Current Intelligence Bulletin 3: Ethylene (EDB)

Department of Health, Education, and Welfare
Public Health Service
Center for Disease Control

National Institute for Occupational
Safety and Health
5600 Fishers Lane
Rockville, Maryland 20852

Dear Colleague:

The attached background material on ethylene dibromide has been prepared by the Office of Occupational Health Surveillance and Biometrics, National Institute for Occupational Safety and Health, to alert members of the occupational health community to new information on a potential occupational hazard.

Your comments and suggestions for changes to future reports are solicited.

[signature]
J. William Lloyd, Sc.D., Director
Office of Occupational Health
and Biometrics

Summary

A preliminary report from the National Cancer Institute (NCI) indicates that ethylene dibromide (EDB) is carcinogenic in laboratory rodents. Ethylene dibromide is a synthetic organic chemical with several industrial uses. Because of the potential risk of exposure in the work environment, the National Institute for Occupational Safety and Health (NIOSH) is alerting the occupational health community to these findings.

Introduction

In a memorandum of alert dated October 16, 1974, the Associate Director for Carcinogenesis of the National Cancer Institute (NCI) informed the DHEW Committee to Coordinate Toxicology and Related Programs of the possible carcinogenicity of ethylene dibromide. Subsequently, NIOSH was informed by the NCI of the preliminary findings in bioassay which suggest a strong carcinogenic activity of ethylene dibromide in both rats and mice producing squamous cell carcinomas of the stomach.

Background

Ethylene dibromide^* is a colorless, heavy, nonflammable liquid with a sweet odor. The odor is detectable at 10 ppm.^l It is slightly soluble in water and miscible with most solvents. It has a vapor pressure of 17.4 mm and a boiling point of 131°C.²

In 1921, the antiknock properties of tetra-alkyl lead compounds were discovered. To prevent the deposition of lead, a substance capable of reacting with the lead to aid its removal from the engine cylinder was needed. Ethylene dibromide was found to be such a substance. Today, the primary uses of EDB are in antiknock compounds for gasoline and in fumigants for grains, fruits, and vegetables. It is also used as a soil fumigant for the control of nematodes. It is used less frequently in fire extinguishers, gauge fluids, and as a special solvent and catalyst in organic synthesis.^3,4 About 300 million pounds are produced annually in this country. Approximately 50 percent of this is used in fuel additives ⁶; much of the remainder is used in fumigants. When commercially fumigated grains were sampled from storage bins and analyzed for residues of organic fumigants, EDB was found in a range less than 0.01 to 6.10 ppm. The lower volatility of EDB resulted in disproportionally higher residues relative to other commonly used, more volatile compounds. ⁷

Ethylene dibromide is strongly absorbed by wheat and wheat products. There is very little decomposition of the EDB or reaction with these materials at ordinary temperatures. On heating, a substantial proportion of the absorbed EDB undergoes decomposition to ethylene glycol and inorganic bromide. ⁸

Toxicity

Human

Direct contact with EDB causes irritation and injury to the skin and eyes. Exposure to the vapor has caused the development of respiratory tract inflammation along with anorexia and headache with recovery after discontinuance of exposure. Weakness and rapid pulse have been associated with EDB exposure as well as cardiac failure leading to death. ⁹

Oral ingestion of EDB has led to liver necrosis and kidney tubular damage. Other symptoms which may be encountered following ingestion include excitement, tinnitus (ringing in the ears), and severe protracted vomiting.^10,11

To date, there have been no published reports of any association between EDB and cancer in humans.

Animal

In laboratory rodents, the vapor of EDB has caused depression of the central nervous system, pulmonary irritation, and renal and hepatic damage. ^12,13

Oral administration of EDB to hens adversely influenced the production, size, and fertility of eggs.¹⁴ The semen from bulls given oral doses of EDB had low density and the spermatozoa had poor motility. Obligospermia and degeneration of the spermatozoa were observed.¹⁵ The spermicidal action of EDB is not direct but occurs during the process of spermatogenesis. ¹⁶ In addition, EDB has been shown to have mutagenic potential. ^17,18

The National Cancer Institute tested EDB by gastric intubation in both sexes of M6APS(OM) rats and C57BL-C3H mice. Among the animals treated with 40 mg/kg body weight of EDB administered in corn oil five times per week (for varying lengths of time 12 to 473 days); 70 of the 93 rats (76 percent) and 82 of the 94 mice (87 percent) developed squamous cell carcinomas of the stomach. No stomach tumors were observed among 22 untreated rats and 39 untreated mice. ^**

Stomach cancers were observed as early as ten weeks after initiation of EDB treatment. The tumor originated in the forestomach, invaded locally, and eventually metastisized throughout the abdominal cavity. No squamous cell carcinomas were observed in controls. ^19,20

Permissible Occupational Exposure

The current Occupational Safety and Health Administration, Department of Labor, Standard for EDB is 20 ppm as an 8 hour time weighted average; 30 ppm as an acceptable ceiling; and 50 ppm as a maximum peak with 5 minutes duration, based on the 1970 ANSI Z.37.31 Standard.⁽¹³⁾

Occupational Exposure

Estimated Numbers of Workers Exposed to Ethylene Dibromide by Industry ^***

Industry	No. Exposed
Fumigators and Exterminators	8,897
General Merchandising	110
Chemical Manufacturing	76
Petroleum Products Manufacturing	28
TOTAL	9,111 †

Producers and Suppliers

The following is a list of the major producers and suppliers of ethylene dibromide in the United States.

Producer	Location
Bromet Co. (Ethyl Corp.)	Magnolia, Arkansas
Dow Chemical	Bayeity, Michigan
Dow Chemical	Magnolia, Arkansas
Great Lakes Chemical Co.	El Dorado, Arkansas
Houston Chemical Co.	Beaumont, Texas
Michigan Chemical Co.	El Dorado, Arkansas

TOTAL Consumption @ 330 million lbs./yr.

Notes

* Synonyms: 1,2 dibromoethane; glycol dibromide, ethane; 1-2 dibromo; ethylene bromide. [return to text]

** Unpublished preliminary report issued by the NCI, 1974. Requests for further information should be directed to the NCI, Bethesda, Maryland. [return to text]

*** Projections based on preliminary data from the National Occupational Hazard Survey, Hazard Surveillance Branch, Office of Occupational Health Surveillance and Biometrics, NIOSH. This does not include exposures to trade name products. [return to text]

† Does not include approximately 650,000 persons employed in service stations with potential exposure to leaded gasoline. [return to text]

Bibliography

1. Encyclopedia of Occupational Health and Safety, International Labour Office, Geneva, Vol. I. pp. 384-859 1972
2. Hawley, G.G.: Condensed Chemical Dictionary, 8th ed., Van Nostrand Reinhold Company, New York, p. 364, 1971
3. Von Oettingen, W.F.: The Halogenated Hydrocarbons: and Potential Dangers, Public Health Service Reports No. 414, p. 1529 1958
4. Kirk-Thmer Encyclopedia of Chemical Technology: John Wiley and Sons, Inc. New York, Vol. 3, p. 751, 1964
5. Number not used.
6. Calculated from production figures for ethylene dibromide, tetra, alkyllead compounds, and gasoline given in Chemical Economics Handbook, op. cit., and the percentage composition of "Typical Antiknock" compounds given in Kirk-Othmer Encyclopedia of Chemical Technology, op. cit., Vol. 10, p. 476
7. McMahon, B.M.: of Commercially Fumigated Grains for Residues of Organic Fumigants. J of AOAC, 54:964, 1971
8. Heuser, S.G.: Residues in Wheat Products after Fumigation with Ethylene Dibromide. J Sci Food Agri, 12:103-15, 1961
9. Von Oettingen, loc. cit.
10. Olmstead, E.V.: Changes in Ethylene Dibromide Poisoning. Arch of Ind Health, 21:525-27, 1960
11. Encyclopedia of Occupational Health and Safety, loc. cit.
12. Thomas, B.G.H. and Yant, W.T.: Effects of Ethylene Dibromide, Public Health Reports, p. 370, 1927
13. Federal Register, Vol. 37, No. 202, Wednesday, October 18, 1972
14. Alumote, E., Nachtomi, E., Kempenich-Pinto, 0., Mandel, E., and Schindler, H.: Effects of Ethylene Dibromide in Feed on the Growth, Sexual Development and Fertility of Chickens, Poultry Sci, 47:1979-85, 1968
15. Amir, D. and Volcani, R.: The Effects of Dietary Ethylene Dibromide (EDB) on the Testes of Bulls, Fertility and Sterility, 18:144-48, 1967
16. Amir, D.: The Sites of Spermicidal Action of Ethylene Dibromide in Bulls, J Reprod Fet, 35:519-25, 1973
17. Buselmaier, W., Roeharborn, G., and Propping, P.: Investigations with Pesticides in Host-Medicated Assay and Dominant Lethal Test in Mice, Biol Ze Ntralbl, 91:311-25, 1972
18. DeSerres, F.J. and Malling, H.V.: Analysis of the AD-3 Mutants of Neurospora Crassa Induced by Ethylene Dibromide - A Commonly Used Pesticide, Newsletter Environ Mutagen Soc, 3:36-7, 1970
19. Olson, W.A., Habermann, R.T., Weisburgen, E.K., Ward, J.M., and Weisburger, J.H.: Induction of Stomach Cancer in Rats and Mice by Halogenated Aliphatic Fumigants, J Nat Cancer Inst, 51:1993-95, 1973
20. Ward, J.M. and Habermann, R.J.: of Stomach Cancer in Rats and Mice Induced with the Agricultural Chemicals Ethylene Dibromide and Dibromochloropropane, Labs Inst. 30:392, 1974