COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIA
ENVIRONMENTAL TOXICOLOGY NEWSLETTER

Vol. 2 No. 1 August 3, 1981

Ethylene Dibromide and Methyl Bromide

The spread of the Mediterranean Fruit Fly throughout the Santa Clara Valley has raised the possibility that large quantities of California fruit will have to be fumigated prior to export to other states. Two of the most commonly used fumigants for this purpose are ethylene dibromide and methyl bromide. If widespread fumigation becomes a reality, you may receive requests for information about these chemicals. This newsletter is a cursory review of some considerations of the toxicology of EDB and MB. It is not a complete review or analysis, and the principal focus will be on EDB. I will be glad to provide more detailed information about specific toxicological data in response to specific requests.

Introduction

Ethylene dibromide (EDB) is a colorless, heavy, non-flammable liquid that has a sweet odor that is detectable at 10 ppm. Methyl bromide (MB) is a colorless, odorless, non-flammable gas. Both of these compounds are highly reactive alkylating agents. About 90% of the EDB produced in the country has been used as a lead scavenging component of gasoline by converting lead oxides to lead halides which pass out of the engine with exhaust. One of the chief sources of EDB in the environment is evaporation from fuel tanks and carburetors of cars operated on leaded fuel. Agricultural uses of EDB account for approximately 10% of the EDB produced in this country.

METHYL BROMIDE Toxicology

The following information about the acute toxicity of MB and EDB was taken directly from the California Department of Food and Agriculture Pesticide Safety Information Series.

Acute Toxicity

1. Acute Poisoning
   • Direct contact with skin and eyes: Contact of the skin with liquid methyl bromide or high concentrations of its vapors may cause an itching and prickling of the skin followed by reddening and later formation of vesicles and blisters which heal slowly. Severe burning of the cornea may result from contact of the liquid with the eyes.
   • Inhalation and/or skin absorption of vapors: These effects are extremely variable. It is difficult to list all symptoms or to say with certainty which ones may appear first. The effects mentioned here may occur singly or more than one may be present. Their severity is not necessarily an indication of the severity of poisoning. Early symptoms may include blurred or double vision, nausea, vomiting, dizziness, headache, inflammation of the eyes, blurred and hesitant speech, incoordination of muscular movement, and elevation of body temperature. Fainting spells, unconsciousness or mild depression may also be present.
     Breathing may become difficult or stop entirely. It has also been reported that exposed people note occasional changes in the taste of food. Trembling, muscular twitching and convulsions are not unusual.
   • Delay in appearance of symptoms of acute poisoning: THE ONSET OF SYMPTOMS OF ACUTE POISONING MAY BE DELAYED 4 TO 6 HOURS OR MORE. THIS CHARACTERISTIC OF METHYL BROMIDE POISONING CREATES A VERY DANGEROUS SITUATION. AN INDIVIDUAL MAY RECEIVE A POTENTIALLY FATAL DOSE, HAVE ONLY MILD SYMPTOMS AT FIRST AND MAY EVEN SHOW IMPROVEMENT FOR SEVERAL HOURS. SERIOUS SIGNS AND SYMPTOMS MAY THEN DEVELOP AND THE INDIVIDUAL MAY DIE.
2. Chronic Poisoning
   • Local effects on skin from repeated skin exposure to low concentrations: Pimples on the face, arms, back and chest (identical in appearance to acne seen most frequently in teenage children) may be an indication of repeated skin exposure.
   • Chronic systemic effect of repeated inhalation or absorption through the skin of low concentrations of ethyl bromide.
   • All of the signs and symptoms previously listed under "acute" effects may occur in a person with chronic poisoning. Signs of fatigue and appetite loss may develop. Signs of disturbance of nerve functioning may be particularly marked, so that a person so exposed may appear to be drunk or appear to have a change in personality.
   • Chronic systemic effects from a single substantial exposure: Nerve damage effects can last for years resulting in vision and walking difficulties.

ETHYLENE DIBROMIDE

HUMAN POISONING

Immediate symptoms of human poisoning could include headaches, dizziness, nausea, weakness, and, in severe cases, liver and kidney damage; central nervous system depression can occur within 48 hours after ingestion. Death from EDB overexposure appears to be due to breathing failure or heart failure complicated by excess fluid in the lungs. Breathing excess amounts causes delayed lung damage and excess fluid in the lungs. EDB is a severe irritant. Contact of the liquid with skin and other tissues can cause redness, swelling, tissue destruction, and general toxicity. In studies in animals, EDB is a significant producer of cancer; it is a mutagen and a teratogen, and it interferes with the production of sperm in some male animals such as the calf.

INFORMING EMPLOYEES OF HAZARDS FROM ETHYLENE DIBROMIDE

All persons in any area where EDB is used should be informed of the hazards, symptoms of poisoning, effects of overexposure, and proper conditions and precautions concerning safe use and handling of EDB. They must be advised of the need to avoid exposure to EDB within 30 days of taking the drug antabuse or exposure to Thiram. Employees must be told that EDB has been shown to be a mutagen, a teratogen, a carcinogen, and a reducer of sperm counts in animals, and is suspect of being able to cause these effects in man if safety precautions are not followed. A continuing educational program should be instituted to ensure that all workers have current knowledge of job hazards, proper maintenance procedures and cleanup methods, and correct use of respiratory protective equipment and protective clothing.

The information explaining the hazards of working with EDB should be kept on file and readily accessible to the worker at all places of employment where EDB is used.

Skin Protection

If any procedure involving EDB could result in skin exposure, gloves, apron, boots, respirator, and eye protection should be worn. NO PROTECTIVE CLOTHING MATERIALS ARE COMPLETELY IMPERVIOUS TO THE CONCENTRATED FORM OF EDB. Materials such as Neoprene, Tyvek, and Nitrite give reasonably good protection if spills of EDB are immediately washed off. Other materials may be used if they give equal or better protection. All protective gear should be well-aired and inspected for defects prior to reuse.

MEDICAL ASSISTANCE SHOULD BE OBTAINED FOLLOWING FIRST AID TREATMENT IF:

• EDB has been swallowed.
• High vapor concentrations of EDB have been inhaled.
• EDB has splashed into the eye, and it still hurts after washing for 15 minutes.
• Large areas of skin have been contaminated.
• A person has become ill or unconscious while working with EDB.

ONCE SIGNIFICANT EXPOSURE TO EDB HAS OCCURRED, THE EXPOSED PERSON MUST BE TAKEN TO A PHYSICIAN.

(California Department of Food and Agriculture Pesticide Safety Information Series)

In mammals, EDB is metabolized by oxidative dehalogenation to 2-bromoethanol, which is further oxidized to bromoacetaldehyde. These reactions have been confirmed by laboratory studies. The bromoacetaldehyde intermediate is probably rapidly oxidized to the corresponding bromoacetic acid by aldehyde dehyrogenase.

Disulfiram (Antabuse) is an inhibitor of aldehyde dehydrogenase that is used in human alcohol dependence aversion therapy. Disulfiram has been shown to greatly enhance the carcinogenicity of EDB in rats. It is likely that it would in humans too, thus exposure to EDB should be avoided within 30 days of taking Disulfiram, or being exposed to Thiram (a pesticide which is chemically and pharmacologically similar to Disulfiram).

Chronic Toxicity

Because methyl bromide and ethylene dibromide are alkylating agents, they both have the potential for carcinogenicity, mutagenicity and teratogenicity. Experimental evidence supports this. Ethylene dibromide has been shown to be carcinogenic to rats and mice when it was given orally at maximal tolerated dose levels. Ethylene dibromide has been shown to cause decreased fertility in animals. In hens, EDB decreases egg size and results in infertility and cessation of egg laying. In rats and bulls, EDB caused a reversible inhibition of spermatogenesis. Because of indications that EDB might have an anti-spermatogenic effect, one manufacturer of EDB (Ethyl Corporation) undertook a study to determine the effects of occupational exposure to EDB on sperm counts in exposed workers. In their facility, time weighted average exposure to EDB was less than 5 ppm. Their study showed that in their facilities, EDB exposure did not have an adverse effect on sperm count. In the same studies, the incidence of cancer in persons occupationally exposed to EDB was also examined. There was no indication that occupational EDB exposure increased the likelihood of cancer in the individuals studied. This observation should not be taken as a clean bill of health for EDB with respect to human carcinogenesis because the sample size was small (53 workers). Time will tell.

Residues in Food

The mechanism of fumigant action of MB and EDB is the alkylation and inactivation of macromolecules essential to life. Both of the compounds are non-selective and will kill practically all forms of life. Following fumigation there are three types of residues left in fumigated products. The first is unreacted MB or EDB, the second is alkylated macromolecules, and the third is inorganic bromide ion. The alkylated macromolecules are of no toxicological significance. Following ingestion they will be metabolized like other food nutrients. The unreacted MB or EDB present in foods are potential sources of exposure to workers and consumers. Because of the high volatility of MB, virtually none is found in fumigated foods 24 hours after fumigation. Ethylene dibromide is less volatile than MB, and depending on storage conditions, unreacted EDB can be found in fruits for 14 days or longer following fumigation exposure. The temperature at which fruit is held following fumigation is the main determinant of the rate of dissipation of unreacted EDB. At high temperatures EDB dissipates faster than at low environmental temperatures. The dissipation of EDB from fumigated fruit could be a possible source of human exposure in unventilated areas. Studies have also shown that cartons which hold the fruit during fumigation may retain higher levels of EDB for a longer period of time than the fruit itself and thus are another potential source of exposure in confined areas. Waxed containers retain EDB longer than untreated containers.

Inorganic bromide is a potentially toxic residue that forms in fruits and soil following EDB fumigation. The inorganic bromide ion is a byproduct of the reaction of the alkylation of macromolecules by EDB. In the past bromide ion was used medicinally as a sedative, however, it has fallen from favor due to its toxicity. The toxic effects of bromide ion (known as bromism) includes central nervous system depression, impaired memory, dizziness, hallucinations, mania, and skin eruptions (similar to acne). In humans it takes gram quantities of bromide ion to produce these toxic effects. The acceptable daily intake of bromide is said to be 7 mg/kg body. For a 70 kg person, this is equivalent to 7 kg of food containing 50 ppm bromide or 2.3 kg of food containing 150 ppm bromide. In studies in which fruit was fumigated with EDB or MB, fruit residues rarely exceeded 10 ppm and the bromide concentration was greater in the peel than in the pulp. The tolerance levels for bromide in citrus fruit pulp is set at 25 ppm. It is doubtful that EDB or MB fumigation of fruits in California will result in levels of bromide exceeding this concentration.

Permissible Exposure Limits

The current OSHA environmental standard for EDB is 20 ppm for an 8-hour time-weighted exposure for a 40 hour work week. In 1977 NIOSH recommended a ceiling environmental exposure limit of .13 ppm EDB for 15 minutes.

Environmental Fate

Because of the ubiquitous use of ethylene dibromide as a fuel additive, very low levels of EDB can be found in air samples throughout the environment. These ambient air concentrations are generally in the range of 0.00001 to 0.00005 ppm. The limited data available suggests that EDB degrades at moderate rates in soil and water. The principle breakdown products again would be the hydrolysis product 2-bromoethanol, bromide ion and alkylated macromolecules. 2-Bromoethanol would probably be as toxic to mammals as the parent compound EDB. An air sample taken a mile away from a USDA fumigation center detected 96 micrograms/cubic meter of ethylene dibromide (approximately 0.01 ppm).

Conclusions:

Although methyl bromide and ethylene dibromide are highly toxic chemicals, experience has shown that they can be used safely. I suspect there may be public concern if fumigation facilities are located in highly populated areas. Because of the mechanism of toxic action of these chemicals, I think that human exposure should be minimized as much as possible. Air monitoring of EDB and MB levels in areas close to fumigation sites would be very useful.

A list of the references that I used for this newsletter is available upon request.

Arthur L. Craigmill, Ph.D.
Extension Toxicologist
Environmental Toxicology and Veterinary Extension
University of California
Davis, CA 95616
(530) 752-1142