UNIVERSITY OF CALIFORNIA DAVIS
ENVIRONMENTAL TOXICOLOGY NEWSLETTER
Vol 14 No 1 Feb 1994
"Published occasionally at irregular intervals"
In This Issue
- Pesticide Regulation in CA
- Organochlorine/Breast Cancer Link
- Jin Bu Huan Toxicity in Adults
- Molecular and Cellular Approaches to Risk Assessment
- "Circle of Poison" Not a Problem
- Behavioral Risk Factor Surveillance, 1991
- EPA's Tri-City Soil Lead Abatement Program
- Water Deserves More Respect
- Coca-Cola to the Rescue
- Personal Transportation: Cars
- Cocaine Acts as Natural Insecticide
- Organic Standards Board
- Selenium Supplementation
- Legal Restrictions on Compounding Drugs
- FDA Updates Vomitoxin Levels
- Effects of Animal Rights Violence
- Diagnosis of Common Silage Problems
This issue marks the beginning of the fourteenth year of publication for the Environmental Toxicology Newsletter. As usual, it contains some information that is peripheral to the field of toxicology, however, such information helps to keep chemical related issues in perspective. As always, we welcome suggestions for improvement of content and format. For anyone who is interested, we will provide electronic copies of articles for the entire issue. Within the next year, all past and future issues will be available on the Almanac system at Oregon State University as part of a cooperative USDA/ES program. Directions for use of this system will be included in a future (as yet unscheduled) issue.
PESTICIDE REGULATION IN CALIFORNIA
Michael W. Stimmann, Statewide Pesticide Coordinator
Damaging pests have been a problem since the beginning of agriculture. Weeds, insects, nematode worms and plant diseases have always damaged seeds, seedlings, mature crops and stored products. Throughout the history of agriculture, rodents andbirds have attacked crops and stored products while predators hav harassed and killed livestock. Pest management has always demanded a significant amount of a farmer's thought, time and effort. At times pests have devastated agricultural production and caused famines which starved millions of people. During the past half century scientific advances have given us new and powerful pest management tools. The most important of these tools are the synthetic organic chemical pesticides. To protect their crops, most growers, even those raising "organic" crops, find it necessary to use some pesticides from time to time. Pesticides have added to agricultural productivity, but they have also created serious new environmental and health problems for farmers and for all of society.
It is a scientific fact that every pesticide is toxic. All pesticides can injure or kill because chemical toxicity always depends upon the nature of the chemical, the dosage and the route of exposure.
Recognizing that pesticides are an agricultural necessity, state and federal governments began regulating pesticide production and use nearly a century ago. Building upon its pioneering efforts, California now has the most stringent pesticide regulatory program in the nation. Under California's rules, every farmer is required to know, understand and follow the laws and regulations when using agricultural pesticides.
Some Important Terms
Pests and pesticides are terms we use in our everyday conversations. Frequently these terms are used imprecisely, and confusion results. For example, poorly informed news reporters often write of pesticides and herbicides. This imprecise usage has led to the incorrect, but widely held belief that the term "pesticide" is equal to the term insecticide.
Two important definitions are:
Pests: Organisms which attack or otherwise adversely affect our crops, bodies, homes, pets, and livestock, or which compete with or attack our plants. Examples are some species of insects, weeds, nematode worms, fungi, snails, slugs, rats, mice and plant diseases. By this definition any unwanted plant, animal or microscopic organism can be considered to be a pest.
Pesticides: Substances or mixtures of substances intended for controlling any form of life declared to be a pest. Included among the pesticides are insecticides, herbicides, defoliants, fungicide , nematocides, and rodenticides. The definition of a pesticide is not limited to any particular kind of chemical or pest. By this definition even a common substance like water or table salt can be a pesticide if the user intends to use it to control a pest.
California's dense population centers often abut our intensive agriculture which has a high rate of pesticide usage. These conditions create a unique and potentially contentious set of pesticide-related problems. The federal law recognizes our unique conditions and allows California to regulate pesticide usage within its own borders.
Pesticide regulation in California is a three layered system: the federal and state governments adopt laws, regulations and policies, the state runs its pesticide regulatory program, and the counties develop their own policies and regulations and enforce the state program.
Pesticide Registration and Labels
Before a chemical may be used as a pesticide in the United States, it must be registered by the United States Environmental Protection Agency (EPA) under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA).
The foundation of pesticide registration is the label. A US EPA approved label signifies to the user that the pesticide is registered for use in the United States.
The pesticide label is a legally binding document. The information and instructions on the label are based on extensive scientific research. Information gathered through this research has been carefully crafted into the label which you must follow if you are to use the pesticide safely and effectively. If you fail to obey label instructions, you are violating the Federal law and you may be subject to severe legal penalties.
In addition to the federal regulation, any pesticide sold or used in the State must be registered by the California Department of Pesticide Regulation (DPR). Not all federally registered pesticides can be used in California because not all have been registered in California. The DPR reports that over time about 1,000 companies have registered more than 10,000 labels for pesticide products containing about 400 specific active chemicals in California. These pesticides may be used on over 200 food and fiber crops grown in California and 300 non-crop targets to control some 5,000 recognized species of pests.
Under the State Code, the California Environmental Protection Agency, Department of Pesticide Regulation has primary responsibility for implementing pesticide regulation; DPR operates in cooperation with the County Agricultural Commissioners (CAC) who have the responsibility of enforcing the program in their counties.
County Agricultural Commissioners actively enforce the pesticide laws and regulations and are alert for pesticide label violations. Each year hundreds of farmers are cited and fined for pesticide violations, so it is in your best interest to be very careful about following the label.
Pesticides for Minor crops
Most companies manufacturing and registering pesticides are major chemical producers who focus their efforts on the crops and pests most likely to result in maximum chemical sales. As a result, many pesticides are registered for major crops such as small grains, corn, soybeans, cotton and cattle. Unfortunately for the small farmer the pesticide industry generally cannot economically justify the high cost of registering pesticides on the minor crops which constitute most crop production in California. From the pesticide manufacturer's perspective, even crops like almonds, tomatoes, lettuce, tree fruits, grapes and citrus are minor crops! As a consequence it is often difficult to find effective pesticides registered for use on these crops.
To remedy this deficiency the Federal government has established a program to assist farmers in obtaining pesticide registrations on minor crops. This program is called Inter-Regional Project Number 4, or IR-4. The IR-4 program is administered by the University of California, Davis, and under certain circumstances IR-4 can assist farmers with pesticide registration problems. As with all such programs however, the process is complex and time consuming.
All pesticides registered for use in the United States are classified by US EPA as being either for general or restricted use. General use pesticides are available to anyone. These are the pesticides sold in supermarkets and hardware stores. General use pesticides present minimal risk to the user or the environment when label directions are followed. Permits are not required, but all agricultural uses of general use pesticides must be reported to the CAC.
Restricted use pesticides More hazardous pesticides are not available to the general public. They are highly regulated because they present health or environmental hazards even whenused according to the label instructions. Restricted use pesticides are available only to persons holding a Pesticide Use Permit. Anyone possessing or using a restricted use pesticide must obtain a permit from the CAC. Restricted use permits may include special conditions and restrictions beyond those on the pesticide label. For example, the CAC will evaluate the users knowledge of application techniques, safety and environmental protection. In addition the CAC will consider potential environmental impacts that can result from the application including groundwater hazards, wildlife hazards and the potential impact on people living nearby. If you use restricted pesticides, the State will require you to demonstrate your competency by testing your knowledge of problems and situations appropriate to your particular need. You must pass the state's examination to be granted a pesticide use permit in California.
Immediately before a restricted use pesticide is applied, a Notice of Intent to make the application must be given to the CAC. Following the application a Pesticide Use Report must be filed with the CAC.
To protect employees, all workers who are going to use pesticides must receive training from their supervisor. The training must be given and completed prior to beginning work with any pesticide. The farmer must keep a written record of the date, type, content and completion of the training. These records must be made available to the CAC upon request.
California has a very large and effective pesticide enforcement program with hundreds of trained inspectors. The County Agricultural Com-missioners or their staff inspect many pesticide applications. The inspectors are looking for compliance with pesticide label instructions, proper application techniques and equipment, personal safety equipment, applicator worker training, proper permits and compliance with environmental regulations.
Worker safety is of special importance to the California pesticide regulatory program. California has a history of frequent pesticide induced farm worker illnesses. Because of this we have developed the nation's most extensive mandatory reporting program for pesticide related illnesses. Under our program, physicians are required to report any pesticide related illnesses they diagnose. Following a physician's first report of pesticide related illness, the Department of Pesticide Regulation investigates to determine if pesticides caused the illness, if there was a violation, and if changes in pesticide use patterns or permit conditions can reduce or eliminate similar illnesses in the future.
Many pesticides are hazardous in the environment. Some pesticides can cause damage to nearby crops, other plants, wildlife, ground and surface waters and even to human neighbors. Preventing environmental damage is an important goal of the California pesticide regulatory program, and it must be a major goal of the small farmer as well.
The environmental behavior of most pesticides registered for use today is fairly well understood, and if label instructions are followed exactly, adverse environmental impacts will be minimized. As with any chemical product however, the less that gets into the environment the less there is to cause disruptions. As a result, all farmers are encouraged to review their pest management programs and to adhere to the principles of Integrated Pest Management whenever an IPM program is available.
As a pesticide user, you will want additional information on safe and effective pesticide use. Good sources of information are your County Agricultural Commissioner, your local University of California Farm Advisor, pesticide companies, pesticide dealers, licensed Pest Control Advisers and Certified Pesticide Applicators. Each has special knowledge to bring to your pesticide related problems. Where appropriate, use these resources to maintain your crop, your health and that of your employees, neighbors and customers. In the long run, safe and efficacious pesticide use helps us all preserve a healthy and prosperous agricultural community in California.
ORGANOCHLORINE/BREAST CANCER LINK SEEN; PHASE-OUT URGED
Citing evidence of a link between increased organochlorine exposure and increased incidence of breast cancer, a Greenpeace report released Oct. 15, 1993 called for a phase-out of chlorine and organochlorines. The report noted that for organochlorines that bioaccumulate -- including dioxin, PCBs (polychlorinated biphenyls), hexa-chlorobenzene, and some pesticides and other by- products -- the greatest exposures are through food.
"International correlations of fat intake with breast cancer rates do not necessarily indicate a causal relationship," Greenpeace said, noting that increased fat consumption is "almost always associated with the degree of industrialization and other changes that go with it, such as chemical and radioactive pollution and socioeconomic factors."
"No studies of dietary fat and breast cancer have considered the effect of chemical contaminants in the fat," the report said, noting: "Many persistent pollutants that cause or promote cancer --such as the chlorinated pesticides, PCBs and dioxins -- concentrate in fats. Fish, meat and dairy products account for as much as 98% of the human population's total exposure to these chemicals."
Vinyl chloride and vinylidene chloride, the report noted, "can leach out of containers and wraps into food and beverages."
Organochlorines can effect endocrine changes in people and wildlife, leading to reproductive and developmental impairment at current exposure levels, Greenpeace pointed out, suggesting that the levels may also be high enough to contribute to breast cancer. A number of organochlorines have been linked to mammary cancers or tumors in experimental animals. Suggesting that organochlorines are hormonally active environmental pollutants (xeno-estrogens), the report noted that other major sources of external estrogens are estrogens in milk and beef, including those from livestock feed additives.
Changes in breast cancer incidence rates, Greenpeace concluded, "appear to be associated with factors related to industrialization. Rising rates are most likely due to changes not in a single factor but have been caused by many exposures that influence both genetic and hormonal contributions to breast cancer. Reproductive and dietary risk factors account for only a very limited portion of total breast cancer incidence, and changes in these factors do not seem to fully explain rising rates of the disease, either. Exposure to radiation and chemicals that cause genetic mutations and hormonal alterations have increased rapidly in this century and may play an important role in the breast cancer epidemic."
Acknowledging that studies cited in the report do not prove, beyond a doubt, a cause-effect link between individual chemicals and the disease, Greenpeace said, "such a degree of proof will never be found, because of the complex reality of global chemical contamination and the limited tools available to toxicologists and epidemiologists."
The group called for a "new standard of proof," explaining: "The cardinal principle of public health practice is disease prevention. Requiring that cause-effect relationships be proven before taking action violates this principle. There is no scientific or ethical reason to presume chemicals harmless until they are proven otherwise. Such an approach allows action only after there has been irreversible harm to health and the environment. In public health and environmental policy, the pre- cautionary principle should be the framework for evaluating scientific information and for taking action."
This principle, the group explained, "places the burden of proof on those who would cause pollution rather than on those who would prevent it." It "requires that we err on the side of caution," and avoid the use of discharge of chemicals that may cause harm.
Calling for a phase-out of organochlorines, the report said alternatives are available for all major uses of chlorine. PVC plastic can be replaced with wood, metal, ceramic, paper products and chlorine-free plastics, the group said; chlorine bleaching of paper can be replaced with off-white paper or bleaching processes based on oxygen, ozone, hydrogen peroxide, enzymes, and/or metallic compounds; and chlorinated pesticides can be replaced with "organic" farming methods.
Governments, the group cautioned, should prohibit the substitution of other chemicals that produce persistent toxic substances, especially other halogens and organohalogens such as bromine or fluorine compounds, for chlorine and organochlorines.
REF: Food Chemical News, Oct. 18, 1993.
JIN BU HUAN TOXICITY IN ADULTS --Los Angeles, 1993
Jin Bu Huan (JBH) is a traditional Chinese herbal product used as a sedative and analgesic. During 1993, public health and health- care providers in Colorado reported three children with unintentional overdoses of JBH that caused central nervous system and respiratory depression with rapid onset of life-threatening bradycardia. Subsequently, the first cases of acute hepatitis attributed to use of JBH were diagnosed in three women in Los Angeles during July and August 1993. All three patients had purchased JBH at the same health-food store.
In July, a 66-year-old woman sought care from her physician for fever, nausea, and fatigue of 2-3 days' duration. Liver test results were elevated. During May-July, she had used two JBH tablets at night, two to three times per week, for back pain and insomnia. In mid-July, she reportedly discontinued use of JBH because of her illness. By mid-August, her liver test results had improved to slightly above normal. The patient resumed use of JBH (two tablets each night) for 1 week and again had elevated test results. She discontinued use of JBH a second time in early September. Three weeks later, she was asymptomatic, and liver enzymes had returned to normal.
In August, a 24-year-old woman sought care from her physician for fever, nausea, vomiting, fatigue, and pruritus (severe itching) of 2-3 days' duration; she had jaundice, excoriations (abrasions) of her limbs and tender hepatomegaly (liver enlargement). She was hospitalized for 5 days. During June and July, she had used four JBH tablets at night, four times per week, for insomnia. She noted onset of jaundice in mid-July but continued use of JBH for 2 additional weeks. Nine weeks after discontinuing use of JBH, the patient was asymptomatic, and liver enzymes had returned to normal.
In August, a 45-year-old woman sought care from her physician for nausea, anorexia, fatigue, pruritus, and abdominal pain of 2-3 days' duration. Liver test results were elevated. During May- August, she had used four JBH tablets at night, three to four times per week for insomnia. During January-August, she had intermittently used another Chinese herbal product, Ma Huang (active ingredients include ephedrine and pseudoephedrine). She noticed onset of jaundice in mid-September. In late September, she reportedly discontinued use of both herbal products because of her illness. During the next 2 weeks, her symptoms resolved, except for mild pruritus. Nine weeks after discontinuing use of JBH, the patient was asymptomatic, and her liver test results had improved.
The package insert for JBH tablets recommends use to treat pain and insomnia and indicates a composition of 70% starch and 30% levo-alkaloid from the plant Polygala chinensis. Tablets from patients 1 and 2 were analyzed; the tablets contained 36% levo- tetrahydropalmatine (L-THP), a chemical present in plants of the genera Stephania and Corydalis but not present in the genus Polygala. The remaining constituents were inert and no other plant materials or chemicals were identified. The Food and Drug Administration (FDA) is investigating this product.
Editorial Note: The ingredients identified in the JBH tablets from two of the three case-patients in this report were identical to those extracted from the JBH tablets retrieved from the previously reported cases of overdose in children. The findings in this report suggest that JBH (or one of its components) may be hepatotoxic; therefore, JBH should be avoided by persons with known liver disease.
The severity of the adverse health effects in these three cases underscores the potential health risks associated with use of herbal products. In North America, Chinese herbal products are sold as over-the-counter remedies for a variety of ailments. Although package inserts claim the safety of herbal products, previous reports have documented the risk of adverse health effects associated with use of these products.
Because the marketers of herbal products maintain that these products are dietary supplements rather than drugs, herbal products generally are not subject to standard testing for safety and efficacy. For the three cases in this report, the plant source and percentage of the active ingredient indicated on the JBH labels were incorrect. Consumers should be warned that the term "natural" on a label does not ensure product safety.
Reporting systems have not been available to collect data about adverse reactions to dietary supplements, including botanical products. However, FDA's newly implemented MEDWATCH program, which monitors reports of adverse reactions to FDA-regulated products, may enhance surveillance because it specifically requests reports of adverse reactions to dietary supplements.
REF: Morbidity and Mortality Weekly Report, 42(47), December 3, 1993.
WORKSHOP PARTICIPANTS DISCUSS MOLECULAR AND CELLULAR APPROACHES TO RISK ASSESSMENT
Citing information gaps between animal and human data sets and the relatively limited use of in vitro data in risk assessment, 40 representatives of government, industry and academia met to discuss the need for a new approach to the evaluation of human risk.
Workshop participants discussed the need for a four-cornered experimental approach to knowledge of the mechanism in which in vivo and in vitro animal studies are utilized, together with epidemiologic data and in vitro studies using human cells, in a "weight of evidence" model for the evaluation of human risk.
The course organizer stated that "the four-cornered approach is certainly not new, but given the current impetus to incorporate biologically relevant information into the risk assessment process, it is timely. Without the incorporation of human in vitro data into the risk characterization process, or the improved sensitivity of the methods of human epidemiology, biologically-based risk assessments will simply represent improved models for the interpretation of data generated by animal experimentation and not necessarily improved estimates of true risks to humans."
There was considerable discussion on the sex and species-specific nephrotoxicity of d-limonene (oil of orange), widely used as a flavor/fragrance. D-limonene is unequivocally a male rat carcinogen, according to NTP bioassay results. There have been a series of in vivo and in vitro studies which established the mechanism responsible for the compound's unique toxicity in male rats, hyaline droplet or a2u-globulin nephropathy. Toxicity is not seen in any sex or species, including humans, that does not synthesize a2u-globulin. This data has been incorporated by EPA into its risk assessment strategy.
REF: The Johns Hopkins Center for Alternatives to Animal Testing, 11(1), Fall 1993.
"CIRCLE OF POISIN" NOT A PROBLEM
FDA and USDA testing of imported food "showed few violations of residue tolerances involving unregistered exported pesticides on foods imported into the U.S.," GAO (General Accounting Office) noted in a report which, however, recommended consideration of a FIFRA (Federal Insecticide, Fungicide and Rodenticide Act) amendment to require "manufacturers of unregistered pesticides sold to foreign purchasers to provide EPA with information on export destinations, foreign registration, pesticide reference standards and test methods and require EPA to make this information available to FDA." The GAO report's recommendation to EPA was to work with industry to get the above information if there was no FIFRA amendment requiring it.
The report, "Pesticides: Limited Testing Finds Few Exported Unregistered Pesticide Violations on Imported Food," was filed with Sen. Leahy (D-Vt.), who had requested the examination of the so-called "circle of poison."
GAO looked at USDA and FDA results of testing imported food for violative residues of a target group of 27 pesticides not registered for food use in the U.S. between 1989-91. The report noted that FDA tested for 14 of the 27, finding "few residue violations." USDA also found few violations, the report said.
The report said, "From 1989 through 1991, FDA tested imported produce for 14 of the pesticides on our list. It tested more than 23,000 samples for each of 11 of the 14 pesticides, 18,000 samples of one pesticide, and over 1,000 samples for each of the last 2 pesticides. It found 88 violations involving four pesticides. One pesticide --monocrotophos, an insecticide used on various imported fruits and vegetables -- accounted for 69 of the 88 violations, a violation rate of 0.28% of samples taken. The three other pesticides (EPN, prothiophos and heptachlor) had violation rates at levels of less than 0.05% of the samples taken." FDA did not test for DBCP and ethylene dibromide, the report noted, because they are primarily used as fumigants and dissipate quickly.
USDA tested imported meat and poultry for chlordane, heptachlor and mirex, finding no violations among 7,200 samples, the GAO said. The department said that for the remaining 24 pesticides, testing was not done because Agriculture did not have specific health concern information on them.
REF: Kansas Pesticide Newsletter 16(12) Dec 10, 1993.
BEHAVIORAL RISK FACTOR SURVEILLANCE, 1991: MONITORING PROGRESS TOWARD THE NATION'S YEAR 2000 HEALTH OBJECTIVES
Definitions of Risk Factors and Medical Screening Practices
The proportion of adults >18 years of age who were overweight ranged from 17.8% in Colorado to 28.7% in Michigan (median = 23.4%). When compared with the total population, the median prevalence of overweight was higher among low-income women (30.3%) and black women (39.0%). Although the median for Hispanic women was lower (24.4%), the sample size was sufficient for analysis in only 10 states. The percentage of adults with self-reported high blood pressure who were overweight was high (median = 40.5% for women and 42.5% for men).
No Leisure-Time Physical Activity
The percentage of adults who did not engage in leisure-time physical activity varied nearly threefold, from 16.6% in Montana to 42.6% in Mississippi (median = 28.0%). In general, prevalences were lower in western states (Colorado, 18.0%; Oregon, 19.6%; and Washington, 20.6%). The median percentage among both low-income persons (37.3%) and adults >65 years of age (42.3%) was substantially higher than for the total adult population.
The percentage of adults >18 years of age who reported that they were cigarette smokers ranged from 14.3% in Utah to 30.2% in Kentucky (median = 23.0%). The median prevalence among adults who had a high school education or less was about five percentage points higher than the median among the total adult population. The percentage of current regular smokers who quit smoking at least 1 day in the past year ranged from 42.0% in Ohio to 60.9% in Michigan (median = 55.6%).
Only Utah reported a prevalence of smoking that met the year 2000 objective in the total adult population. No state reported a prevalence below the smoking objective for adults with a high school education or less or for women of reproductive age.
Safety Belt Use
The percentage of adults >18 years of age who reported that they always wore a safety belt while riding or driving in a car ranged from 22.8% in South Dakota to 87.8% in Hawaii (median = 58.2%).
The percentage of adults >18 years of age who had had a blood cholesterol screening test within the previous 5 years ranged from 56.2% in New Mexico to 71.3% in Connecticut (median = 63.7%). Prevalences were highest in four northeastern states and Florida: New Jersey (71.2%), Florida (71.1%), New Hampshire (70.2%), Rhode Island (69.6%), and Massachusetts (68.0%). The median percentage of adults who had had a blood cholesterol screening test within the previous 5 years (63.7%) was about 10 percentage points below the year 2000 objective (>75%). As of 1991, no state had reported a prevalence consistent with this objective.
Breast Cancer Screening
The percentage of women >40 years of age who had ever had both a mammogram and a clinical breast examination ranged from 55.5% in Louisiana to 83.1% in the District of Columbia (median = 69.7%). However, the median prevalences were lower for each of the population subgroups .
The percentage of women >50 years of age who had had a mammogram and a clinical breast examination within the previous 2 years was highest in the District of Columbia (82.8%) and lowest in Louisiana (45.6%) (median = 57.8%). The prevalence of screening was lowest among low-income women >50 years of age (median = 41.4%).
The median percentage of women >40 years of age who had ever had both a clinical breast examination and a mammogram (69.7%) was about 10 percentage points below the year 2000 objective (>80%). The District of Columbia (83.1%) and Washington (81.4%) met that objective in 1991. Many states reported prevalences above the year 2000 target percentage (>60%) for women >50 years of age who had had both examinations within the previous 2 years. Only the District of Columbia, however, reported prevalences higher than this objective for each population subgroup.
The percentage of women >18 years of age who had ever had a Pap smear was high in all states, ranging from 86.8% in New York to 95.3% in Colorado (median = 92.4%). The median prevalences for the special population subgroups were lower (range = 83.9%-85.8%). Washington and Oregon were the only states where at least 90% of all groups reported having had a Pap smear.
The median percentage of women >18 years of age who had ever had a Pap smear was <3 percentage points below the year 2000 objective of 95%. Colorado, Maine, Oregon, and Washington reported prevalences at least as high as this objective. With regard to special population subgroups, Washington reported a prevalence at least as high as the year 2000 objective for low- income women, Idaho for women who had less than a high school education, and Colorado for Hispanic women.
The percentage of women >18 years of age who had had a Pap smear within the past 2 years ranged from 73.7% in West Virginia to 87.5% in the District of Columbia (median = 79.7%). Median prevalences were lower for each of the special subgroups, particularly for women >70 years of age (55.7%). Fewer than half of women >70 years of age had had a Pap smear within the past 2 years in Georgia, Indiana, Kentucky, Louisiana, Massachusetts, New Hampshire, and Vermont.
The median percentage of women ages >18 years who had a Pap smear within the previous 2 years (79.7%) was about 5 percentage points below the year 2000 objective of >85%. The District of Columbia and Maryland reported prevalences at least as high as this objective. Only the District of Columbia reported a prevalence at least as high as the year 2000 objective for each special population subgroup.
REF: Morbidity and Mortality Weekly Report 42(SS-4) Aug 27, 1993.
EPA'S TRI-CITY SOIL LEAD ABATEMENT PROGRAM
The EPA has issued a draft report on the results of its Tri-City Urban Soil Lead Abatement Program, which studied the impact of soil, house dust, and paint abatement on children's blood lead levels. The program was conducted in areas of Boston, Baltimore, and Cincinnati known to have high levels of children's blood lead or environmental lead. The study took 5 years, including 3 years for sample collection and analysis, and $15 million in federal funding. The EPA predicted that a reduction of 1,000 ppm in soil lead would result in a blood lead reduction of 3 to 6 ug/dl.
A review of the study concludes that soil abatement is ineffective in reducing the blood lead levels of children living in the abated areas. After much statistical manipulation, the EPA has concluded that the reduction of soil lead, in the Boston study only, results in a reduction of 1 ug/dl for each 1000 ppm of soil lead reduction. The Cincinnati study (where there was very little soil in yards), and the Baltimore study concluded that "soil abatement has no effect on children's blood lead levels."
The report supports the use of blood lead measurements to evaluate exposure based on the following statement: because there is a relationship between blood lead and the onset of health effects of lead, it is convenient for this measure of blood lead to be used both as an indicator of exposure, and a measure of the potential health risk to the child.
One of the important concepts presented in the draft report is the seasonally adjusted correction factor for blood lead concentrations. The EPA states that blood lead concentrations typically vary by about 30% seasonally, and peak in the late summer. This correction appeared to be the same for all three studies, and was applied to the interpretation results. This concept weakens EPA's enforcement position that blood lead studies are simply a snapshot in time, and are not useful to estimate exposures. This new EPA information indicates that short-term variations in blood lead concentrations are consistent and can be used to estimate long-term exposure.
REF: Lead Bulletin, December 1993.
WATER DESERVES MORE RESPECT
Even though most of the planet is covered with water, very little of it can be used by humans. This most-taken-for-granted of all resources has produced some facts worth thinking about:
REF: Veterinary Medicine Newsletter (University of Florida) 2(6), Nov/Dec 1993.
COCA-COLA TO THE RESCUE
Patients who suffer from episodes of difficulty in swallowing due to benign stricture of the esophagus -- a complication of esophageal reflux -- usually arrive for treatment with a bolus, or piece of unmasticated food, trapped in the narrow esophagus. Management of this condition consists of endoscopy to remove the bolus, a biopsy of the stricture, and its dilation with balloon dilators. The bolus has a tendency to fragment during removal, requiring several endoscopies, an uncomfortable procedure for the patient.
Two British surgeons, N.D. Karanjia and M. Rees, have suggested that patients drink Coca-Cola or another effervescent beverage to break up the bolus before endoscopy. They report on bolus obstruction in 13 episodes, patients were given Coca-Cola the day before endoscopy and the next day the bolus had cleared. In seven episodes patients were given no special treatment before endoscopy. In all of these cases a bolus was present at endoscopy and had to be removed in pieces, necessitating repeated passes of the endoscope.
The surgeons speculate that fizzy drinks might produce disintegration in the bolus by penetrating it and releasing carbon dioxide gas within. Aerated liquids, if able to seep past the obstruction into the stomach, might produce eructations which would dislodge the bolus. Champagne, according to these gentlemen, might work equally well.
REF: Veterinary Medicine Newsletter (University of Florida), 2(6), Nov/Dec 1993.
PERSONAL TRANSPORTATION: CARS
Car Accidents: Nearly 47,000 people are killed each year on US roads and highways.
Pollution: From the removal of petroleum from the earth to the burning of gasoline in the car, the potential for environmental degradation of the air, land and water are evident. According to the National Research Council, roughly 3 million tons of petroleum enter the ocean each year. Only 8% of this comes from natural sources. Forty-five percent of the total comes from marine transportation; 37% from municipal and industrial wastes and runoff. In 1900, 21% of the discharge from marine transport stemmed from accidents. Tankers emptied the remaining 79% (450,000 tons) of the marine transport discharge oil total during routine operations.
Car owners currently discard about 20 million dead batteries and 250 million tires a year. Each battery contains approximately 18 pounds of lead.
About 60 percent of all the lead that ends up in landfills or incinerators comes from car batteries. Lead exposure may cause neurological damage, most notably in children and fetuses. At higher doses, lead can damage kidneys and degrade the immune system.
Refined petroleum emits a variety of atmospheric pollutants as it is burned in the engines of passenger transportation vehicles. A single individual in a gasoline-powered car emits over 54 pounds of pollutants and 1,120 pounds of carbon dioxide for every 1,000 passenger miles. On a per capita basis, the average Floridian travels almost 8,000 miles every year. A recent study by the University of California-Davis estimates that 25,000 people die each year from automobile air pollution. According to the World Resources Institute's report The Going Rate: What It Really Costs to Drive, the social costs of driving that are not paid by drivers add up to about $300 billion.
Don't Drag: On the highway, air conditioning is the energy efficient cooling choice. Open windows impede air flow over the car, increasing aerodynamic drag and fuel consumption.
Wash Water: Washing your car at home with a standard garden hose can use up to 140 gallons of water and almost 3,000 Btu of energy (to supply the water). Professional car washes use 10 to 40 gallons of water per car and many use recycling equipment that recycles wash water for reuse.
When you wash your car at home, the soapy runoff water often ends up in the city storm drains which carry it directly to rivers and other water sources. Waste water from a car wash facility is piped to an appropriate water treatment facility.
Disposing Tired Tires: Americans throw away 250 million tires each year. There's more than 58 million barrels of oil in these tires. Don't landfill them; used tires can be retread or blended with asphalt to make road coverings.
Oil and Water Don't Mix: It takes 50 gallons of crude oil to make one gallon of motor oil. About 240 million gallons of oil are dumped into lakes and rivers and onto the ground each year by people who change their own oil; that's equivalent to an oil spill the size of Exxon Valdez every two weeks.
Recycled oil can become fuel for ships and industrial boilers or new motor oil. To learn where you can recycle oil in your community, write to the Used Oil Coordinator, Mail Code OS 301, US EPA, 401 M Street SW, Washington, DC 20460.
Filters: Cleanable, reusable air filters and permanent (100-oil change) oil filters keep lots of filters out of the garbage.
REF: Veterinary Medicine Newsletter (University of Florida), 2(6), Nov/Dec 1993.
COCAINE ACTS AS NATURAL INSECTICIDE
Cocaine has been found to have surprising insecticidal effects at levels in which it occurs naturally in plants. Cocaine is obtained from the leaves of coca plants, but its natural function in plants has previously been unknown. Curious about another group's earlier observation that coca plants tend to be relatively pest free, James A. Nathanson and coworkers in the department of neurology at Massachusetts General Hospital in Boston decided to examine cocaine's effects on feeding in insects [Proc. Natl. Acad. Sci USA, 90 9645 (1993)]. Their experiments showed that insect larvae exposed to cocaine sprayed leaves display "marked behavioral abnormalities, including rearing, tremors, and walk-off activities." Their data indicate that cocaine's toxicity stems from its ability to block reuptake of octopamine, a key insect neurotransmitter and hormone that regulates movement, behavior, and metabolism. The researchers point out that cocaine's effects in humans -- which are caused by blockage of reuptake of the neurotransmitter dopamine -- are likely an unintended evolutionary side effect of its ability to block amine reuptake in insects.
REF: Kansas Pesticide Newsletter, 17(1), Jan 14, 1994.
ORGANIC STANDARDS BOARD
The Livestock Committee of the National Organic Standards Board (NOSB) has developed a recommendation on the use of synthetic antibiotics in organic livestock production, and is circulating it for public comments.
The full NOSB will vote on the recommendation in 1994. The policy as proposed follows AVMA's (American Veterinary Medical Association) recommendations on the use of antibiotics in organically produced livestock; namely, that once an antibiotic is used on organically produced livestock, that animal is no longer eligible for organic status. The text of the NOSB proposal follows:
The use or application of synthetic antibiotics in organically produced slaughter livestock that is labeled or sold as organically produced, is prohibited.
Should a synthetic antibiotic be administered for whatever reason, to otherwise organically produced livestock, that livestock and any products derived therefrom shall not be labeled or sold as organically produced.
The use or application of synthetic antibiotics in animals labeled or sold as organic breeder stock, the progeny of which is intended to be labeled or sold as organically produced, is restricted. Organic breeder stock may receive application of synthetic antibiotics in the event of a healthcare emergency. In such instance, the progeny may be sold or labeled as organically produced provided that the application to the breeder stock does not occur in the last third of gestation or while nursing the progeny, and the application is prescribed by a licensed veterinarian. The organic breeder stock, having received an application of synthetic antibiotics, is not disqualified from having its future progeny sold or labeled as organic.
Should a synthetic antibiotic be administered for whatever reason, to otherwise organically produced dairy stock, milk or milk products derived from that dairy stock may not be sold or labeled as organically produced for 12 months following the date of application or use.
One clarification that may be necessary to add is the issue of breeder stock that may later become slaughter stock. The policy should clearly state that if an animal is treated with antibiotics at any point in its life, it can never be labeled or sold as organically produced slaughter stock. This point may be particularly relevant for dairy cattle, which may be treated with antibiotics and continue to produce calves, and may even produce organic milk 12 months following treatment, but may never be offered for slaughter as organic beef.
AVMA may also recommend that the policy contain wording to assure that slaughter stock that have been treated with antibiotics are not marketed while they still have antibiotic residues in their system. AVMA may also wish to mention that failure to treat a sick animal, in order to maintain its organic status, should be grounds for disqualification of the entire production operation.
The livestock feed standard requires that all certified organically produced livestock be fed 100 percent certified organically produced feeds and feed supplements, and that pasture land upon which livestock are grazed or pastured shall be certified as organic. In the event of a feed availability emergency, producers may feed animals nonorganic feed for a limited time period determined by the certifying agent. Again, these strict standards are compatible with AVMA's assertion that organic livestock production practices be distinct from conventional production.
The proposal on livestock sources requires that livestock be purchased from organic sources, with limited exceptions. All stock must be raised under organic production methods from the time they are brought onto a certified organic farm. Livestock or livestock products that do not meet the organic standards are required to be diverted to the conventional market when sold. The recommendation also discourages producers from retaining nonorganic livestock in the organic farming operation.
REF: AVMA Washington Veterinary News, Dec 1993.
SELENIUM SUPPLEMENTATION RETURNS TO PRE-1987 LEVELS
In April 1987, FDA amended the Agency's selenium food additive regulation to increase the maximum selenium supplementation allowed in animal feeds. The Agency has now stayed those amendments, returning the maximum allowable selenium to the pre-1987 levels. Additionally, the requirement for analysis of each batch of selenium premix has been reinstated.
In 1987, amendments were published that permitted: (1) an increase from 0.1 to 0.3 ppm selenium in complete feeds for cattle, sheep, chickens, ducks, and swine; (2) an increase from 0.2 to 0.3 ppm for turkeys; (3) an increase in the limit feeding (feed supplements and salt-mineral mixtures) consumption rates for sheep and beef cattle to 0.7 and 3 milligrams per head per day, respectively; and (4) an increase in the selenium fortification levels for salt-mineral mixtures for sheep and cattle to 90 and 120 ppm, respectively. At the same time, the regulation was amended to eliminate the requirement for premix manufacturers to analyze each production batch of selenium premix and to include requirements for current good manufacturing practices (GMPs) for the manufacture of selenium premixes.
FDA has also announced that firms manufacturing selenium premixes will be required to assay those premixes. The Agency's Denver District Laboratory has developed a colormetric sodium selenite premix method which was recently validated using CVM's Method Trial procedures.
The 1987 amendments are stayed, effective September 13, 1993. In addition, the 1989 amendment that provided for the use of a controlled-release selenium bolus is also stayed effective September 13, 1993.
In 1989, the selenium food additive regulation was amended to provide for use of a controlled-release bolus for cattle, in accord with the maximum permitted use levels specified in the 1987 amendments. At the time of the bolus amendment, the EA (environmental assessment) prepared by the petitioner addressed only the environmental impact of the manufacture of the bolus, relying on the EA and FONSI (finding of no significant impact) for the 1987 amendments to address the potential environmental impacts due to the use of the increased level of selenium and its subsequent introduction into the environment through animal wastes. Thus, the selenium bolus amendment of 1989 is also affected by this action. To facilitate an orderly implementation of the stay and transition to the lower maximum supplementation levels, the Agency will exercise enforcement discretion for a period of one year. The Agency will not take regulatory action against feeds, feed supplements, salt-mineral mixtures, and premixes complying with the 1987 amendments during this period. Because the bolus provides selenium for a 120-day period, no regulatory action against the sale and/or use of the bolus will take place until 8 months after the effective date of the stay.
The September 13, 1993, Federal Register document detailed the environmental information needed. If the Agency determines that the progress is not adequate, FDA will take the action necessary to deny the petition and revoke the 1987 amendments. For that reason, information about all research endeavors, including protocols, contracts, and results should be submitted to the Dockets Management Branch, (HFA-305), Food and Drug Administration, Room 1-23, 12420 Parklawn Drive, Rockville, MD 20857, and identified with Docket Number 86F-0060.
REF: FDA Veterinarian, VIII(VI), Nov/Dec 1993.
LEGAL RESTRICTIONS ON COMPOUNDING DRUGS
The following information is taken from a presentation by Richard E. Geyer, Deputy of Surveillance and Compliance, at a symposium on compounding in veterinary medicine, held September 9-10, 1993.
The question implied by the title of this article is "Are there legal restrictions on compounding?" The answer, of course, is "yes."
Under the Federal Food, Drug, and Cosmetic Act, the sale of bulk drugs to veterinarians for their use in compounding is illegal. Note that the emphasis is on restriction of the sale of the bulk substances to veterinarians, not compounding per se. That statement is supported by uncontradicted court decisions.
The illegality of the sale of bulk drugs to veterinarians is established by the decisions of two United States circuit courts of appeals in the 1980s. One case involved an Illinois-based firm, Schuyler Laboratories, and the other a New Jersey Company, Algon Chemical Company. Both firms sold bulk drugs to veterinarians for their use in compounding. The government went to court in both instances to stop the sale of the bulk drugs.
The government's position was that the Act establishes that all drugs, including bulk drugs, are misbranded unless they bear adequate directions for use. The Act allows the Agency to exempt bulk drugs from that requirement because it makes little sense to require directions for use for substances that are not to be used in their present form. However, the exempting regulation (21 CFR 201.122) has a caveat. The exemption does not apply if the finished product is an unapproved new drug or new animal drug.
The courts upheld FDA's argument; they concluded that Congress did not intend to create an exception to the approval process for drugs that might be compounded by veterinarians. To do so would open up a potentially large alternative to the requirement that drugs be shown to be safe and effective. The finished products the veterinarians were making were not FDA-approved, but the firms argued that approval wasn't necessary because of a "practice of medicine" exception that covers such products. They pointed out that the Act exempts practitioners who compound from the requirement of registration and inspection. From this, they argued that Congress meant to allow veterinarians to compound without restriction.
The courts obviously could not accept this argument and at the same time maintain their position that the approval portion of the statute applies to drugs compounded by veterinarians. The courts concluded that the exemptions from registration and labeling referred to compounding only from drugs they could lawfully obtain, and, unless the compounded product meets an exception to the approval requirement, they could not legally obtain the bulk drugs to make those products.
The courts also gave attention to the fact that the firms did not establish that bulk drugs were really needed for compounding -- only that bulk drugs are preferred because they are cheaper and more convenient to use.
Although the cases focused on drugs for use in food animals, their holdings would apply equally to drugs for companion animals.
The Supreme Court was petitioned, but refused to consider the issue. Since the time of the Court of Appeals' decisions, more than 50 persons, including a number of veterinarians, have been prosecuted for importation and distribution of bulk drugs for use in compounding.
The courts concluded that veterinarians could compound from drugs they could legally obtain. Obviously, veterinarians can legally obtain approved, finished new animal drugs. Therefore, it would seem logical that veterinarians could compound without restriction from approved new animal drugs.
In examining this premise, one finds a major legal impediment. The Act states unequivocally that animal drugs cannot be used in a manner that is inconsistent with their approved labeling. The statute does not provide an exception for extralabel use by veterinarians. If we apply the reasoning of the courts in the bulk drug cases, it would be incorrect to read an exception for compounding as an exception to this statutory prohibition against extralabel use.
The courts in the Algon and Schuyler cases did acknowledge that FDA permitted compounding from approved drugs within the limits of its discretionary extralabel use policy. Because the extralabel use policy is an exercise of enforcement discretion, which permits a technically illegal act, the policy could be unilaterally withdrawn by FDA. Further, since the Compliance Policy Guide was written primarily for extralabel use without compounding, its terms do not clearly fit compounding situations.
The bulk drug cases involved drugs intended to be compounded by veterinarians. Conceptually, the same conclusions should apply to bulk drugs intended to be compounded by pharmacists. The regulation FDA successfully relied on, 21 CFR 201.122, applies to compounded drugs regardless of who does the compounding. Thus, compounding of new animal drugs by pharmacists, like such compounding by veterinarians, would have to be done through an exercise of enforcement discretion by FDA.
REF: FDA Veterinarian, VIII(VI), Nov/Dec, 1993.
FDA UPDATES VOMITOXIN ADVISORY LEVELS
FDA has received numerous reports indicating that a significant portion of the 1993 hard red spring wheat crop from States in the upper midwest may contain high levels of deoxynivalenol (DON), commonly called vomitoxin. DON is produced by several molds of the genus Fusarium, especially F. graminearum, which causes pink scab disease in wheat. It is not possible to completely avoid the presence of DON in wheat. DON is sometimes found in wheat grown under normal weather conditions, however, the fungus thrives in the cool, wet conditions that occurred in the midwest in the spring and summer of 1993. When DON occurs in wheat, the levels are reduced by the processing of wheat into wheat products like flour, but processing does not totally eliminate DON.
Based on the available data and information, FDA can now state with more confidence, the levels of DON in wheat and wheat-derived products that would not appear to present a public health hazard. Thus, FDA is updating its advisory levels for DON in wheat and wheat-derived products for human food and in grains and grain byproducts for animal feed. This advisory is responsive to circumstances resulting from the abnormally wet conditions experienced in the midwest this year.
The following advisory levels are supported by the scientific literature, but may change as further evidence becomes available. Based on the findings in the scientific literature, the FDA believes that these levels should not produce any adverse animal or public health effects.
REF: FDA Veterinarian, VIII(VI), Nov/Dec 1993.
JUSTICE DEPARTMENT'S REPORT OF THE EFFECTS OF ANIMAL RIGHTS VIOLENCE ON TARGETED INDUSTRIES
We have a copy of this "Report to Congress on the Extent and Effects of Domestic and International Terrorism on Animal Enterprises" from the Justice Department. If anyone would like a copy of this document, please contact our office.
Diagnosis of Common Silage Problems
Specific Symptoms and Possible Cause(s)
REF: Penn State Veterinary News, November 1993
Arthur L. Craigmill, Ph.D.
Environmental Toxicology - University of California
Davis, CA 95616-8588
(530)752-2936 FAX: 752-0903
Michael W. Stimmann, Ph.D.
(530)752-7011 FAX: 752-0903