COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIAENVIRONMENTAL TOXICOLOGY NEWSLETTER

COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIA
ENVIRONMENTAL TOXICOLOGY NEWSLETTER

In the last four months since the last Environmental Toxicology Newsletter was published, there have been many developments to report. This issue contains reports of a range of interesting topics chosen because they represent major areas of public concern, or to broaden the perspective of the reader. All too often we may be suffering from a condition that could be called "toxics myopia" which I will define as a tendency to overemphasize one aspect or area of toxicology and miss the larger picture. It also marks the first appearance of two new guest authors, Helene Swenerton, and John Lowe. As always, I appreciate feedback from readers as to the relevance of the information to your needs. Thank you.

Written by John Lowe
Environmental Hazards Specialist
CDFA Worker Health and Safety Unit

Among the fumigants available for rodent control, methyl bromide deserves the greatest respect from its users. Methyl bromide can cause a number of toxic effects depending on the doses and routes of exposure. Exposure to the skin or eyes can result in severe burns and methyl bromide can readily penetrate protective clothing and skin. Inhalation of the vapors results in a variety of neurological effects, including tremors, twitching, seizures or convulsions, with the onset of symptoms possibly being delayed from 3 to 36 hours. Workers exposed to methyl bromide have reported symptoms of nausea, vomiting and headaches. Methyl bromide has been shown to be mutagenic in microbial assays, hence is potentially carcinogenic. An additional hazard is that methyl bromide is odorless, providing no warning of exposure. Based on the human health hazards, methyl bromide is a restricted use pesticide.

Methyl bromide is used in vertebrate control programs operated by the county agricultural commissioners. Rodent burrow fumigation is used as a cleanup technique following baiting, trapping and habitat modification, so employee exposure is intermittent. Recently, the Worker Health and Safety Unit of the California Department of Food and Agriculture completed an exposure survey of county employees using methyl bromide for rodent fumigation. This survey was intended to determine if respiratory protection (specifically, self-contained breathing-apparatus) was required for employees performing this activity. Air sampling results showed that employee exposures ranged from 0.07 to 0.5 ppm calculated on 8-hour time-weighted-averages.

Potential exposure periods ranged from two to three hours per 8- hour day, with exposure during the remainder of the employees work day assumed to be zero. Short-duration (5 minute) sampling results were from none detectable to 14 ppm, with a majority of the results between 0.1 to 0.9 ppm.

These concentrations are below currently enforced exposure standards for methyl bromide. The Cal-OSHA Permissible Exposure Limit is 15 ppm based on an 8-hour time-weighted-average, with one 5 minute excursion limit of 25 ppm permitted each 8-hour day. These limits represent concentrations to which nearly all workers may be exposed daily during a 40 hour workweek for a working lifetime without adverse effect.

Based on the survey results, it was concluded that respiratory protection was not required, however, other potential health and safety hazards were identified. Since fumigations are often performed in isolated areas, the occurrence of an equipment malfunction (releasing liquid or high vapor concentrations) can be hazardous to an employee working alone. Employees should work in pairs to minimize this hazard. Vehicles used for fumigation should carry decontamination water, in case of eye or skin exposure. Employees should attempt to keep the vehicle near their work area, for a faster response in the event of an accident. Eye protection (goggles or a faceshield) should be worn when using methyl bromide. Employee training should include recognition of the symptoms of exposure, first aid procedures and safe handling of application equipment.

A copy of the exposure survey report can be obtained free of charge from the Worker Health and Safety Unit. Ask for report number HS-1238. Anyone interested further in methyl bromide and its associated hazards is encouraged to call or write to:

California Department of Food and Agriculture
Worker Health and Safety Unit
Room A-413, 1220 N Street
Sacramento, California 95814
(916) 445-8474

Vietnam veterans' risks for fathering babies born with serious structural birth defects were assessed using a case- control study. Case-group babies - those with serious structural defects - were born during 1968 through 1980 and registered by CDC's Metropolitan Atlanta Congenital Defects Program (MACDP). To be included in the registry, a baby's defects must have been diagnosed during the first year of life and recorded on a hospital chart by a physician. The use of MACDP as the source of cases precluded analysis of other reproductive outcomes in the fathers or functional deficits, such as mental retardation, in the babies.

Control-group babies - those born without defects - were chosen from among 323,421 babies who were born in the same metropolitan area to resident mothers during the same period. They were frequency-matched to the case-group babies by race, year of birth, and hospital of birth. A total of 7,133 case- group babies and 4,246 control-group babies were eligible for the study. The decision to include fewer control-group babies than case-group babies was based on a review of the anticipated statistical power of the study. Information about paternal military service in Vietnam was obtained during 1982 and 1983 through telephone interviews with the parents of the case- and control-group babies. Vietnam veteran fathers were asked if they believed they had been exposed to herbicides, such as Agent Orange. In addition, a five-level "Exposure Opportunity Index" (EOI) was defined based on activities that may have provided an opportunity for exposure to Agent Orange. Vietnam veteran fathers were given subjective scores by the staff of the Army Agent Orange Task Force reflecting their presumed opportunities for exposure to Agent Orange; the EOI scores were assigned on the basis of time and places of service in Vietnam and occupational duties. Scores were assigned without knowledge of the case/control status of the fathers. Both parents were questioned about a wide variety of other potential risk factors for birth defects. In addition, Vietnam veteran fathers were asked whether they had contracted malaria in Vietnam and whether they had taken malaria chemoprophylaxis (preventative drug therapy) there.

The estimated relative risk of Vietnam veterans' fathering babies with defects when all types of defects are combined was 0.97 (95% confidence limits 0.83-1.14). (Note that the relative risk would have to be greater than one if Vietnam vets have a greater risk.) With few exceptions, the estimated relative risks of Vietnam veterans' fathering babies with defects in the remaining 95 defect groups were similar. Similarly, there was little evidence of different risks for Vietnam veterans who had been assigned higher Agent Orange EOI scores or for Vietnam veterans who had stated during the interview that they believed they had been exposed.

It was determined that, for most defect groups, Vietnam veterans' risks were neither higher nor lower than those of other fathers. In any large study in which multiple statistical tests are done, some exceptions are expected. Some of the study's exceptions are noted below. The estimated risks for fathering babies with spina bifida (imperfectly formed spinal cord) were higher for Vietnam veteran fathers who received higher EOI scores. Vietnam veterans who had higher scores had higher estimated risks for fathering babies with cleft lip with or without cleft palate. Vietnam veterans, in general, had a lower risk for fathering babies with cardiovascular defects classified as "complex" defects (two or more cardiovascular defects). Vietnam veterans who stated they had contracted malaria while in Vietnam had a higher estimated risk for fathering babies born with hypospadias. (Hypospadias is a defect in which the urethra opens on the under side of the penis or into the vagina.)

No associations between risks of defects and use of malaria chemoprophylaxis were found.

Editorial Note: The most important conclusion to be drawn from this study is that the data collected contain no evidence to indicate that Vietnam veterans have had a greater risk than other men for fathering babies with defects when all types of serious structural birth defects are combined. This study cannot prove that some factor associated with service in Vietnam was or was not associated with he occurrence of rare types of defects, defects in the babies of selected individuals, or defects in the babies of small groups of veterans. The conclusion, however, that Vietnam veterans in general have not fathered, at higher rates than other men, babies with defects when all types of birth defects are combined is based on relatively strong evidence.

All parents are at some risk of having a baby born with birth defects. Because this risk is always there, it is called a "background risk". All men, whether Vietnam veterans or not, who father babies, have the same background risk about two or three chances out of 100 that their babies will have serious structural birth defects.

A summary report of this study has recently been published (1), and a more comprehensive report is available from CDC. Copies of these reports can be obtained from CDC's Chronic Diseases Division, Center for Environmental Health.

1. Erickson JD, Mulinare J, McClain PW, et al. Vietnam veterans' risks for fathering babies with birth defects. JAMA 1984:252;903-12.

On August 6, 1984, the Mississippi State Department of Health was informed of the death of an 11-year-old girl from Tunica County, Mississippi, and the hospitalization of her six siblings. The initial clinical diagnosis for the seven children was organophosphate poisoning. Neither the children's mother nor her live-in male companion was ill. Following is a summary of the State Department of Health's investigation.

On August 2, five of the seven children had visited a local physician complaining of abdominal pain of 2 days' duration. One child also had fever and diarrhea. The physician diagnosed viral gastroenteritis and suggested fluids and rest.

Later that day, all seven children were presented to a Memphis, Tennessee, hospital with signs and symptoms of organophosphate poisoning. Two were in respiratory arrest, and the other five had various degrees of lethargy, increased salivation, increased respiratory secretions, and pinpoint pupils. All the children had depressed serum and erythrocyte cholinesterase levels. One child could not be resuscitated and died. Preliminary autopsy findings were consistent with organophosphate poisoning and suggested ingestion as a primary route of exposure. A second child died August 9, and the other five children recovered and were discharged.

The male live-in companion reported having sprayed the inside of the house July 26 with a solution of insecticide in an attempt to control spiders. He had obtained a nearly empty insecticide container from the farm where he worked and had added water to it. Therefore, contamination of the drinking water was considered a strong possibility for exposure.

The sprayer solution contained the organophosphate insecticide methyl parathion in a concentration nearly three times that used for outdoor agricultural spraying. The drinking water in the house contained methyl parathion in a concentration above the suggested no adverse response level (SNARL); water from the well was negative for methyl parathion. The air inside the house contained over 100 times the concentration of methyl parathion measured in the air in the same locality during the spraying season; the air on the porch contained only one-seventh the amount found inside.

The 8-day delay between the reported spraying and the manifestation of classic symptoms of organophosphate poisoning is not explained. Efforts are under way to decontaminate the house and to reemphasize to the public the danger of organophosphate insecticides used inappropriately.

In November 1981, complaints of skin and respiratory irritation were reported to the National Institute for Occupational Safety and Health (NIOSH) by members of the housekeeping staff, which cleaned and disinfected patients' rooms at a community hospital in Oregon. The cleaning solutions the workers used contained a variety of irritating and toxic chemicals, including phenol, carbitol, ammonia, alcohols, detergents, waxes, and scrubbing compounds. Phenol was the principal ingredient of a germicidal solution applied to all objects and floors, when cleaning patients' rooms.

The 23 housekeeping employees reported the following symptoms with significantly greater frequency than did the employees not engaged in housekeeping: cough, history of producing phlegm, itching of the external ear, sinus congestion and light-headedness while at work. Four housekeeping employees had severe dermatitis of the hands and feet, and another four reported past histories of dermatitis. The onset of dermatitis for each of these patients was associated with a history of exposure of the skin to cleaning agents and disinfectants while at work. Changes in work practices were recommended to reduce skin exposures and associated dermatitis, including use of protective gloves and changes in application procedures (e.g., application of the germicide with a cloth rather than by spray bottle).

Editorial Note: Workers in hospitals are exposed to a wide variety of chemicals known to be hazardous, including waste anesthetic gases, ethylene oxide, and formaldehyde. In this investigation, NIOSH found dermatitis, as well as an increased incidence of symptoms of respiratory irritation, among housekeeping workers in a hospital. Workers were exposed to cleaning compounds containing phenol and were excreting phenol in their urine. Phenol has previously been shown to cause contact dermatitis following repeated exposure. Relatively simple precautions, such as work practices that limit the dispersal of solvents in the air and wearing personal protective gear, appear effective in reducing the hazard, by reducing contact of solvents with the skin.

Lead-containing folk remedies have previously been reported as the cause of lead poisoning in Mexican-Hispanic and Hmong children. A recent report of an infant death from lead- containing folk remedies in an Asian Indian family raises concerns that lead and other toxic substances may also be present in folk medicines from other parts of the world.

Following the death of a 9-month old infant, parents reported that they had regularly given folk medicine from India to their baby since he was two months old. Samples of three folk medicines were provided by the parents for analysis. All three contained lead. The highest concentration was in "ghasard" (16,000 ppm), a brown powder given daily as a tonic.

Those who work directly with people should be especially sensitive to the cultural beliefs and practices of ethnic groups. In their native countries they commonly use traditional foods and remedies, and they obtain folk remedies and advice from friends and relatives. Parents often give folk remedies to their infants and children to help them grow or to treat them for minor illnesses. In many instances the practices are harmless; however, there are reports that show that some folk remedies are harmful. Therefore, while undue anxiety should be avoided, health providers and educators working with a variety of ethnic groups need to be alert to potential concerns.

The following table provides a brief description of three Asian Indian folk remedies and the lead content of the products:

Name	Description	Lead Content (parts per million)
Ghasard	Brown powder given as a daily tonic.	16,000
Bala Goli	Round, flat, black bean-shaped. Dissolved in water it is used as a daily tonic or for stomach ache.	25
Kandu	Red powder used to treat stomach ache.	6.7

In the United States, the common use of vitamin and other nutrient supplements can be considered another kind of "folk remedy". They, too, are often given to children and other family members because of advice from relatives, friends, and from friendly advertisers and talk show participants on mass media. Misused, they too carry considerable risks.

REFERENCE: Centers for Disease Control. Lead poisoning- associated death from Asian Indian folk remedies-Florida. Morbidity and Mortality Weekly Reports 33:638, 1984.

A recent publication in the New England Journal of Medicine has reignited the controversy about the use of antibiotics in animal feed. While this is not strictly a toxicological question, it is one of deep concern for many of us involved in animal production. The following letter was published in the November 1984 issue of news from CAST, Volume 11, No. 6. It was sent to the Minority Counsel for the House Committee on Agriculture and addresses some key points that need to be kept in mind when evaluating the practice of antibiotic use as feed additives. Due to the length of the letter, I have included only portions of it which I think are the most important. If you wish a complete copy of the letter, please write to me and we will send one. A copy of the CAST report 88, Antibiotics in Animal Feeds can be obtained for $4.50 by writing CAST, 250 Memorial Union, Ames, Iowa 50011.

Dear Mr. Hogan:
Penicillin and tetracycline are two of the cheaper and more valuable antibiotics for both humans and food animals. Use of these antibiotics, like all others, results in development of strains of bacteria resistant to them. In theory, the development of resistance in pathogenic (disease causing) bacteria in humans as a consequence of use of antibiotics in production of food animals may arise in either or both of two ways: (1) By transfer of the resistant pathogens to humans from the animals. (2) By transfer in humans of suitable resistance elements (called R plasmids) from bacteria derived from the animals to originally nonresistant pathogens residing in humans. Regardless of the mechanism, the development of antibiotic- resistant bacteria in humans as a result of the production of resistance in bacteria in food animals from use of penicillin and tetracycline in animal production must be regarded as an undesirable side effect of such use of these antibiotics.

In the recent study by the Centers for Disease Control on an outbreak of salmonellosis in two midwestern states, the evidence pointed to hamburger from a beef herd in South Dakota as the source of the antibiotic-resistant Salmonella that caused the human sicknesses. But the beef herd was gone, and the hamburger was gone. The closest the CDC investigators were able to come to verifying that the hamburger was the source of the Salmonella was to find an R plasmid with the characteristic "fingerprint" in a Salmonella strain isolated from a dairy calf that had died on a farm adjacent to the one on which the beef herd had been fed.

Some supporters of the proposed FDA ban on the use of subtherapeutic levels of penicillin and tetracycline in animal feeds hailed the results of the CDC study as a clear link (a "smoking gun" in the words of one, and "The clarion is strong and clear" in the words of another) between antibiotic use in food animal production and antibiotic-resistant diseases in humans. Some opponents, on the other hand, pointed to the absence of the critical evidence and other flaws in the CDC investigation.

The imprecise wording of the statute appears to be an important part of the problem of decision-making. If taken literally, the Federal Food, Drug, and Cosmetic Act as Amended January 1980 in effect calls upon FDA to ban penicillin and tetracycline for animal feed additive use and for human use if these drugs are not "safe" for the intended purposes. The definition given for "safe" is simply that it "has reference to the health of man or animal". This language is largely meaningless, which makes its interpretation subject to endless argument.

As an example of the problems caused by the imprecise language of the statute, the practice of dosing humans with penicillin and tetracycline is far less safe for humans than the practice of feeding these antibiotics to animals. According to the letter of the law, therefore, FDA is obligated to take the irrational action of banning the use of penicillin and tetracycline in human medicine.

In our view, the potential for transfer of antibiotic resistance from bacteria in food animals to bacteria in humans is not a new development. It has existed from the day the practice of administering antibiotics to food animals was started. Farm people feed and handle food animals, and clean their quarters. Is there any doubt that these people come into contact with the bacteria the animals harbor, that they bring these bacteria into their houses, and that they thus expose all members of their households to these bacteria -- resistant and nonresistant, pathogenic and nonpathogenic? We think not. The risk for nonfarm people is more remote, but it still exists. How should the statutory "safe" be interpreted in the light of this situation?

An article by CDC investigators published in a recent issue of "Science" reported that 38 outbreaks of Salmonella infections with identified sources were investigated by the CDC from 1971 through 1983. Foods from animals were incriminated as the source of 11 of 16 outbreaks of antibiotic-resistant infections and 6 of 13 outbreaks of antibiotic-sensitive infections. The information from investigations like these can be quantified in such terms as numbers of persons hospitalized, numbers of work hours lost by these persons, and numbers of deaths. Not taken into account in studies of this kind is the probable decrease in Salmonella infections in humans associated with the decrease in such infections in food animals that receive antibiotics.

Some of the benefits to society from use of subtherapeutic levels of antibiotics in animal feeds can be quantified in terms of dollars, as was done in CAST Report No. 88. Human health effects related to consumption of greater quantities of animal products as a result of lower prices would be more difficult to quantify. The same would be true of the probable decrease in Salmonella infections in persons resulting from the decrease in Salmonella infections in food animals receiving antibiotics.

A few other points need to be made as an aid to developing a rational view of the antibiotic issue. One of these is that Salmonella infections are an ever-present risk. They may be derived from various foods, especially those of animal origin (whether antibiotics are used or not), but also from human-to- human contact and in other ways. It is a tribute to our food sanitation system that outbreaks do not occur more frequently than they do. For example, although hamburger was the suspected cause of the recent outbreak of salmonellosis reported by the CDC, the annual consumption of approximately 4 billion pounds of hamburger in the United States makes it evident that even hamburger is a low-risk product.

A second significant point is that Salmonella infections from food can be avoided by suitable cooking. Some of the women who contracted salmonellosis in the recent episode investigated by CDC admitted they might have tasted the raw hamburger they were preparing. Very likely they would not have become ill had they eaten only the well cooked product.

A third significant point is that the risk of antibiotic- resistant Salmonella infections in humans probably was increased by the use of antibiotics in animal feeds when the practice was started because at that time the numbers of animals receiving antibiotics were increasing rapidly. But the selection for resistant strains of bacteria within a given animal begins as soon as antibiotics reach these bacteria in concentrations great enough to be effective. With antibiotic use in animals stabilized for many years, there is reason to doubt that the contribution of feed use to the general level of antibiotic resistance in Salmonella is increasing, as sometimes is alleged. The latest information indicates that the antibiotic resistance level in gram-negative enterobacteria (a large group that includes Salmonella) in the United States has remained stable for at least the 12 years covered by the investigation.

A fourth significant point is that if the risk of illness from transfer of antibiotic-resistant Salmonella from domestic animals to humans is great, one should have noticed excessive sickness and death among people who work with food animals receiving antibiotics. The limited epidemiological information available does not support this supposition.

We hope these few points will help to place in reasoned perspective the issue of use of subtherapeutic levels of penicillin and tetracycline in animal feeds. Please let us know if we may be of further assistance.

Virgil W. Hays, Chairman
Department of Animal Sciences
University of Kentucky, and
Chairman, CAST Task Force on
Antibiotics in Animal Feeds

Charles A. Black
Executive Vice President
Council for Agricultural
Science and Technology

I hope this rather lengthy and long overdue newsletter will contain some information that will help to broaden the perspective of the reader.