analysis for a quantitative determination of epichlorohydrin has not been developed.
In recent years, gas chromatography has become the method of choice of most investigators for separation and the analysis of organic materials.
 It offers excellent specificity and sensitivity and is suitable for analyzing samples of airborne contaminants collected on charcoal.
Interferences are few, and most of those which do occur can be eliminated by altering the instrumental conditions. Muganlinsky et al  developed a linear temperature program to analyze epichlorohydrin in the presence of chlorinated hydrocarbons which may be present as impurities.
The recommended methods for sampling and analyzing epichlorohydrin are collection by charcoal tube and analysis by gas chromatography.
Sampling involves the collection of personal samples on charcoal tubes, and analysis involves desorption with carbon disulfide and measurement with a gas chromatograph equipped with a suitable detector. [ Such a notation refers to the potential contribution to overall exposure by the cutaneous route, including mucous membranes and eyes, either by airborne or, more particularly, by direct skin contact with liquid epichlorohydrin. This designation is intended to indicate the need for appropriate measures for the prevention of cutaneous absorption so that the TLV is not invalidated.
The present federal standard (29 CFR 1910.1000) for occupational exposure to epichlorohydrin is 5 ppm as an 8-hour TWA limit. This standard was based on the ACGIH TLV.
In Russia and in France, the maximum allowable concentration (MAC) in the industrial environment is 1 mg/cu m (0.26 ppm).  In the Rumanian Socialist Republic, 10 mg/cu m (approximately 2.6 ppm) of epichlorohydrin is the maximum concentration allowed in the occupational environment.  In the Federal Republic of Germany, the permissible environmental exposure limit is 18 mg/cu m (approximately 3.6 ppm), and 5 mg/cu m (approximately 1 ppm) in the German Democratic Republic.  The bases for these standards are not given. Air and water quality standards have not been found, although one recommendation of such a value (0.2 mg/cu m) has been presented.
Basis for the Recommended Standard
The induction of severe necrotic lesions occurring after dermal contact with epichlorohydrin has been reported.  Lung edema and kidney lesions were reported in humans exposed to epichlorohydrin at concentrations greater than 100 ppm for very short periods.  Changes in the voltage of the peaks of the alpha rhythm of the EEG measurements of volunteers exposed to epichlorohydrin at 0.08 ppm for a few minutes were reported by Fomin.
 Since the significance of the changes observed in this component of the EEG measurements is not known, further research needs to be conducted in this area before any interpretations can be made. Acute exposure to epichlorohydrin at a high, but unknown, concentration  caused irritation of the eyes and throat, nausea, and dyspnea; bronchitis with bronchiolar constrictions and enlarged liver were suspected to have resulted from this single overexposure. These findings  suggest that a ceiling is required. Since acute effects have been observed on humans at 20 ppm, and the lowest concentration which induces effects during a short interval has not been identified, a ceiling concentration of 19 mg/cu m (5 ppm), based on professional judgment, is recommended to protect even the more sensitive fraction of the working population from these adverse effects.
The existing federal standard of 5 ppm is based on the 1968 TLV.
Further information on cumulative aspects of toxicity such as sterility, carcinogenesis, and mutagenesis have been reported in subsequent studies.
[ The minimal concentration which has been observed to induce effects on rats (about 5 ppm) is used to approximate the permissible exposure in the occupational environment by weighing additional risk factors. The chronic effects for which risk must be considered are carcinogenesis, mutagenesis, and antifertility, as well as liver, kidney, and lung damage.
Van Duuren et al  found that a single application of 2.0 mg of epichlorohydrin on mouse skin initiated the tumorigenic process in at least 9 of the 30 experimental mice when it was followed by triweekly The total risk to the health of employees occupationally exposed to epichlorohydrin is the result of the independent risks due to carcinogenesis, mutagenesis, sterility, and damage to kidneys, liver, respiratory tract, and to the skin. At present, evidence for the existence of the risks, other than to skin depends primarily on data from experimental animal models. Concern for employee health requires that the probability of the occurrence of chronic effects be minimized. NIOSH recommends, therefore, that worker exposure to epichlorohydrin be limited to a concentration of 2 mg/cu m (0.5 ppm) as a TWA concentration. This value has been chosen on the basis of professional judgment, rather than on quantitative data which clearly distinguish no-effect concentrations from those at which adverse effects have been shown to occur in human populations.
A TWA concentration of 2 mg/cu m of epichlorohydrin should protect the employee against injury to organs during the individual's working lifetime, according to existing information. However, additional research is needed to provide support for the recommended environmental limit or to indicate the need for a different limit. The environmental limit implicitly assumes that the absorbed epichlorohydrin molecules will be detoxified by biochemical mechanisms, thereby reducing the risk of induction of human disease resulting from the cumulative toxicity of epichlorohydrin.
It is recognized that many employees handle small amounts of epichlorohydrin or work in situations where, regardless of the amount used, there is only negligible contact with epichlorohydrin.
Under these conditions, it should not be necessary to comply with all of the provisions of the recommended standard, which has been prepared primarily to protect employee health under all circumstances. For these reasons, "occupational exposure to epichlorohydrin" is defined as exposure above one-half the TWA environmental limit, thereby delineating those work situations which do not require the expenditure of resources for environmental monitoring and associated recordkeeping. Because of nonrespiratory hazards such as the production of burns on the skin in the use of epichlorohydrin, NIOSH recommends that appropriate work practices and protective measures to limit such contact be required regardless of the concentration of airborne epichlorohydrin. Further, the observation of changes in the concentration of biochemical constituents  following human and animal exposure to epichlorohydrin suggest that the health of the exposed workers be monitored frequently. Thus, it is recommended that comprehensive medical examinations be offered to all employees subject to occupational exposure to epichlorohydrin and that the responsible physician consider the advisability of also administering any liver and kidney function tests.

# VI. WORK PRACTICES
Work practices must be designed to minimize or to prevent inhalation of epichlorohydrin and skin and eyes from coming into contact with epichlorohydrin. Good work practices are a primary means of controlling certain exposures and will often supplement other control measures.
Enclosure of materials, processes, and operations is completely effective as a control only when the integrity of the system is maintained.
Such systems should be inspected frequently for leaks and any leaks found should be promptly repaired. Special attention should be given to the condition of seals and joints, access ports, and other such places.  Similarly, points of wear should be inspected regularly for damage. For this reason, clothing contaminated with epichlorohydrin must be removed immediately and thoroughly laundered before reuse. Shoes on which epichlorohydrin is spilled are to be rendered unusable and discarded. The protective clothing must be made of material not permeable to epichlorohydrin. Penetration through three types of rubber has been measured  and found to be 9-11 minutes for nitrile rubber, 20-22 minutes for neoprene rubber, and 38-43 minutes for natural rubber.
Since the penetration time is dependent on both the type of the rubber and the thickness, it is noteworthy that in this test  the thickness for each type of rubber was: 0.015 inches for nitrile rubber, 0.02 inches for neoprene rubber, and 0.030 inches for natural rubber.

# Mutagenic Effect
This effect must be systematically investigated in greater depth with respect to dose, time, and route in both lower organisms and mammals.
Animal tests using various doses, schedules, and routes of administration should be performed to see whether epichlorohydrin is a mutagen in mammals.
Specific locus tests or heritable translocations should be considered.
Animals should also be tested to see whether epichlorohydrin has any cytogenic effects.

# Kidney Function in Workers Exposed to Epichlorohydrin
The impairment of kidney function as a result of epichlorohydrin exposure has been found in animals. As yet, there is no evidence that such injury also occurs in workers exposed to epichlorohydrin. Since a segment of a working population which is exposed primarily to epichlorohydrin can be identified, kidney function tests should be given periodically to determine whether any changes in kidney function are occurring as a result of occupational exposure to epichlorohydrin.

# Skin Sensitization
Although epichlorohydrin is commonly stated to be a sensitizer of the skin, the data that have been found in this regard are far from complete or persuasive.  Additional information on the degree and character of sensitization of the skin of humans is highly desirable. Some measure of variability in the skin response would be most useful.

# Electroencephalographic (EEG) Studies
The index of effect by epichlorohydrin on humans that seems to be the most sensitive on the basis of the available information is a change in the voltage of the alpha rhythm of the EEG.
 More information on the doseresponse relationship for this effect and on its correlation with more usual alterations of function would be of great value. Collect enough samples to permit calculation of a TWA exposure for every operation or location in which there is exposure to epichlorohydrin.

# (a) Equipment
The sampling train consists of a charcoal tube and a vacuum pump.
(1) Charcoal tubes: Glass tubes, with both ends flamesealed, 7-cm long with a 6-mm OD and a 4-mm ID, containing two sections of 20/40 mesh activated charcoal separated by a 2-mm portion of polyurethane foam. The primary section contains 100 mg of charcoal, the backup section, 50 mg. A 3-mm portion of polyurethane foam is placed between the outlet end of the tube and the backup section. A plug of glass wool is placed in front of the primary section. Tubes with the above specifications are commercially available.
(  (2) Break the tips of a charcoal tube to produce openings of at least 2 mm in diameter.
Repeat the procedure in (7) above at least three times, average the results and calculate the flowrate by dividing the volume between the preselected marks by the time required for the soapbubble to traverse the distance. If, for the pump being calibrated, the volume of air sampled is calculated as the product of the number of strokes times a stroke factor (given in units of volume/stroke), the stroke factor is the quotient of the volume between the two preselected marks divided by the number of strokes.

# Determination of Desorption Efficiency
The desorption efficiency of a particular compound can vary from one laboratory to another and also from one batch of charcoal to another. Chemical substances should be listed according to their complete name derived from a recognized system of nomenclature.
Where possible, avoid using common names and general class names such as "aromatic amine,"
"safety solvent," or "aliphatic hydrocarbon" when the specific name is known.
The "%" may be the approximate percentage by weight or volume (indicate basis) which each hazardous ingredient of the mixture bears to the whole mixture. This may be indicated as a range or maximum amount, ie, "10-40% vol" or "10% max wt" to avoid disclosure of trade secrets.
Toxic hazard data shall be stated in terms of concentration, mode of exposure or test, and animal used, eg, "100 ppm LC50-rat," "25 mg/kg LD50-  The "Health Hazard Data" should be a combined estimate of the hazard of the total product. This can be expressed as a TWA concentration, as a permissible exposure, or by some other indication of an acceptable standard. Other data are acceptable, such as lowest LD50, if multiple components are involved.
Under "Routes of Exposure," comments in each category should reflect the potential hazard from absorption by the route in question. Comments should indicate the severity of the effect and the basis for the statement, if possible. The basis might be animal studies, analogy with similar products, or human experiences. Comments such as "yes" or "possible" are not helpful. Typical comments might be:
Skin Contact-causes delayed burns.
Eye Contact-some pain and transient irritation.
"Emergency and First Aid Procedures" should be written in lay language and should primarily represent first-aid treatment that could be provided by paramedical personnel or individuals trained in first aid.
Information in the "Notes to Physician" section should include any special medical information which would be of assistance to an attending physician including required or recommended preplacement and periodic medical examinations, diagnostic procedures, and medical management of overexposed employees. Respirators shall be specified as to type and NIOSH or US Bureau of Mines approval class, ie, "Supplied air," "Organic vapor canister," etc.
Protective equipment must be specified as to type and materials of construction.

# HEALTH, ED UC A TIO N, AND W ELFARE

# PUBLIC HEALTH SERVICE C E N T E R F O R D I S E A S E C O N T R O L N A T I O N A L I N S T I T U T E F O R O C C U P A T I O N A L S A F E T Y A N D H E A L T H R O B E R T A. T A F T L A B O R
and analytical procedure, was 7.21 and 5.33%, respectively. Under these conditions, the desorption efficiency was estimated to be 82.7%.

# Apparatus (a)
Gas chromatograph equipped with a flame ionization detector. (1) 20 ml/minute helium flowrate.
(3) 200 C injector temperature.
(3) 230 C manifold temperature (detector).
(4) 135 C isothermal oven or column temperature.

# Analysis of Samples

# MATERIAL SAFETY DATA SHEET

# PRODUCT IDENTIFICATION M A N U F A C T U R E R 'S N A M E R E G U L A R T E L E P H O N E N O . E M E R G E N C Y T E L E P H O N E N O .
A