UNIVERSITY OF CALIFORNIA
EXTENSION TOXICOLOGY NEWSLETTER
Vol. 9 No. 5 December 1989
" FAREWELL TO THE 80's "
Table of Contents Page No.
II. Inadvertent Contamination of Row Crops from Pesticides in Fog
III. Lead Poisoning in Bridge Demolition Workers -- Massachusetts
IV. Radon Exposure Assessment -- Connecticut
V. Update: Eosinophilia-Myalgia Syndrome Associated with Ingestion of L-Tryptophan -- United States
VI. Crystallized Chemicals Pose Explosion Hazard
VII. Ethylenediamine Dihydroiodide (EDDI)
VIII. The Regulation of Food Additives in Animal Feeds
IX. Extra-Label Use of Drugs
X. New Private Sector Support for 4-H Veterinary Science Awards Program
This issue of the Environmental Toxicology Newsletter closes the door on 1989 and marks the end of the decade. Carl has contributed an article about the recent finding that fog has been identified as a mechanism for pesticide movement in the environment resulting in residues on crops that were never actually sprayed. Allison has contributed an article that should raise the hair on the necks of many people, just as it did to her. The other articles have been taken from a variety of sources. The article on the regulation of food additives in animals feeds should be of interest to many people who are now involved with the food safety issue.
To close out the year I would like to publicly thank all of the people who have contributed to the production of this newsletter including the folks in Ag Publications in Oakland who have done an outstanding job of getting the newsletter published very quickly. A special note of thanks to Sandy Ogletree, the Environmental Toxicology Extension Administrative Assistant for the consistently superior way in which she assembles and formats this newsletter and insures that there are very few errors. THANK YOU, one and all.
II.Inadvertent Contamination of Row Crops from Pesticides in Fog
News reports in the December 5, 1989, Sacramento Bee, Modesto Bee, and other sources highlighted the results of a California Department of Food and Agriculture (CDFA) study showing that residues of four organophosphate insecticides previously detected in samples of Central Valley fog have inadvertently contaminated row crops. The study was conducted in northern Stanislaus County and the pesticides presumably originated from dormant sprays of tree crops.
Although the headline, "Deadly residues hitchhike with fog: Study reveals new perils in shroud" in the Modesto Bee, warns of imminent hazard, a review of CDFA's report indicates that residues in the fog and on dill samples analyzed during December 1988 and January 1989 for the four pesticides - parathion, diazinon, chlorpyrifos, and methidathion - were at levels far below those known to cause human health effects. The maximum concentrations of insecticides found in the dill samples were 0.27 parts per million (ppm) for parathion, 5.1 ppm for diazinon, 0.45 ppm for chlorpyrifos, and 0.062 ppm for methidathion. The maximum allowable levels (tolerances) for these insecticides on commodities for which they are registered, with the exception of diazinon, are typically much greater than the maximum levels found. For example, the tolerance for parathion on tomatoes, citrus, and peaches is 1 ppm while the tolerance for chlorpyrifos is 1 ppm on peppers and 0.5 ppm on tomatoes. Diazinon tolerances are 10 ppm on sugar beets but less than 1 ppm on tomatoes, citrus, and peaches. Recent FDA studies have indicated that human exposure to diazinon in the diet is typically at a level of about one percent of the Acceptable Daily Intake (ADI), which is established by applying safety factors to the results of animal toxicology studies. It is doubtful that additional exposure to inadvertent residues of diazinon on row crops would cause human exposures to approach the ADI.
The maximum levels of these pesticides found in fog samples were 0.034 ppm of parathion, 0.24 ppm of diazinon, 0.0096 ppm of chlorpyrifos, and 0.011 ppb of methidathion.
All four insecticides cause toxicity in mammals at appropriate doses through their actions on the central nervous system by inhibiting cholinesterase enzymes. Poisoning symptoms are similar to the flu and include headache, nausea, vomiting, abdominal cramps, and increased sweating. Symptoms are reversible and can be treated using atropine and 2-PAM. Of the four insecticides, parathion and methidathion are the most toxic (i.e. they have the potential to cause poisoning at the lowest doses) and their use is restricted by CDFA. Neither diazinon nor chlorpyrifos is a restricted-use pesticide. The acute oral LD50s for the pesticides in rats are 4-13 mg/kg for parathion, 300-400 mg/kg for diazinon, 135-163 mg/kg for chlorpyrifos, and 25-54 mg/kg for methidathion.
The report in the Modesto Bee indicated that both parathion and methidathion are suspected cancer-causing agents (carcinogens). This is in contradiction to a 1987 report of the Environmental Protection Agency which indicated that methidathion is not considered to be a carcinogen while parathion is assigned to carcinogenicity category C (possible human carcinogen). In a recent report (Archibald and Winter, California Agriculture 43(6): 6-9, 1989), the total dietary risk for parathion in all foods, using conservative risk assessment models, was reported to be less than 12 excess cancers per billion.
It appears that the major impact of the study findings is an economic one rather than one of significant health consequences. At the present time, CDFA does not allow a food crop to enter commerce if any residue of a pesticide not registered for use on the commodity is detected, regardless of the level or the origin of the pesticide. Several of the pesticides used for dormant spraying of tree crops do not presently have tolerances established for row crops. The CDFA study, in fact, originated following findings during the winters of 1985/86 and 1987/88 that parathion, diazinon, chlorpyrifos, and methidathion residues were found on Central Valley crops that lacked tolerances. In such cases, CDFA did not allow the crops to be sold, resulting in major economic losses to the growers.
One possible regulatory solution to this problem that is currently being explored is the adoption of "generic" tolerances (set at low levels) for the pesticides that would apply to a variety of commodities for which no tolerances are currently established. While such a measure presumably has the support of growers and of CDFA, it faces an uphill battle due to the present state of pesticide and food safety concerns. While adoption of "generic" tolerances would make pesticide regulation more lenient, most current legislation calls for more stringent controls of residues in foods.
The findings of the CDFA study are valuable as they conclusively demonstrate that pesticides can be transported in fog by both regional and local mechanisms and can leave inadvertent residues on vegetation. An understanding of the complex factors of this transport is necessary as researchers strive to develop improved pest control methods that are less damaging to the environment and to human health.
Carl K. Winter
III.Lead Poisoning in Bridge Demolition Workers -- Massachusetts
In March 1988, lead poisoning was diagnosed in five of nine workers employed by a contractor to demolish a bridge spanning a river in western Massachusetts. A subsequent investigation by the Occupational Safety and Health Administration (OSHA) determined that from November 1987 through early March 1988 four of the affected workers had used acetylene torches to cut apart large sections of the bridge; the fifth had cut these sections into smaller pieces on a barge moored below the bridge.
In March 1988, two of the five workers involved in the cutting process sought medical advice: one had headaches and myalgia, and the other had nausea and arthralgia.
The OSHA investigation determined that paint covering the bridge contained 30% lead (by weight). Respirators available to the workers were not always equipped with cartridges that protected against lead fumes. The workers were not trained to OSHA standards in respirator use and wore the respirators infrequently. In addition, the employer had not provided clean work clothing or handwashing and eating facilities for the workers. OSHA cited the contractor for violating several regulations governing proper use of respirators.
Editorial Note: Based on findings from the 1981-1983 National Occupational Exposure Survey, an estimated 827,650 U.S. workers have potential work-related exposure to lead (excluding leaded gasoline). In the workplace, the respiratory tract is the major route of lead absorption. Clinical manifestations of occupational lead poisoning, which usually occur when BLLs exceed 40 mg/dL, can vary greatly in severity and include abdominal pain, anorexia (loss of appetite), fatigue, arthralgia (joint pain), headaches, irritability, depression, impotence, anemia, and hyperuricemia (high levels of uric acid in the blood as seen in gout). Encephalopathy (brain pathology), peripheral neuropathies (pathology of peripheral nerves), and impaired renal function have been reported, but are infrequently associated with occupational exposure.
Lead poisoning may occur when workers and employers fail to recognize the presence of lead or fail to adhere to accepted safety guidelines. Recent reviews of workers' compensation data and laboratory-based lead registries indicate that workers at highest risk for lead toxicity include persons who work in lead smelters, storage battery-manufacturing plants, plastic-compounding factories, and nonferrous foundries. Construction or demolition work that involves cutting through lead-coated metal structures, a process that generates high concentrations of lead fumes, can also present substantial risk for lead toxicity. Lead poisoning has been described in workers who repair and disassemble ships and roofs, dismantle elevated subway lines, and demolish and strip paint from bridges.
Construction workers in the United States are excluded from regulation under the OSHA Lead Standard. However, other OSHA regulations governing the construction industry require respiratory protection for workers who use torches to cut through toxic preservative coatings, such as lead-containing paints, and mandate engineering controls or respiratory protection for workers exposed to airborne lead at concentrations > 200 mg/m3.
As bridges in the United States age, they will require demolition or rebuilding. Construction workers engaged in these processes are at risk for hazardous lead exposure. Proper preventive measures, including engineering controls and appropriate use of respirators, should be carefully implemented. Physicians caring for construction workers should take thorough occupational histories and be aware that workers engaged in bridge demolition work may be at increased risk for occupational lead poisoning.
Reference: MMWR, Vol. 38 / No. 40, October 13, 1989.
IV.Radon Exposure Assessment -- Connecticut
In 1985, indoor air radon (radon-222) levels were found to be elevated in households in Pennsylvania. Following this discovery, the Connecticut Department of Health Services (CDHS) received inquiries from citizens who requested that their household air be tested for the presence of radon. Because information regarding radon exposures in Connecticut did not exist, CDHS initiated a series of surveys/projects to characterize this potential problem.
Because radon levels are typically highest during the winter, all homes were sampled for radon in December, January, and February. Radon levels ranged from 0.1 picocuries per liter (pCi/L) to 24.6 pCi/L (geometric mean: 1.3 pCi/L). Eleven percent exceeded the Environmental Protection Agency (EPA) maximum exposure guideline of 4 pCi/L. ( A curie, Ci, is defined as a radioactive decay rate of 37 billion disintegrations per second, dps. A picocurie is defined as 0.037 dps, or 1.8disintegrations per minute.)
Of the basements tested, 19% exceeded the EPA guideline of 4 pCi/L. The percentage of homes with levels >4 pCi/L varied between regions (boundaries defined by the estimated geologic potential for radon presence). The age of the house was the strongest predictor of indoor radon levels, with mean radon concentration levels increasing with the average age of the homes. Based on the results of the EPA-Connecticut survey, CDHS issued an advisory in August 1987 that all Connecticut homeowners should have their houses tested for radon.
Each of the three surveys detected higher radon levels in areas with granitic bedrock and lower radon levels in areas with sedimentary rock. Of all housing characteristics, only two (cinder-block foundation and house age) had statistically significant positive associations with radon levels. Energy efficient homes did not have higher radon levels.
Editorial Note: CDHS has collected data on indoor air radon levels in 5036 households. The data from the three Connecticut studies closely agree about both average radon levels detected and the percentage exceeding 4 pCi/L. Based on the risk model from the Biological Effects of Ionizing Radiations IV report, results from the EPA-Connecticut Survey indicate that, in Connecticut, radon exposure may account for 280 excess cases of lung cancer per year.
Until 1984, radon was considered a health hazard primarily for uranium and underground mining workers and for persons living in homes built on uranium mill tailing deposits or land reclaimed from phosphate mining. Based on EPA surveys of 1986-1989, however, exposure to radon and its short-lived decay products are estimated to exceed the EPA guideline (4 pCi/L) in >8 million homes located in 25 states and Native American lands.
In the United States, 5000-20,000 deaths from radon exposure may be occurring yearly. For persons who are exposed at the EPA guidance level of 4 pCi/L over a lifetime, overall risk for lung cancer is approximately 1%-3%. Risk for lung cancer from radon exposure is greatest among smokers, although risks for nonsmokers are also substantial (approximately 15 per 1000 exposed). Smoking appears to interact synergistically with radon in causing lung cancer. Consequently, cessation of smoking represents a crucial prevention measure for reducing lung cancer risk, particularly among radon-exposed populations.
Reference: MMWR, Vol. 38 / No. 42, October 27, 1989.
V.Update: Eosinophilia-Myalgia Syndrome Associated with Ingestion of L-Tryptophan -- United States
On November 9, 1989, CDC contacted all state health departments to inform them of a newly recognized syndrome involving severe, debilitating myalgias (muscle pains) and eosinophilia (^1000 eosinophils per mm3). Eosinophilia-myalgia syndrome (EMS) was reported initially from New Mexico and was associated with ingestion of L-tryptophan-containing products (LTCPs). To better characterize this syndrome and to assess the extent of the problem, CDC and state health departments implemented a national state-based surveillance system using a standardized case-report form. State health departments have telephoned numbers of EMS cases to CDC daily, then mailed completed case report forms; this results in a timely accumulation of total numbers but a lag in availability of detailed data.
As of December 6, 730 EMS cases have been reported to CDC from 48 states, the District of Columbia, and Puerto Rico. Only Alaska and South Dakota have reported no cases. Four deaths have been reported in patients who met the surveillance case definition and who used LT; one death has been confirmed as directly attributable to EMS, and the others are under investigation.
As of December 6, CDC has received completed report forms from 21 states with information about 64 cases fitting the case definition. Ages of these patients ranged from 14 years to 73 years (median: 44 years); 95% of patients were non-Hispanic white, 3% were black, and 2% were Hispanic. Fifty-two (81%) were female. Sixty-three (98%) had histories of LT ingestion preceding onset of symptoms; dosage ranged from 500 mg to 5000 mg per day (median: 1500 mg per day). Fifty-eight (91%) reported onset of symptoms during or after July 1989. Of the EMS patients reported thus far, 21 (33%) have required hospitalization.
(This recent development is of considerable interest from a toxicological perspective since it may indicate the presence of a highly toxic contaminant in LTCPs. The story has been unfolding for more than a month in the MMWR and updates on this syndrome will be printed in future issues of this newsletter.)
Reference: MMWR, Vol. 38 / No. 48, December 8, 1989
VI.Crystallized Chemicals Pose Explosion Hazard
Environmental Toxicology and Water Advisor
The Extension office in Sacramento County recently discovered itself in a potentially disastrous situation when a farm advisor failed to clean out his office after retiring. Among his personal belongings and assorted materials for work (papers, 3x3 slides) was a plain white paper bag. The Sacramento County Cooperative Extension (CE) office manager, not having any idea of the danger, pulled a bottle containing about 100-200 grams of crystalline Picric Acid* from the bag while in the process of cleaning up the office. Luckily, the newly hired Environmental Toxicology advisor knew what the compound was and how explosive it could be. The office manager was told to very carefully set the Picric Acid down and vacate the area.
The dilemma thickened when after making several calls to the University of California, Davis and various County agencies, the Sacramento CE office could not get any help with disposing of the Picric Acid. On the advice of a bomb demolition expert, the Picric Acid was placed in a bucket of water to lessen the chance of the most explosive crystals (those lining the lid of the jar) being detonated.
Concerned about how dangerous Picric Acid can be, on the following day the CE County Director requested the Office Manager to renew disposal efforts. At the CE County Director's request, the Office Manager called the County Safety Officer. It was then that the fire department (and therefore, the bomb squad) was notified by the County. When these emergency personnel arrived, both the CE and adjoining Agricultural Commissioner's offices were evacuated. The Sacramento CE County Director was now faced with an enormous dilemma: costs were quickly mounting, tempers flaring, programs interrupted, and a portion of the building was being cordoned off.
* Picric acid is commonly used to test for cyanide, for instance in the rumin contents of a cow.
Resolutions under these emergency conditions are never easy to come by, however, the bomb squad did remove the bottle of Picric Acid (for later detonation in a nearby field), the evacuation remained in effect only for the office containing the waste water (until the following day when the pH of the water was tested and it was determined to be safely disposable), and the County will be picking up most of the clean-up and disposal costs.
A similar event occurred in Sonoma County, with the exception being that it cost Sonoma a considerable amount of money. It is doubtful that it will be limited to just these two counties. BE AWARE! Reagent chemicals should not be stored in office space. Although inspections have been made of County CE chemical storage facilities, no program exists to monitor personal caches. All chemicals should appear on an office inventory and all should have current MSDS's or information on their use and potential hazards available. All chemicals have a "shelf-life", many become more reactive, toxic or explosive over time. Older labels may not adequately describe the hazard! If you find a chemical that you suspect is dangerous, and need assistance assessing the hazard, call Environmental Health & Safety (UCD) at (916) 752-1493; Dr. Craigmill at (916) 752-2936; or Allison Beale at (916) 366-2013. A few examples of hazardous chemicals are:
|Picric Acid||yellow crystals||explosive|
|Perchloric Acid||colorless||explosive hazard|
|Phosphorous||red, white||explosive hazard|
VETERINARY TOXICOLOGY NOTES
VII.Ethylenediamine Dihydroiodide (EDDI)
EDDI has been incorporated into animal feed and drug products for many years for both nutritional and therapeutic purposes. It has been formulated in salt/mineral mixtures and in liquids and powders for adding to feed or drinking water. EDDI has been used as a supplemental source of iodine and is considered generally recognized as safe (GRAS) for nutritional purposes when used at levels consistent with good feeding practices (21 CFR 582.80). EDDI products also have been marketed with claims for the treatment and prevention of certain diseases in several animal species, but primarily for "foot rot", soft tissue "lumpy jaw" and "wooden tongue" in cattle. However, all such EDDI products (including feeds bearing therapeutic claims) now are considered adulterated under sections 501(a) (5) or 501 (a) (6) of the act.
Based on the 1984 National Academy of Sciences/National Research Council (NAS/NRC) monograph, "Nutrient Requirements of Beef Cattle," CVM considers 10 mg/hd/day of EDDI to be an appropriate maximum level to be recommended on labeling of EDDI-containing products intended for routine supplementation of iodine in the diet of both beef and dairy cattle.
All animal products containing EDDI that bear claims for treatment or prevention of any animal disease (other than the prevention of iodine deficiency) are considered unapproved new animal drugs or feeds bearing or containing unapproved new animal drugs and are adulterated under section 501 (a) (5) or 501 (a) (6) of the act, respectively. (Abstracted from FDA guide 7125.12).
--As seen in the Utah State Univ. Vet. Newsletter, February, 1989.
Reference: Ohio Veterinary Newsletter, September 1989.
VIII.The Regulation of Food Additives in Animal Feeds
The Food and Drug Administration's Center for Veterinary Medicine (CVM) regulates the use of food additives, as well as drugs, in animal feeds. Many researchers and manufacturers are aware of the procedures for the regulation of drugs used in animals for disease treatment/prevention and for increasing animal productivity but are not aware of what constitutes a food additive and what steps are necessary to gain approval of a food additive.
In addition, many people in the animal industry confuse the terms "food additives" and "feed additives." The latter has no legal meaning. It is generally used to refer to drug products which are added to animal feeds.
Food additives are non-drug substances that affect food/feed quality, such as stabilizers, antioxidants, nutrient sources, etc., that are not considered generally recognized as safe (GRAS) for that use. Additives considered GRAS for one use are not automatically GRAS for a different use, especially when production claims are being made on the labeling. Production claims include such things as increased feed efficiency, increased milk, meat or egg production and increased reproductive efficiency.
Where the additive is a food (i.e. provides nutrition, taste or aroma) and the manufacturer wished to make production claims in the labeling, the additive is considered a food additive. If the additive is not a food, then it will be regulated as a drug when production claims are made. Claims such as reduced heat stress and reduced incidence of mastitis are considered medical/therapeutic and will cause any substance, food or non- food, to be regulated as a drug.
Food additives must be shown to be safe to the target animal, to the environment, and edible products from the animal shown to be safe for human consumption. The type of safety studies required will depend on the substance, its chemical nature and its history of use for other purposes. For a new substance that has never been fed to animals before or has a chemical nature that is similar to other substances known to be toxic, mutagenic, teratogenic or carcinogenic, a full range of toxicological, residue, and environmental safety studies similar to those done for a new animal drug will probably be required. For a substance that has a history of safe use for another purpose, target-animal safety studies required may be less extensive.
Also, a food additive must be shown to be effective for its intended use. What research scientists and what regulatory scientists think constitute a good study do not always agree. There is a tendency among research scientists to try to get as much information as possible from every study. This is understandable considering the difficulty in obtaining grants and/or other monies to support research. However, it can lead to studies where different types of treatments are being compared at the same time, which may cause confounding effects, making it difficult to separate out the effects of the treatment that is under consideration by the regulatory agency. On the other hand, the regulatory scientists in CVM prefer studies comparing one treatment to a control or controls (positive and negative). In addition, the Center likes to see these studies repeated in three different geographic locations. Since the Center will not approve a level of a food additive higher than is necessary to give the intended effect, titration studies are also needed. CVM will review protocols for investigational studies of new food additives, if requested, and comment on their suitability. We highly recommend this be done when ever possible.
Any researcher who is conducting trials utilizing an unapproved food additive is required to submit an Investigational Food Additive Application to CVM. And if you are unsure if the substance or product you are studying is a food additive, it is best to inquire as to its status before beginning your research. The information needed differs depending on whether the animals will be sent to slaughter, used to produce milk or eggs for human consumption or destroyed. If they are going to be destroyed, a letter describing the substance or product to be studied and the study protocols will often suffice. If the animals are to go to slaughter, however, information and data showing that the edible products from the experimental animals will be safe for human consumption is required. And depending on the substance a withdrawal period may be required. Studies where the animals go to slaughter are usually for efficacy, not safety studies. Any unapproved food additive that is being shipped across state lines for use in an investigation study must bear a label stating that it contains a new food additive for use only in investigational animals for research and not for use in humans. Edible products of investigational animals are not to be used in food unless authorization has been granted by the FDA. Such authorizations are coordinated with the US Department of Agriculture who may sample the animal at the time of slaughter.
What constitutes a food additive petition? The Code of Federal Regulations 21 part 571.1 outlines the contents of a food additive petition.
A food additive petition consists of 8 sections, all of which need to be addressed satisfactorily before a food additive can be approved. These sections are:
A. The name and all pertinent information, including its chemical, physical and biological properties. This includes manufacturing and quality control information.
B. The amount of the food additive proposed for use and its intended purpose or purposes. This includes a draft copy of proposed labeling.
C. Efficacy data.
D. Assay methodology. Methods for detecting the additive in feed and animal tissues.
E. Safety studies (human and target animal).
F. Proposed tolerances, if required. This refers to residues in animal tissues.
G. A draft regulation covering the proposed food additive and its uses.
H. Either an environmental assessment or a claim for categorical exclusion, with information to back it up.
Once a petition is submitted, the FDA has ten days to decide if it is acceptable for filing. A petition is only acceptable for filing if all of the above sections are addressed. The agency then has 180 days to decide whether to approve the petition. It should be noted that all the information in a food additive petition is available to the public once the petition is approved. In addition, once approved, anyone who meets the specifications in the regulation can manufacture and market the food additive. The only protection the sponsor has is its patent, assuming they have one. Applicants can apply for patent extension, based on some of the research time spent getting the product approved.
In conclusion, we hope that the research community will work with us to provide for the approval of new food additives that have utility and are safe to the animal, the consumer and the environment and to discourage the use of food additives whose safety and/or efficacy have not been proven.
--Presented at the American Society of Animal Science and American Society of Dairy Science Annual Meeting, Lexington, KY,
August 1, 1989. D.M. Waltz, W.M. Knight, and G. Graber. Center for Veterinary Medicine, Food and Drug Administration, Rockville, MD 20857.
Reference: Ohio Veterinary Newsletter, September, 1989.
IX.Extra-Label Use of Drugs
The question might be asked, what does the term extra-label use mean? In short, extra-label use occurs when the user of a drug product does not follow the directions that are on the labeling of the product. You might ask, why is this issue important? It is important for two reasons: (1) extra-label use takes one off into a land of unknowns and (2) it is a violation of the Food, Drug, and Cosmetic Act. The latter point which has to do with the law, is a point that is not widely known. I find that most audiences do not believe, based on their own reasoning, that the law would insist on adherence to label directions. The Federal law in fact does require that of all of us. The same provision, however, does not exist in the portion of the FD&C Act which deals with drugs for humans.
Based on the knowledge that a veterinarian, on occasion, will find the need to use an approved drug other than labeled, the Center for Veterinary Medicine (CVM) has developed a policy to exercise prosecutorial discretion. This policy is called the extra-label use policy for animal drugs. Thus, regulatory action for extra-label use would not ordinarily be considered, provided the following criteria are met and precautions observed:
1. A careful medical diagnosis is made by an attending veterinarian within the context of a valid veterinarian / client / patient relationship;
I want to familiarize you with the American Veterinary Medical Association's (AVMA) definition of a veterinarian / client / patient relationship. A valid veterinarian / client / patient relationship will exist when:
a. The veterinarian has assumed the responsibility for making medical judgments regarding the health of animal(s) and the need for medical treatment, and the client (owner or other caretaker) has agreed to follow the instructions of the veterinarian; and when
b. There is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s). This means that the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) and/or the veterinarian makes medically appropriate and timely visits to the premises where the animal(s) are kept; and when
c. The practicing veterinarian is readily available for follow-up in case of adverse reactions or failure of the drug therapy to be effective.
2. A determination is made that (a) there is no marketed drug specifically labeled to treat the condition diagnosed, or (b) drug therapy at the dosage recommended by the labeling has been found to be not clinically effective in the animals to be treated;
3. Procedures are instituted to assure that identity of the treated animals is carefully maintained; and
4. A significantly extended time period is assigned for drug withdrawal prior to marketing meat, milk, or eggs; steps are taken to assure that the assigned timeframes are met; and no illegal residues occur.
Since extra-label drug use can be a cause of violative tissue residues, we need to discuss the issue of residues further. As you all know, the presence of illegal residues of drugs in meat and/or milk is a potential human health problem. Protection of the public while permitting the food producer to realize the economic benefits of safe and effective drugs is one of the responsibilities of the Food and Drug Administration (FDA). CVM's tissue residue program is a public health program with the goal of assuring that consumer exposure to drug residues in edible tissues of food animals is minimized. The program focuses on prevention and regulatory enforcement in reducing the prevalence of illegal residues.
One function of our program is to analyze the causes of residues in order to recommend strategies for preventing future repeat violations. In many cases we are able to obtain corrections through educational efforts that improve the producer's drug use and residue avoidance procedures. The results of FDA investigations of violative residue reports indicate that the overwhelming majority are caused by human error. Failure to observe the drug withdrawal time, failure to follow label directions, and the use of unapproved products are common causes, many of which are related to extra-label use. In the majority of instances the animal producer has caused the illegal drug residue. In livestock production, the idea that "it's my animal and I can do whatever I want" is simply not acceptable today to the consumer of animal-derived food products. In the consumers' eyes, no residues are acceptable.
CVM has recently completed a review of FY 1988 follow-up investigation reports. A total of 460 reports are included and all slaughter classes are represented. With the exception of sulfamethazine in market hogs, the major concern for residues is antibiotics in the bovine, but more specifically culled dairy cows and fancy veal. Violation rates were generally less than 3% of slaughtered swine, cull dairy cows and veal calves. In all other classes, rates were well below 1%. To get into more specifics, intramuscular (IM) injection accounted for 60% of the residue cases, and cull dairy cows were the largest contributor of residues in this category. Oral administration accounted for 28% of the violations and many of these occurred in the bob veal.
Intramammary infusion accounted for 9% of the residue cases, all of which occurred in cull dairy cows.
Returning specifically to our extra-label discussion, it is important to note that the exempting criteria do not provide for extra-label drug use by laypersons. Also, certain drugs may not be used in treating food-producing animals even under the extra label conditions. These include DES, chloramphenicol, dimetridazole, and ipronidazole. In addition, the criteria do not provide for extra-label use of drugs in animal feeds to improve rate of weight gain or feed efficiency, or for routine disease prevention or treatment. That means there is no extra label mixing permitted at the feed mill. This is true for commercial mills that sell feed, as well as those mills that mix feed for their own animals. FDA is not likely, however, to be involved with the on-the-farm situation unless the operation is registered with FDA or an illegal tissue residue is found in the marketed animal.
We recognize there are occasions when the extra-label use of drugs by veterinarians is the appropriate course of action. The policy developed by CVM is a common sense approach that will play a key role in curtailing extra-label use of any public health significance. However, where food animals are concerned, the best practice is the use of approved drugs at approved dosages. When necessary to deviate, due to lack of availability of a drug for a particular condition or the ineffectiveness of an approved dosage level, it is incumbent upon everyone to follow the instructions given by your veterinarian. This includes special identification of the animals treated, compliance with the extended withdrawal period, and keeping adequate and accurate records concerning the treated animals.
No discussion of extra-label drug use is complete without spending a few minutes on the subject of the sale and distribution of veterinary drugs. First, as many of you know, most drugs for use in food animals are over-the-counter (OTC) drugs. By actual count of approved food animal drugs, approximately 92% of these are for over-the-counter use, and only 8% are reserved for use by or on the order of a licensed veterinarian. For companion animals, including horses, quite the opposite situation exists. By far the majority of companion animal drugs are labeled with the prescription legend. There has been somewhat of a breakdown in the system for controlling prescription (Rx) drug sales for food animals. The sale to a layperson of an Rx product may be made only by or on the order of a licensed veterinarian. Any such sale must result from a proper veterinarian/client/patient relationship, as discussed earlier in detail.
We at CVM do believe that prescription drugs must be under the supervision of a licensed veterinarian. If those products are sold directly to the animal production unit, a veterinarian must have been involved in the thought process that caused the drugs to be ordered for a particular use. Orderly and supervised use of veterinary prescription drugs is essential to the integrity of the food product as well as essential to the health of the animal. How can you tell the difference between an OTC product and a prescription product? The label on a prescription drug must contain the statement, "Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian". Some products are labeled to relate to marketing and contain such statements as "for veterinary use only", "Restricted drug", or "Sales to licensed veterinarians only". These products are for over-the-counter marketing even though they contain these statements. A veterinary prescription drug always contains the caution statement referred to above.
There are no prescription drug premixes. Prescription drug status is designated for a drug product because adequate directions for lay use cannot be written. It has been a long standing agency position that adequate directions for use can be written for drug premixes; thus, their over-the-counter status. It is also not acceptable for a veterinarian to enlist the services of a feed mill to mix drugs into a feed on a "prescription" basis. The feed mill may only manufacture medicated feeds at levels and uses provided for in the animal drug regulations.
Many of these prescription products are potent drugs, and most are capable of creating illegal residues if not carefully handled. Illegal sales practices concerning veterinary Rx drugs continue. It is our belief that many suppliers, such as mobile peddlers, feed stores, and mail order companies are selling Rx animal drugs without the required prescription, including prescription drugs used in food-producing animals. Violative tissue residues have been linked to illegal sales of Rx animal drugs by mobile peddlers. In order to expand our efforts in bringing this industry into compliance, we are now directing attention to these above mentioned segments, which in the past have received little or no attention in many regions of the country.
I believe that this will also cause a reduction of "magic mixtures" and so-called "cocktails" with names like "Bloody Mary", or "Mastitis Magic Formula #1". You can be sure that the FDA and, on occasion, the Justice Department of the Federal Government will continue to discourage these activities through regulatory actions. I hope that you share our concern for the risk to public health and to animal health when these unapproved concoctions are used. If a drug is shipped in interstate commerce and used in animals, it should be an FDA-approved animal drug. One has very little assurance of the quality and identity of a product that is not approved. We encourage each of you to be extremely careful when dealing with drug mail order sales and mobile drug dealers.
Each of you has the ability to create an atmosphere surrounding animal drug use that instills responsibility. Your actions each day have an influence upon the consumer's perception of the food animal production industry. Just as a chain is only as strong as its weakest link, everyone in the animal production chain must do his/her best to produce a product that is free of violative residue. You are an important link in that chain, and you have a major role to play in supporting and promoting the concepts of quality control and proper drug use. We at CVM would like to work with you to help you fulfill that role. -- Presented by John K. Augsburg, DVM, MPH, Special Assistant to the Director, Center for Veterinary Medicine, FDA, at the 9th Annual Kentucky Ruminant Nutrition Workshop, October 12, 1989, Bardstown, Kentucky.
Reference: Herd Health Memo, #5, November 1989.
X.New Private Sector Support for 4-H Veterinary Science Awards Program
We are very pleased to announce PITMAN-MOORE, INC. as the new sponsor in 1990 of the National 4-H Veterinary Science Awards Program.
Pitman-Moore, Inc. is one of the world's largest animal health and nutrition companies with a broad line of products for livestock, poultry and companion animals.
Through this sponsorship, Pitman-Moore, Inc. will provide medals of honor at the county level, certificates, pins and trips to the National 4-H Congress in Chicago for state winners and six educational scholarships of $1,500 each to national winners.
Through the Veterinary Science program, 4-H members gain a better understanding of their animal's health care needs. 4-H'ers learn how to keep their animals healthy, how to nurse them when they are ill, and how to know when it is time to call a veterinarian. It also gives 4-H members the opportunity to explore the field of veterinary medicine as a career.
We will appreciate you taking time from your schedule to acknowledge Pitman-Moore, Inc. as a new private sector donor to 4-H.
Please send your letter to: Dr. M. Blake Ingle
2315 Sanders Rd.
Northbrook, IL 60062
Reference: Letter from K. Russell Weathers, Vice President, Program Services Division, National 4-H Council, October 30, 1989.
Statewide Pesticide Coordinator
Environmental Toxicology and Water Advisor