UNIVERSITY OF CALIFORNIA
ENVIRONMENTAL TOXICOLOGY NEWSLETTER
Vol. 7 No. 3 October 1987
XI. PLANTS, PESTICIDES AND OTHER TOXIC CHEMICALS
Table of Contents
I. Serum Dioxin in Vietnam-Era Veterans - Preliminary Report II.
Appointment of Carl K. Winter - UCR
Greetings from "down under" to all readers of the Environmental Toxicology Newsletter! Yes, there is work during a sabbatical and hopefully after it too. Having been in Australia now for almost four months, it seems like no time at all. Within two days after arriving here, headlines appeared in the newspapers about Australian export beef being tainted with pesticide residues (DDT, dieldrin, etc.). This caused a considerable stir all throughout Australia from livestock producers to their state and federal government agencies. The use of certain of the chlorinated hydrocarbon insecticides had been allowed until recently for specific uses on things like sugar cane and bananas. The use of these persistent pesticides has not been allowed on forage crops or anything that is supposed to be fed to livestock, and real questions remain as to how the chemicals have come to be in the animals.
Much of the work that I have done in the Veterinary Extension program has been on a USDA funded project called the Food Animal Residue Avoidance Databank (FARAD). FARAD was developed as part of the USDA Extension Service Residue Avoidance Program (RAP) as a collaborative effort with the University of Florida, North Carolina State University and the University of Illinois. FARAD contains considerable information about issues which can affect chemical residues in food animals and their products, especially information about the absorption, distribution, metabolism and excretion of chemicals from livestock. Dr. Alan Seawright, with whom I am working during this part of my sabbatical, instantly put me in touch with all of the people he knew who might want information to assist with this problem, and because I have the complete FARAD with me on a Compaq Plus Portable microcomputer, I have been in high demand to answer questions ever since! The usual types of questions have arisen from this incident such as "How long will it take to get down below the tolerance level (called the Maximum Residue Level, MRL here)", "What kind of levels would animals have to ingest to exceed the MRL?", and so forth. Because of the wealth of data in FARAD, it has been possible to provide the Aussies with some answers, and help them to address possible sources of the residues.
The Australians have mounted a concerted effort throughout the country to come to grips with the residue problem because their beef exports are a major export item. At a conference I recently attended in Sydney, one of the veterinarians from the Department of Primary Industries related that to that date, more than 22,500 samples had been tested since May, 1987, and that they are now residue testing 1 per hundred of slaughtered cattle, 1 per 1000 sheep and 1 per 30 swine! All of the residue testing is being funded by the meat producers, which will ultimately result in higher meat prices. This is an incredible number of tests for chlorinated hydrocarbons in meat. Based on what I can ascertain, they have done more pesticide residue analysis in the last 6 months than the USDA Food Safety and Inspection Service does on U.S. meat in 5 years, and possibly ten! The government agencies have instituted a program to test every cattle farm in Australia, and to quarantine those which show pesticide levels in their animals which exceed the MRLs. So far this has led to the quarantine of more than 30 ranches, and it is likely that the numbers will go higher. It will be interesting to find out the sources of the contamination since there has been considerable speculation about this, with very little hard information available.
Of particular interest to me has been the fact that the residue levels in most cases only slightly exceeded their MRL's, and that at least for dieldrin, their MRL (0.2 ppm) is lower than the action level in the U.S. (0.3 ppm). During the course of presentations, demonstrations and discussions about FARAD and the residue problem, I have come to get a much more complete understanding of the way pesticides and drugs are approved for use in Australia, and that is the focus of the next short article about differences in the Australian and U.S. systems.
Pesticide and Animal Drug Registration in the U.S. and Australia: A Comparison
There are many more similarities in the data requirements and procedures for registering chemicals than there are differences, thus I will only concentrate on what I feel are notable differences in procedure and data requirements. One of the most striking differences is the size of the bureaucracies involved; the U.S. EPA is huge, and the Australian Technical Committee on Agricultural Chemicals (TCAC) is relatively small. Their responsibilities are similar, and that is to evaluate and approve the use of agricultural chemicals as pesticides in order to insure environmental safety (including human health). This covers all aspects of use and disposal. All chemicals that are to be considered for use must be approved by the EPA or the TCAC before state registration for use can occur. In Australia there appears to be a greater reliance on the TCAC in that the state's here do not appear to have their own "mini-EPA's" (like the CDFA has). Thus clearance through the TCAC virtually assures state registration, however one state may well restrict the use of a registered chemical more severely than another. The chemical company who registers a pesticide in Australia only has to submit one data package to the TCAC, whereas in the U.S., some states (like California) may require the submission of complete data packages for evaluation.
Another difference in the systems is the way a chemical can be removed from use. In the U.S. there are occasional emergency cancellations, but more often the process of canceling a registered pesticide may take some time. In Australia, if the TCAC decides to cancel a particular chemical's use, it simply does so and notifies the states who then cancel their approvals as well. One of the people I met on the TCAC in Canberra mentioned that they were astounded that it took so long for the U.S. to get rid of certain compounds that they had canceled virtually overnight.
Another difference between the U.S. and Australia has to do with the division between animal drugs and pesticides, and agricultural pesticides. The federal government of Australia also has a Technical Committee on Veterinary Drugs (TCVD) which handles the registration of all products that may be used on or given to animals. The TCVD is responsible for registration of drugs given to animals to control diseases, and also has responsibility for registering pesticides that may be applied externally to animals to control ectoparasites. In the U.S., the Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) has the responsibility for registration of all animal drugs, whereas the EPA has charge over pesticides that are applied externally to animals. This arrangement has produced some confusion in the past within the IR-4 Animal Drug Program when each agency said that one particular use of a chemical to control a disease in fish, was actually within the power of the other! No such confusion can occur in Australia, and all in all, I think their system of responsibility for all animal products within one agency has great merit.
The last difference that I think is of note has to do with the "political" nature of the organizations within each country. In the United States, the persons who have overall charge of the FDA and EPA are political appointees. Changing administrations can bring changes of the directors who have ultimate control of decisions about promotions, assignments, and even the number of staff necessary within each section of these bureaucracies. Thus it can be said that the staff of the U.S. organizations are in a sense, under some degree of political pressure. It appears that in Australia this is not at all the case, and that the people staffing the TCAC and TCVD are quite removed from political pressure, at least that is what I have been told by them when I asked. I would not deign to make a judgment about which system is better, there are however differences in operations which can affect decisions about chemicals. One thing that I did notice during this "residue crisis" with export beef, is the very coordinated effort put forth by all aspects of the government and public sector to remedy the problem. Within two weeks, registration of the persistent chlorinated hydrocarbon pesticides for all uses (that I know of) were canceled, and efforts begun to organize their collection and disposal.
That concludes my very brief comparison of the U.S. and Australian systems. As I discover more about the workings of their institutions I will include it in future newsletters. If you have any particular questions relating to this article, please forward them to Sandy Ogletree, the Environmental Toxicology Extension Administrative Assistant. G'day.
I. Serum Dioxin in Vietnam-Era Veterans - Preliminary Report
Agent Orange, a defoliant used in Vietnam, was a mixture of 2,4-D (2,4-dichlorophenoxyacetic acid) and 2,4,5-T (2,4,5- trichlorophenoxyacetic acid). During manufacture 2,4,5-T was contaminated with TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a compound with marked toxicity in some species of experimental animals. In 1979, the U.S. Congress responded to concerns of Vietnam veterans by passing Public Law 96-151 mandating epidemiologic studies of the possible health effects on Vietnam veterans of exposure to herbicides and their associated dioxin contaminants. In 1983, CDC developed a protocol for a historical cohort study (the Agent Orange Exposure Study) of U.S. Army veterans who had served in heavily sprayed areas of Vietnam. The protocol specified that the degree of exposure to Agent Orange be based on a score estimating the "likelihood of exposure" and calculated from information in military records.
Men who served in the III Corps military region (around Saigon) during the period 1967-1968 were selected for study because this region was heavily sprayed during that time. The U.S. Army and Joint Services Environmental Support Group (ESG) found that 65 U.S. Army combat battalions had spent at least 18 months in the III Corps area during the period 1967-1968. The ESG abstracted daily locations of companies within these battalions from military records and obtained personnel records of men who had served in those companies. Using existing records of each application of Agent Orange by fixed-wing aircraft, helicopter, or ground-based equipment and ESG troop location data, CDC developed several different methods for computing exposure scores for each man. These methods were based on each man's daily proximity (in time and space) to recorded Agent Orange applications.
Subsequent evaluation of military records by CDC and ESG revealed that daily tracking of individual soldiers was not always possible. The ESG evaluation also suggested that many helicopter and ground-based sprays, which were often near troops, were not recorded. Consequently, CDC has conducted a validation study using current TCDD levels in serum as a biological marker to determine whether scores based on military records or on veterans' self-assessed exposures to herbicides could identify those veterans who had received heavy exposure in Vietnam.
During 1986, CDC's Division of Environmental Health Laboratory Sciences, Center for Environmental Health, developed a method for measuring TCDD in human serum. The measurement, which is based on lipid weight, is highly correlated with paired measurements of TCDD in adipose tissue (r = .98). The same laboratory subsequently used paired sera (drawn in 1982 and 1987) to estimate the half-life of the TCDD body-burden in man as approximately 6-10 years (CDC, unpublished data). The sera came from Air Force personnel involved in spraying Agent Orange in Vietnam during 1968. Some of these sera still show markedly elevated TCDD levels in 1987. These new developments suggest that only about 2 to 2.5 TCDD half-lives have elapsed since potential exposure in Vietnam and that serum TCDD can serve as a biological marker for previous Agent Orange exposure. These findings are the basis for the study of U.S. Army veterans reported here.
Vietnam veterans invited to participate in this study had served in at least one of the 65 selected battalions between October 1966 and March 1969. They were chosen from the 9,727 men whose records were sufficiently complete for exposure scoring and who met the original selection criteria proposed in 1983 (e.g., only a single tour of duty in Vietnam and pay grade of E1 to E5 at discharge). The exposure score used to select Vietnam veteran participants was the total number of occasions on which the veteran's unit was within 2 km of a documented Agent Orange spray within 6 days after that spray. This score is based on the assumption that TCDD undergoes rapid degradation on vegetation. All but 10 of the 314 men with a high exposure (a score of 5 or more) were invited to participate in this study. A stratified random sample of 235 of the 1,351 men with a score from 1 to 4 were invited, and a sample of 440 of the remaining 8,062 all of whom had a score of 0, were invited. These men averaged over 300 days of service in Vietnam. A stratified random sample of 200 non-Vietnam veterans of the same era were invited as a comparison group. While they did not have Vietnam-related exposure to Agent Orange, their demographic and other personal characteristics were similar to the Vietnam veterans.
Of the 979 invited Vietnam veterans, 871 (89%) completed telephone interviews, and 665 (68%) also completed medical examinations and gave blood for TCDD measurement at CDC. Those reporting health problems in the telephone interview were more likely to participate in the examinations and blood sampling than were those reporting good health. Of the 200 non-Vietnam veterans invited, 103 (52%) participated fully. This lower participation rate does not affect exposure scores or TCDD levels in Vietnam veterans. Each participant underwent a detailed interview regarding military and civilian exposures to herbicides. While 25% of Vietnam veterans reported direct exposures (present during spraying or handled spraying equipment) and 70% reported indirect exposure (walked through defoliated areas), 6% of non-Vietnam veterans reported such exposures. Those who were both interviewed and examined were similar to those who were interviewed only.
The preliminary TCDD distributions, which are based on the first 519 specimens processed, represent a 68% random sample of the participants. All of these men except one had TCDD levels (based on lipid weight) below 20 parts per trillion (ppt), which is considered the upper limit for residents of the United States without known TCDD exposure. There was no significant difference among the three Vietnam veteran exposure groups selected on the assumption of short environmental availability of TCDD (p = .83). Likewise, no association was found between TCDD levels and two other methods of scoring exposure that were chosen to reflect a longer environmental persistence of TCDD (one method accounted for the distance from the spray, without regard to the time since spraying, and the other accounted for total days spent in heavily sprayed areas). Finally, no association was found between TCDD levels and self-perceived herbicide exposure in the military (either direct exposure or delayed exposure). The median TCDD levels for all exposure groups were between 3.5 and 4.3 ppt. Furthermore, TCDD medians for Vietnam veterans (median = 3.8 ppt) and non-Vietnam veterans (median = 3.9 ppt) were virtually the same. A full report will be published after TCDD measurements have been completed for all participants and the full report has been reviewed by the Agent Orange Working Group of the Domestic Policy Council (Executive Branch) and by the Congressional Office of Technology Assessment.
Editorial Note: The purpose of this study was to determine whether estimates of exposure based on military records or on interviews of U.S. Army veterans can identify those with heavy exposure to TCDD. Serum TCDD levels measured in 1987 were not associated with any of the indirect exposure scoring methods evaluated. Because of the purpose of the study, men with higher exposure scores were deliberately over-sampled. The distribution of TCDD levels reported here cannot be generalized with confidence to all U.S. Army Vietnam veterans since the study did not use a random sample of all such veterans.
While CDC was processing sera from the U.S. Army veterans reported here, it was concurrently processing sera from other groups with known occupational exposure to dioxin prior to but not after 1970. Some of those who were occupationally exposed had TCDD levels more than 30-fold higher in 1987 (CDC, unpublished data) than the median levels of approximately 4 ppt reported here for Vietnam veterans.
The distribution of TCDD levels for the Vietnam veterans, with all but one below the upper limit for unexposed U.S. residents, suggests that few of the participants in this study have had unusually heavy dioxin exposure. No threshold level has been determined as yet for the health effects of TCDD on humans.
MMWR, Vol. 36/No. 28, July 24, 1987
Author Note: The underlined and highlighted portions of the article above were chosen by me for emphasis. This study is of particular significance to the controversy about the role of dioxin in the well documented health problems found in many Vietnam Veterans. I think it is also very important in relation to the difference between people's perception of exposure to toxic substances, and actual chemical evidence of such exposure. This study also provides some very useful information about the biological half-life of TCDD in humans (6-10 years), indicating that at the levels found in highly exposed humans, elimination is very slow, most likely due to the sequestration of TCDD in fat and fatty tissues.
II. Appointment of Carl K. Winter as Extension Toxicologist, UCR
I am very pleased to have the opportunity to announce the recent appointment of Dr. Carl K. Winter as Extension Toxicology Specialist at UC Riverside. Carl received his Ph.D. in Agricultural and Environmental Chemistry from UC Davis in June, 1987. Prior to pursuing his Ph.D. he had worked for 4 years at the California Department of Food and Agriculture in the Worker Health and Safety Unit and was involved in many studies on human exposure to pesticides. Carl will be housed in the Toxicology Department, Division of Toxicology and Physiology in the Department of Entomology, chaired by Dr. Roy Fukuto. Carl is on board and ready to help with any problems or questions that arise in the counties. I know that you will find him knowledgeable, energetic and enthusiastic about tackling toxicology problems and public education programs.