CURRENT INTELLIGENCE BULLETIN 30
EPICHLOROHYDRIN
October 12, 1978
TABLE OF CONTENTS
EPICHLOROHYDRIN
October 12, 1978
The National Institute for Occupational Safety and Health (NIOSH) recommends
that as a prudent measure, epichlorohydrin be handled in the workplace as if it
were a human carcinogen. This recommendation is based primarily on two recent
studies: a long term epidemiologic study showing significant increase in
respiratory cancer deaths of exposed workers, and an inhalation study showing an
increase in nasal carcinomas in rats. In addition, cytogenic studies of human
peripheral lymphocytes have shown a highly significant increase in chromosome
abnormalities in exposed workers. Pending further evaluation of its carcinogenic
potential, NIOSH believes it would be prudent to minimize occupational exposure to
epichlorohydrin.
NIOSH has prepared this Bulletin to advise you of these recent studies, their
implications for occupational health, and precautions for handling products
containing epichlorohydrin. We request that producers, distributors, and users
transmit this information to their customers and employees, and that professional
associations and unions inform their members.
Exposure Standards
The current Department of Labor, Occupational Safety and Health Administration
(OSHA) standard for occupational exposure to epichlorohydrin is 5 ppm (19
mg/cu m) as an 8-hour time-weighted average.1 Studies of carcinogenicity were
not available when this standard was developed.
In September 1976, NIOSH recommended an occupational exposure limit of 2
mg/cu m of air (approximately 0.5 ppm) determined as a time-weighted average
(TWA) concentration for up to a 10 hour work day in a 40 hour work week, and a
ceiling concentration standard of 19 mg/cu m (approximately 5 ppm) as determined
by a sampling time of 15 minutes.2 After a comprehensive
review of the literatures NIOSH concluded that risks from exposure to epichlorohydrin may
include carcinogenesis, mutagenesis and sterility, as well as damage to the kidneys,
liver, respiratory tract, and skin. Since most of the evidence on adverse
effects of epichlorohydrin was obtained from animal experiments which were
inadequate to determine scientifically acceptable exposure limits, the 1976 NIOSH
recommendation was based on professional judgement which quantitatively
considered the cumulative toxic effects.
Production, Uses, and Occupational Exposures
Epichlorohydrin is a liquid at room temperatures. In 1978, domestic annual
production capacity was 470 million pounds. An important constituent of epoxy
resin is synthesized by alkylating bisphenol A with epichlorohydrin.2
Epichlorohydrin is used in the manufacture of epoxy resins, surface active agents,
pharmaceuticals, insecticides, agricultural chemicals, textile chemicals, coatings,
adhesives, ion-exchange resins, solvents, plasticizers glycidyl esters, ethynylethylenic
alcohol and fatty acid derivatives.
According to the NIOSH National Occupational Hazard Survey (NOHS),3 an
estimated 85,000 workers are potentially exposed to epichlorohydrin in the
workplace. Table 1 lists occupations and industries in which a potential exists for
exposure to epichlorohydrin. The NOHS survey data were collected during 1972 to
1974 from a sample of approximately 5,000 businesses employing nearly 900,000
workers. 1970 Census figures were used in extrapolating the sample data to the
working population employed in industries covered by the Occupational Safety and
Health Act of 1970. The potential exposure estimates include data on actual
observations of the use of the specific chemical or the use of a trade name product
known to contain the chemical as well as additional observations of generic
formulations (trade name products suspected of containing the chemical).
Table 1. Some Occupations and Industries Which Use Epichlorohydrin
Occupations a
| assemblers; miscellaneous specified machine operatives; aircraft
machinists; construction and maintenance painters; miscellaneous
operatives; chemists; mining operatives; painters of manufactured
articles; sheetmetal workers and tinsmiths; pattern and model
matters except paper
|
Industries b
| chemicals and allied products; transportation equipment; instruments
and related products; transportation by air; electrical
equipment and supplies; special trade contractors; miscellaneous
repair services; rubber and plastics not elsewhere classified;
machinery, except electrical; stone, clay, and glass products
|
(a) Standard occupational titles from the Bureau of the Census4
(b) Standard Industrial titles from the Standard Industrial Classification Manual.5
Human Carcinogenicity
A statistically significant (p<.05 increase in deaths due to respiratory cancer has been observed in a long-term epidemiologic study conducted on workers exposed to epichlorohydrin at two facilities of the Shell Chemical Company.6 The data were
analyzed by Dr. Philip Enterline of the University of Pittsburgh.7,8 There were
864 workers identified as having been occupationally exposed to epichlorohydrin for
6 months or more, before January 1, 1966. Ninety-eight percent of the workers
were traced as of December 31, 1976. For men estimated to have had moderate to
heavy exposure who were followed for 15 years or more, observed deaths were also
greater than those expected for the categories of all cancers, leukemia, and
suicide, although those differences were not statistically significant. Information
was not available for most workers on smoking history, or the extent of exposure to
other chemicals.9 NI0SH feels that the study results are suggestive of a
carcinogenic effect of epichlorohydrin on humans, and deserve attention.
The Dow Chemical Company has informed NIOSH that it is currently conducting a
mortality study of workers engaged in the manufacture and conversion of
epichlorohydrin.10 Dow estimates that the results will be made available
November, 1978.
Animal Carcinogenicity
In ongoing inhalation studies, rats exposed to epichlorohydrin have shown a
statistically significant increase in nasal cancer (p <.05).11
In experiments initiated under Dr. Sidney Laskin and continued under Dr. Norton Nelson at the
New York University Institute of Environmental Medicine, 140 rats have been
exposed to 100 ppm epichlorohydrin for 6 hours/day, 5 days/week, for 30 days, with
subsequent lifetime observation. Fifteen of the animals have died with
pathologically confirmed squamous cell nasal cancinoma.11
Another animal developed a nasal papilloma. No spontaneous nasal cancer was seen in a group of
50 controls. Of another group of 100 animals exposed to 30 ppm of epichlorohydrin
for 6 hours/day, 5 days/week, in a chronic lifetime study one animal has developed
a papilloma of the larynx, another has developed a nasal squamous cell carcinoma.12
In contrast, no spontaneous nasal carcinomas were seen in the 50 animal
control group.
Further information on previous studies that investigated the other evidence
relating to carcinogenicity of epichlorohydrin can be found in the NIOSH
epichlorohydrin criteria document.2,13
Human Mutagenicity
Epichlorohydrin has been shown to induce a significant increase in chromosomal
aberrations found in the white blood cells of workers occupationally exposed to
epichlorohydrin. In 1979 Kucerova et al.14 conducted a prospective cytogenetic
study of 35 workers occupationally exposed to epichlorohydrin. Each worker served
as his own control. After exposure for one year, these workers showed a significant
increase in chromosomal aberrations. After two years of exposure to
epichlorohydrin, the increase in chromosomal aberrations was significant at the
p <.0001 level.
In 1976, Sram et al.15 found chromosome abnormalities in human peripheral
lymphocytes exposed in vitro to epichlorohydrin. They concluded that a genetic
risk for man exists following exposure to epichlorohydrin. A quantitative risk was
not estimated.
Other Toxic Effects
Epichlorohydrin is a highly toxic substance which is easily absorbed through the
skin. Skin contact with epichlorohydrin can cause severe chemical burns, although
the effects may not appear until sometime after exposure. The latent period can
range from several minutes to several days, depending on the duration and intensity
of exposure. Allergic response has been noted.16 Exposure to epichlorohydrin
vapor induces transient burning of the eyes and nasal passages at concentrations as
low as 20 ppm. Exposure to high concentrations (100 ppm) leads to pulmonary
edema (fluid accumulation in the lung) and kidney problems in laboratory animals.
A comprehensive discussion of the toxic effects is found in the NIOSH
epichlorohydrin criteria document. Table 2 summarizes the reported toxic
effects in humans at varying exposure levels.
Table 2. Other Toxic Effects of Epichlorohydrin on Humans.2
Route of
Exposure
| Effect
|
dermal
| burning sensation, redness, swelling, red papules, itching, blisters,
skin erosion, enlarged lymph nodes
|
inhalation
| burning of the eyes, nose and throat; cough; chest congestion; running
nose; eye tenderness; headache followed by nausea; vomiting;
facial swelling; dyspnea
|
Exposure to epichlorohydrin has been shown to induce sterility in rats,2 and a
fertility study has been conducted in male workers exposed to epichlorohydrin.17
While the study concluded that exposure to epichlorohydrin did not decrease sperm
counts or affect hormonal activity in the workers, the data were not analyzed
statistically.
NIOSH Recommendations
In light of the statistically significant increase in respiratory cancer seen in
workers exposed to epichlorohydrin, and the statistically significant increase in
nasal carcinomas seen in rat inhalation studies, as well as the chromosomal
aberrations seen in the peripheral lymphocytes of exposed workers, NIOSH
recommends that epichlorohydrin be treated in the workplace as if it were a human
carcinogen. Pending further evaluation of its carcinogenic potential NIOSH
believes it would be prudent to minimize occupational exposure to epichlorohydrin.
Exposures should be limited to as few employees as possible while workplace
exposure should be minimized with engineering and work practice controls. In
particular, skin exposure should be avoided.
|
[signature]
J. Michael Lane, M.D.
Acting Director
|
References
- U.S. Department of Labor, Occupational Safety and Health Administration:
Occupational Safety and Health General Industry Standards.
Publication 2206, 29 CFR 1910-1000, Washin ton, D.C. (1976)
- U.S. Department of Health, Education, and Welfare, Public Health Service,
Center for Disease Controling National Institute for Occupational Safety and
Health. Criteria for a Recommended Standard .... Occupational Exposure to
Epichlorohydrin. Washington, D.C. (1976).
- NIOSH National Occupational Hazard Survey (NOHS): Personal
communication to the NIOSH Technical Evaluation and Review Branch,
Office of Extramural Coordination and Special Projects (1978).
- U.S. Bureau of the Census: 1970 Census of Population, Alphabetical Index of
Industries and Occupations. Washington, D.C. (1971).
- Bureau of the Budget: Standard Industrial Classification Manual. Washington, D.C. (1967).
- Enterline, P.: Letter from P. Enterline, Ph.D., Department of Biostatistics,
University of Pittsburgh to R. E. Joyner, M.D., Corporate Medical Director,
Shell Oil Company, July 31, 1978.
- Enterline, P.: Updated Mortality in Workers Exposed to Epichlorohydrin,
unpublished report to the Shell Oil Company, July 31, 1978.
- Enterline, P.: Mortality in Workers Exposed to Epichlorohydrin, unpublished
report to the Shell Oil Company, August 31, 1977.
- Joyner, R.E.: Letter from R.E. Joyner, M.D., Corporate Medical Director,
Shell Oil Company to J. Michael Lane, M.D., Acting Director, NIOSH,
August 7, 1978.
- Walker, R.C.: Letter from R.C. Walker, Manager, The Dow Chemical
Company, to Vernon E. Rose, Ph.D., Director, Division of Criteria
Documentation and Standards Development, NIOSH, August 29, 1978.
- New York University Institute of Environmental Medicine: Personal
communication to the NIOSH Technical Evaluation and Review Branch,
Office of Extramural Coordination and Special Projects, (1978).
- Nelson, N.: Letter to the Office of the Director, NIOSH, June 23, 1978,
updating the letter of March 28, 1977.
- Van Duuren, B.B., B. M. Goldschmidt, C. Katz, I. Seidman, and J. S. Paul:
Carcinogenic Activity of Alkylating Agents. Journal of the National Cancer
Institute 53: 695-700 (1974).
- Kucerova, M., V. S. Zurkov, Z. Polvkova, and J. E. Ivanova: Mutagenic Effect
of Epichlorohydrin. II. Analysis of Chromosol Aberrations in Lymphocytes of
Persons Occupationally Exposed to Epichlorohydrin. Mutation Research, 48:
355-360 (1977).
- Sram, R.J., M. Cerna, and M. Kucerova: The Genetic Risk of Epichlorohydrin
as Related to the Occupational Exposure. Biologisches Zentralblatt 95: 451-
462 (1976).
- U.S. Department of Health, Education, and Welfare, Public Health Service,
Center for Disease Control, National Institute for Occupational Safety and
Health: Occupational Diseases: A Guide to Their Recognition. Washington,
D.C. (1977).
- Whorton, D., T.H. Milby, and R.L. Davis: Testicular Function Among ECH
Workers at Shell Deer Park and Norco Facilities. Unpublished report to the
Shell Oil Company from Environmental Health Associates, August 22, 1978.
SUGGESTED GUIDELINES FOR MONITORING AND CONTROLLING EMPLOYEE
EXPOSURE TO EPICHLOROHYDRIN
NIOSH recommends that it would be prudent to handle epichlorohydrin in the
workplace as if it were a human carcinogen. Exposure to epichlorohydrin should be
limited to as few employees as possible, and workplace exposure levels should be
minimized. The area in which it is used should be restricted to only those
employees essential to the process or operation and these employees should be
adequately protected.
Exposure Monitoring
A detailed sampling, and analytical method for epichlorohydrin exposure
measurements is described in the NIOSH Manual of Analytical Methods, Second
Edition1 as NIOSH method #S118 in Volume 2.
Initial and routine employee exposure surveys should be made by competent
industrial hygiene and engineering personnel. These surveys are necessary to
determine the extent of employee exposure and to ensure that controls are
effective.
The NIOSH Occupational Exposure Sampling Strategy Manual,2 may be helpful in
developing efficient programs to monitor employee exposures to epichlorohydrin.
The manual discusses determination of the need for exposure measurements
selection of appropriate employees for exposure evaluation and selection of
sampling times.
Employee exposure measurements should primarily consist of 8-hour TWA (time-weighted
average) exposure estimates calculated from personal or breathing zone
samples (air that would most nearly represent that inhaled by the employees). In
addition, short term samples should be taken during periods of maximum expected
exposure by using all available knowledge regarding the area, employee work
procedures, and process. Area and source measurements may be useful to
determine problem areas, processes, and operations.
Controlling Employee Exposure
There are four basic methods of limiting employee exposure to epichlorohydrin.
None of these is a simple industrial hygiene or management decision and careful
planning and thought should be used prior to implementation.
The substitution of an alternative material with a lower potential health risk is one
method. However, extreme care must be used when selecting possible substitutes.
Alternatives to epichlorohydrin should be fully evaluated with regard to possible
human effects. Unless the toxic effects of the alternative have been thoroughly
evaluated a seemingly safe replacement, possibly only after years of use, may be
found to induce serious health effects.
The most effective control of epichlorohydrin where feasible, is at the source of
contamination by enclosure of the operation and/or local exhaust ventilation.
Guidelines for selected processes and operations can be found in the NIOSH
Recommended Industrial Ventilation Guidelines.3
If feasible, the process or operation should be enclosed with a slight vacuum so that
any leakage will result in the flow of external air into the enclosure.
The next most effective means of control would be a well designed local exhaust
ventilation system that physically encloses the process as much as possible, with
sufficient capture velocity to keep the contaminant from entering the work
atmosphere.
To ensure that ventilation equipment is working properly, effectiveness (e.g., air
velocity, static pressure or air volume) should be checked at least every three
months. System effectiveness should be checked soon after any change in
production, process, or control which might result in significant increases in
airborne exposure to epichlorohydrin.
A third alternative is the isolation of employees. It frequently involves the use of
automated equipment operated by personnel observing from a closed control booth
or room. The control room is maintained at a greater air pressure than that
surrounding the process equipment so that air flow is out of, rather than into, the
room. This type of control will not protect those employees that must do process
checks, adjustments maintenance and related operations.
Personal Protective Equipment
The least preferred method is the use of personal protective equipment. This
equipment which may include respirators goggles, gloves, etc., should not be used
as the only means to prevent or minimize exposure during routine operations.
Exposure to epichlorohydrin should not be controlled with the use of respirators
except:
- During the time period necessary to install or implement engineering or work
practice controls; or
- In work situations in which engineering and work practice controls are technically
not feasible; or
- For maintenance; or
- For operations which require entry into tanks or closed vessels; or
- In emergencies.
Only respirators approved by the National Institute for Occupational Safety and
Health (NIOSH) under the provisions of Federal regulations 30 CFR 11 should be
used. Refer to Cumulative Supplement June 1977, NIOSH Certified
Equipment4
for a listing of NIOSH-approved respirators. Note that the use of faceseal
coverlets or socks with respirators voids NIOSH approvals.
Quantitative faceseal fit test equipment (such as sodium chloride, dioctyl
phthalate, or equivalent) should be used. Refer to NIOSH's A Guide to Industrial
Respiratory Protection5 for guidelines on appropriate
respiratory protection programs.
In addition, proper maintenance procedures, good housekeeping in the work area,
and employee education are all vital aspects of a good control program. Employees
should be informed as to the nature of the hazard, its control, and appropriate
personal hygiene procedures.
References for Suggested Guidelines
- NIOSH Manual of Analytical Methods, 2nd Edition, Vol. 1:
GPO #017-033-00267-3, $8.75: Vol. 2: GPO #017-033-00260-6, $9.75: Vol. 3:
GPO #017-033-0247-9, $9.00.
- NIOSH Occupational Exposure Sampling Strategy Manual,
GPO #017-033-00247-9, $2.75.
- NIOSH Recommended Industrial Ventilation Guidelines, GPO #017-033-00136-
7, $3.90.
- NIOSH Cumulative Supplement June 1977, NIOSH Certified Equipment,
NIOSH #77-195, no charge.
- A Guide to Industrial Respiratory Protection, GPO #017-033-00153-7, $2.30.
GPO publications must be ordered from:
| Superintendent of Documents
U.S. Government Printing Office
Washington, D.C. 20402
|
Reference #4 can be ordered from:
| Publications Dissemination, DTS
NIOSH
4676 Columbia Parkway
Cincinnati, Ohio 45226
|
IDENTIFIERS AND SYNONYMS FOR EPICHLOROHYDRIN
Chemical Abstracts Service Registry Number: 106-89-8
NIOSH RTECS Number: TX4900000
Chemical Formula: C3H5OCl
1-Chloro-2,3-epoxypropane | Epichlorohydrin
|
3-Chloro-1,2-epoxypropane | a-Epichlorohydrin
|
3-Chloro-1,2-propylene oxide | 1,2-Epoxy-3-chloropropane
|
(Chloromethyl)ethylene oxide | 2,3-Epoxypropyl chloride
|
(Chloromethyl)oxirane | Glycerol epichlorohydrin
|
2-Chloromethyl oxyrane | Glycidyl chloride
|
3-Chloropropene-1,2-oxide | Oxirane, (chloromethyl)-
|
Chloropropylene oxide | Oxirane, 2-(Chloromethyl)-
|
y-Chloropropylene oxide | Propane, 1-chloro-2,3-epoxy-
|
ECH | SKEKhG
|
ECHH
|
CUMULATIVE LIST OF
NIOSH CURRENT INTELLIGENCE BULLETINS
1. Chloroprene | January 20, 1975
|
2. Trichloroethylene (TCE) | June 6, 1975
|
3. Ethylene Dibromide (EDB) | July 7, 1975
|
4. Chrome Pigment | June 24, 1975
October 7, 1975
October 8, 1976
|
5. Asbestos - Asbestos Exposure during Servicing
of Motor Vehicle Brake and Clutch Assemblies | August 8, 1975
|
6. Hexamethylphosphoric Triamide (HMPA) | October 24, 1975
|
7. Polychlorinated Biphenyls (PCBS) | November 3, 1975
August 209 1976
|
8. 4,4'-Diaminodiphenylmethane (DDM) | January 30, 1976
|
9. Chloroform | March 15, 1976
|
10. Radon Daughters | May 11, 1976
|
11. Dimethylcarbamoyl Chloride (DECC)
Revised | July 7, 1976
|
12. Diethylcarbamoyl Chloride (DECC) | July 7. 1976
|
13. Explosive Azide Hazard | August 16, 1976
|
14. Inorganic Arsenic - Respiratory
Protection | September 27,1976
|
15. Nitrosamines in Cutting Fluids | October 6, 1976
|
16. Metabolic Precursors of a Known Human Carcinogen, Beta-Naphthylamine | December 17, 1979
|
17. 2-Nitropropane | April 25, 1977
|
18. Acrylonitrile | July 1, 1977
|
19. 2,4-Diaminoanisole in Hair and Fur Dyes | January 13, 1978
|
20. Tetrachloroethylene (Perchloroethylene) | January 20, 1978
|
21. Trimellitic Anhydride (TMA) | February 3, 1978
|
22. Ethylene Thiourea (ETU) | April 11, 1978
|
23. Ethylene Dibromide and Disulfiram Toxic Interaction | April 11, 1978
|
24. Direct Black 38, Direct Blue 6, and Direct Brown 95 Benzidine Derived Dyes | April 17, 1978
|
25. Ethylene Dichloride (1,2-Dichloroethane) | April 19, 1978
|
26. NIAXI Catalyst ESN | May 22, 1978
|
27. Chloroethanes - Review of Toxicity | August 21, 1978
|
28. Vinyl Halides - Carcinogenicity | September 21,1978
|
29. Glycidyl Ethers | October 12, 1978
|
30. Epichlorohydrin | October 12, 1978
|
|
Copies of this and other NIOSH documents are available from:
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Cincinnati, OH 45226-1998
FAX (513) 533-8573
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