COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIA
ENVIRONMENTAL TOXICOLOGY NEWSLETTER

Vol. 12 No. 3 - July 1992

Current Research Programs in the Environmental Toxicology Department at UCD

Introduction

This issue of the Environmental Toxicology Newsletter will focus on the faculty in the Environmental Toxicology (ETOX) Department at UCD. The purpose is to stimulate interest and involvement of county-based CE academics in those programs which relate to their local needs, and to elicit input from the county-based staff about applied research projects in which the ETOX faculty may become involved.

The ETOX department is currently composed of seven full-time faculty (including two Extension Specialists), five members with partial appointments and three emeritus professors. Despite the department's small size, it is the home of the Pharmacology-Toxicology Graduate Group, an NIEHS Graduate Training Grant in Toxicology, and an NIEHS Environmental Health Center Grant.

The descriptions of research were solicited from the faculty and "massaged" by the editor. If you have any questions concerning our programs, please contact the faculty member directly, or one of the Extension Specialists.

Highlight on Environmental Toxicology

Arthur Craigmill, CE Specialist

In addition to publishing this fine newsletter, my applied research activities fall into two major categories; veterinary toxicology and environmental toxicology. I serve as the Western Region Coordinator for the IR-4 Minor Use Animal Drug Program. The purpose of the program is to provide the data necessary for the approval of drugs for use in minor species (sheep, goats, game birds, aquaculture, etc.) and many of the studies needed are performed on the UCD campus. Another veterinary toxicology program is the Food Animal Residue Avoidance Databank (FARAD). FARAD was developed in collaboration with the University of Florida, the University of Illinois, and North Carolina State University as part of the Residue Avoidance Program in 1982. The purpose is to provide a centralized mechanism for preventing chemical residues in food animal products and to respond to animal contamination problems. The project involves the collection of all known data on the pharmacokinetics (absorption, distribution, metabolism and excretion) of chemicals in food animals.

My applied research programs in environmental toxicology have included bioremediation of pesticide waste at hazardous waste sites, and an assessment of the effectiveness of such remediation. This work is currently being done in collaboration with Dr. Dave Hinton in the School of Veterinary Medicine, using a fish model for toxicity. I am collaborating with Mike Stimmann, Terry Prichard and Phil Osterli on a project to measure kelthane residues in irrigation runoff after kelthane application to beans. In collaboration with numerous Home Advisors and other Advisors (most notably Allison Beale, Environmental Toxicology and Water Advisor, Sacramento County) we are using the University of California Quick Lead Test (UCQLT) to test ceramicware for leachable lead. A fuller description of the status of this project will be the lead (no pun intended) article in anotherissue later this year.

Donald Crosby, Professor Emeritus

Dr. Crosby is an Emeritus Professor within the department and remains very active with his research and graduate training program. Dr. Crosby's principal area is environmental chemistry, but his interests and expertise cover many areas of environmental toxicology, with a special emphasis on photodegradation, the marine environment, and ecotoxicology. A few examples of his contributions include: the prediction of pesticide persistence in water and the effects of sunlight on persistence; the environmental fate of insecticides and their effects on aquatic organisms; the environmental fate and lateral movement through soil of herbicides; the measurement of the intensity of ultraviolet radiation under field conditions and its effects on chemical reactions (photolysis); the significance of the aquatic surface microlayer in pesticide movement and fate in the environment; the biodegradation of chemicals by mussels; the effects of chemicals on and biodegradation by sandy beach organisms; the movement and bioavailability of pesticides in Monterey Bay shellfish; and the effect of pollutants on reproduction in the giant kelp Macrocystis. At one time he was active in research on poisonous plants and still presents lectures on the topic.

Dr. Bruce Hammock, Professor

Also affiliated with the Department of Entomology.

Numerous studies have shown that on the average, the American diet is free of dangerous residues of food borne toxins. However, we lack the technology to analyze a significant number of samples of domestically produced or imported food. Dr. Hammock and coworkers have pioneered the development of class and compound specific immunoassays for the rapid analysis of toxins in food matrices. These could be effectively employed in monitoring the correct use of pesticides in the field, residues in raw materials entering a processing plant or monitoring residues in final food products. These assays complement classical chromatographic technology at a small fraction of the cost. They will result in enhanced food safety for the consumer and reduced analytical costs.

Effective insect control is essential for profitable food production. However, resistance of pest insects and public concern over synthetic chemical insecticides in food is limiting our ability to control pests. In response to this problem the laboratories of S. Maeda and B. Hammock in Entomology have developed two separate approaches to engineering insect specific viruses to kill the major insect pests in the U.S. both specifically and quickly. The first target is the highly destructive cotton bollworm (H. virescens, and its relatives). These recombinant viruses kill pest insects much more quickly than wild type viruses and offer efficient control of insecticide resistant pests without pesticide residues or environmental damage. These materials will be field tested in the United Kingdom next year.

Dr. Dennis Hsieh, Professor

During the last few years Dr. Hsieh has directed the preparation of 12 health risk assessment documents on priority chemical contaminants in California drinking water for the California Department of Health Services. Some of the chemicals covered were DBCP, EDB, pentachlorophenol, trichloroethylene, carbon tetrachloride, and toluene. The information developed was used in establishing maximum contaminant levels (MCLs) for these chemicals.

In association with the California Air Resources Board and Dr. Norm Kado, Dr. Hsieh has developed methods for the analysis and assessment of vapor-phase mutagens in special source emissions, especially diesel engine emissions. These data are used in risk assessments of the potential health significance of this class of air contaminants.

Dr. Hsieh is also developing analytical methods and information to assess the health significance of aflatoxin M1 in milk, and fumonisin in corn. Fumonisin is a mycotoxin recently identified to be the cause of "Moldy Corn Poisoning" in horses (also called leukoencephalomalacia). Since its identification, it is now recognized as a widespread "contaminant" of corn. Its health significance to the human population is as yet unknown.

Marion G. Miller, Associate Professor

Research Program: Metabolism, Reproductive Toxicology, Fish Metabolism, and Peroxidation of Membrane Lipids.

In California, the passage of Proposition 65 and the targeting of chemicals which are known carcinogens or reproductive toxicants highlights these two important areas of public concern. As of April 1992, 378 chemicals were listed by California as cancer causing agents, 150 were listed as reproductive toxicants yet only 16 were specifically listed as male reproductive toxicants. At face value, this small number could simply reflect the fact that few compounds are toxic to the male reproductive system or, what is more likely is that this area of toxicology is poorly understood. Studies in Dr. Miller's laboratory are designed to increase understanding of male reproductive toxicology in order to develop a rational interpretation for hazard and assessment of risk. Metabolic mechanisms underlying the testicular toxicity of the nitroaromatic class of chemicals are of particular interest. These chemicals are widely used as pesticides, explosives, pharmaceuticals and chemical intermediates in industrial syntheses. A second area of interest in reproductive toxicology and encompassing a wider range of reproductive toxicants, is the development of biomarkers which signal potential for reproductive harm. Both biochemical and biophysical measurements of sperm function are being studied. The goal is to identify sperm biomarkers which signal the potential for chemical-induced alterations in fertility.

The component of Dr. Miller's research program which studies fish has developed a liver slice system to study the capacity of fish to metabolize chemicals. These liver slices offer significant advantages over the in vivo situation where experimental difficulties occur due to sampling from free swimming fish in large volumes of water. The slices can be used to describe not only metabolic and biochemical endpoints as with other in vitro approaches but also the effect of toxicants on liver pathology. Other studies in aquatic toxicology have focused on trout living in the wild which, from an environmental point of view, are more likely than farmed fish to be impacted by environmental contamination. It is known that high dietary levels of vitamin E protect farmed trout against peroxidative damage to membrane lipids. However, it was not known what the membrane levels of vitamin E were in wild fish not consuming a synthetic diet. Wild fish were found to have levels of vitamin E three times lower than the farmed fish and membrane lipids were consequently markedly more sensitive to peroxidative damage. Because of this, wild fish are likely to be more susceptible to the adverse effects of chemicals.

Robert H. Rice, Professor

Keratinocyte Culture Model for Toxic Mechanisms

The skin is our major barrier to the environment and hence is often a target for toxic substances. Dr. Rice's research involves epidermal cells cultured from the outer layer of human and rat skin. Epidermal cells are advantageous because, in contrast to epithelial cells from many anatomic sites, they can be cultured readily. With some compounds, moreover, the epidermal cells may serve as useful surrogates for other target cell types that cannot be cultured. The epidermal cells are treated with known toxins and carcinogens such as arsenic, polycyclic aromatic hydrocarbons from combustion products, heterocyclic amines from cooked meat, fungal metabolites (e.g., aflatoxins), or pesticide contaminants such as dioxins. The goals of the work include finding the mechanisms by which these agents damage the human and rat cells and comparing their relative sensitivities as targets. The results are envisioned to permit more accurate interspecies extrapolations, a major issue in animal testing. An important application involves the interactions of toxic agents, which may best be addressed using a mechanistic approach with specific target cells. We have found, for example, that dioxin (TCDD) dramatically sensitizes human epidermal cells to the toxic effects of aflatoxin and a heterocyclic amine. We are testing complex chemical mixtures to find the degree of risk presented by this phenomenon in our increasingly polluted environment.

Takayuki Shibamoto, Professor and Chairperson

Development of gas chromatographic analysis of toxic carboyl compounds including formaldehyde, acrolein, glyoxal, methylglyoxal, and malonaldehyde was one of Dr. Shibamoto's major research achievements. The method developed by Dr. Shibamoto can detect less than 1.0 pg (picogram, or 1X10-12 grams) of formaldehyde in air and be used in the range of 1 to 10,000 ppb, whereas the most commonly used NIOSH method can be used only in the range of 20 to 400 ppb. Since Dr. Shibamoto succeeded to measure the absolute amount of genotoxic malonaldehyde formed from lipid peroxidation by gas chromatography for the first time in 1988, he investigated the role of lipid peroxidation in biology and chemical systems such as in mutagenesis, aging, and carcinogenesis using this accurate method. Dr. Shibamoto isolated and identified some strong antioxidative materials such as flavones from plants. These materials showed strong inhibitory activities toward lipid peroxidation.

Dr. Shibamoto is internationally known as an expert in the Maillard reaction. (The Maillard reaction is also called the "browning reaction". It is a reaction between amino acids and sugars which results in the formation of brown products that impair food quality.) His mutagenicity studies on the Maillard reaction products were pioneer works on the biological aspects of the Maillard reaction. One of the mutagenic Maillard products N- nitrosothiazolidine was intensively studied. He has been asked to write a chapter on both the biological and chemical aspects of the Maillard reaction.

Dr. Shibamoto is also recognized as a world leader in glass capillary gas chromatography. Since Dr. Jennings retired, he is the only expert on capillary gas chromatography on this campus.

Analysis of trace water content by gas chromatography was conducted for the first time by Dr. Shibamoto.

He has continued to work on flavor chemistry. Dr. Shibamoto published several articles related to pesticide analysis while he was supervising the Trace Analysis Laboratory.

M.W. Stimmann, CE Specialist

Office of Pesticide Information and Coordination, Statewide Pesticide Coordinator

Dr. Stimmann provides the University of California Division of Agriculture and Natural Resources (DANR) with statewide coordination of all aspects of pesticide regulation, use, and safety. He has developed a program responsible for activities in pesticide applicator training, pesticide safety education, and for reviewing Division publications for conformity to current pesticide laws, rules, and regulations. As Statewide Pesticide Coordinator, he follows current developments in pesticide laws, regulations, and policies which will affect pesticide use, handling, and experimentation by members of the public and the University community, and keeps the University administration informed of these changing rules. He coordinates DANR pesticide related activities with governmental agencies, private enterprise organizations, professional societies and associations, and groups concerned with the impact of pesticides on humans and the environment.

In collaboration with the Integrated Pest Management (IPM) program, he coordinates the preparation of leaflets and other publications dealing with the safe use of pesticides, pesticide efficacy, pesticide safety, and the relationship of pesticides to IPM programs. He serves in an advisory role to state and federal agencies such as the California Environmental Protection Agency and the U.S. Environmental Protection Agency on matters of mutual interest such as groundwater protection, farmworker safety, endangered species, pesticide use and regulation.

Dr. Stimmann has developed and supervises an analytical laboratory working on applied pesticide management problems. In collaboration with Art Craigmill, Terry Prichard and Phil Osterli, he is analyzing irrigation run-off sediments for dicofol residues as part of a Soil Conservation Service collaborative study.

Barry Wilson, Professor

Also Chairperson, Department of Avian Sciences

How agricultural chemicals affect man and other animals, and how to know when people and wildlife have been exposed to them are important goals of environmental toxicology within the College of Agriculture. Dr. Barry W. Wilson is both a member of the Department of Environmental Toxicology and currently the Chairperson of the Department of Avian Sciences. His research focuses on the impact of pesticides on humans, birds, and other animals, using basic techniques in molecular, cellular, and organismic biology to study farmworkers, wild and domestic animals. He, his staff and students work closely with wildlife toxicologist, D. Michael Fry; agricultural engineer, William F. Steinke; analytical toxicologist, James N. Seiber; biochemical toxicologist, Bruce D. Hammock; veterinary pathologist, Robert J. Higgins; and Occupational Health experts such as Dr. Marc Schenker. One of his special interests has been enzymes inhibited by organophosphate and organocarbamate pesticides, especially those like acetylcholinesterase that are markers of exposure to these agricultural chemicals. Current projects include helping federal and state agencies to standardize the measurement of blood cholinesterase enzymes to better detect exposure of farmworkers to pesticides, isolating an enzyme inhibited by pesticides that cause long-term damage to the nervous system, and using muscle, liver, and nerve cells cultured from chick embryos as alternatives to studying intact animals. Recently, he and his colleagues have been working with a consortium of nut and fruit growers and chemical companies to study how pesticides sprayed in the winter in orchards affect hawks and how the technology of spraying them can be changed to reduce their drift and impact on wildlife. His long-term goal is to understand the actions of agricultural chemicals at many levels, from the molecules in the body to which they bind, the cells and tissues they damage, the animals they affect and, finally, the ecosystems they may alter. One project, in collaboration with Dr. Seiber, is to help the US Air Force to develop ways to detect if wildlife are being exposed to dangerous chemicals at Air Force sites. The findings from his laboratory are being used in the development of pesticide safety regulation guidelines of federal and state agencies. Dr. Wilson's work is supported by grower groups, the National Institutes of Health, the Environmental Protection Agency, the National Institutes of Occupational Health, and the Department of Defense.

Arthur L. Craigmill, Ph.D.
Environmental Toxicology
University of California
Davis CA 95616-8588
(530)752-2936
FAX: (530)752-3394
Email: alcraigmill@ucdavis.edu