Vol. 5 No. 3 September, 1985


Table of Contents

I. Introduction
II. Outbreak of Phototoxic Dermatitis from Limes - Maryland III.
Neurologic Findings Among Workers Exposed to Fenthion in a
Veterinary Hospital - Georgia
IV. An Update on 1,3-Dichloropropene
V. People Don't Buckle up: Low Risks for Each Trip

I. Introduction

The last three months have been filled with toxicity emergencies that have been widely publicized. The biggest of course is the finding of metabolites of aldicarb in watermelons and the association of the residue with widespread human illness. Since the complete picture of this situation has not yet been developed, I will wait to address it in a future newsletter. This episode has helped to point out the complexity of addressing toxicity information needs of the public, and ways in which the University can help fulfill these needs in a timely manner.

On another front, The Task Force on Hazardous Agricultural Chemicals in the Environment (HACE) held a workshop in early July to develop a list of current and future research and extension needs for the state, and to relate these needs to programs within the university that can help to address these needs. The participants in the workshop included representatives from Berkeley, Riverside, Davis, Lawrence Livermore Laboratory, Lawrence Berkeley Laboratory, and state agencies. The workshop participants divided into four groups to address the following subject areas: Environmental Fate and Chemistry (emphasis on groundwater pollution), Toxicology, Agricultural Waste Disposal (emphasis on pesticide wastes), and Source Management (ways to reduce waste production). The report developed from this workshop will be published as a special edition of this newsletter in the near future. This issue once again contains tidbits taken from a variety of sources as well as a guest article from Mr. John Lowe.

The latest version of the Pesticide Toxicity Profiles (PTP's) that have been developed for use on the county office CompuPro's will be distributed to those county offices that requested copies by the end of September. This version contains basic toxicity and environmental fate information on over 190 chemicals used in agriculture. The PTP's are written as Wordstar files that can be printed out as needed. Feedback from county users of the PTP's would be greatly appreciated.

A belated correction of information included in Volume 5 Number 2 is in order. The second article in that issue was titled Poisonings: Drugs are No. 1 Cause, and was excerpted from a USA TODAY, Wednesday, October 10, 1984. The paragraph that is in error read as follows: "Eating the leaves of toxic house plants led to 22,326 poisonings. No deaths were reported. Most dangerous: philodendron, dieffenbachia and poinsettia." Dr. Art McCain pointed out that this statement is in error in that the poinsettia has not been found to be a toxic plant. My thanks to him for noticing this (it's nice to know someone is reading this newsletter). My interpretation of what the author was trying to say is that these three plants are the ones most often mentioned in calls to poison control centers, not necessarily that they are the most dangerous.

I will be away from the office on business and vacation for the last half of August and all of September. If you have any questions relating to the Extension Toxicology Program, or need some information please call the Extension Toxicology Secretary, Sandy Ogletree and she will help you.

II. Outbreak_of_Phototoxic_Dermatitis_from_Limes_-_Maryland

On August 8, 1984, the Office of Disease Control and Epidemiology, Maryland Department of Health and Mental Hygiene, was notified by a nurse at a day camp in Owings Mills, Maryland, of a rash illness reported among 12 children during the previous week. The rash, confined to the dorsa of the hands and extensor and flexor surfaces of the forearms and in the form of blotches, speckles, and streaks, was macular, hyperpigmented, and nonpruritic. No other signs or symptoms were noted. Dermatologists diagnosed the rash as a phototoxic contact dermatitis. Investigation disclosed that limes used in an art class to make pomander balls were incriminated as the cause of the rash.

Editorial Note: Photosensitivity of the skin refers to an abnormal reaction of the skin to light. This abnormal reaction results from exposure to certain therapeutic or chemical agents. Exposure may occur when the offending agent is either ingested or applied topically. The reaction occurs only after an exposed individual is subjected to ultraviolet or visible light. In most cases, the offending agents do not act as contact irritants by themselves; they are harmless to skin in the absence of exposure to light.

Photosensitivity reactions are classified as either photoallergic or phototoxic. Photoallergy involves the immune system. The offending agent, acting as a hapten, absorbs radiation, becomes activated, and reacts with protein(s) within the skin to form an antigen(s). This photoantigen is immunologically processed and manifests itself as an ordinary delayed hypersensitivity response. The patient with photoallergy has eczematous or papulovesicular eruptions.

In contrast to photoallergy, phototoxicity does not involve the immune system. Most often, phototoxic reactions can be produced in an individual if he or she is exposed to both an appropriate concentration of the offending agent and sufficient light energy of the correct wavelength. The patient with phototoxicity has an exaggerated sunburn reaction, with or without vesicles, edema, and hyperpigmentation. The reaction occurs within 5-18 hours after the patient is exposed to light; it is most intense 36-72 hours after exposure.

Furocoumarins are heterocyclic aromatic compounds naturally found in the skin of citrus fruits, including limes. Psoralen, a compound resembling the naturally occurring furocoumarins, has been shown to produce photosensitivity reactions.

In all cases of photosensitivity, rapid diagnosis and identification of the offending agent are fundamental in effecting control. In photoallergy, cross-sensitization to closely related photoantigens can occur: the patient should be alerted to this possibility. In phototoxicity, the severity of symptoms depends on the concentration of exposures, and a variety of clinical presentations may be observed within an exposed group. Further measures call for eliminating, or at least reducing, exposure to the offending agent. Exposure to sunlight should be minimized, sunscreens should be used, and patient education should be emphasized.

MMWR, Vol. 34/No. 30, August 2, 1985

III. Neurologic_Findings_Among_Workers_Exposed_to Fenthion_in_a_Veterinary_Hospital_-_Georgia

In July 1983, a neurologist in Georgia saw a patient who complained of shooting pains, muscle weakness, and numbness. The patient worked at a veterinary hospital (hospital A).

Medical examinations revealed that two additional workers at hospital A experienced multiple shooting pains, muscle weakness, back pain, and numbness; another had experienced occasional "shooting pain" in the back, and a fourth complained of rare numbness and tingling of the hands and feet at night. Results of tests of plasma and red blood cell cholinesterase activity were within the normal range for all workers tested, including the most severely ill worker.

Investigators noted 22 different preparations of insecticide dips, shampoos, pills, powders, and sprays used in or dispensed by hospital A. These products contained 12 types of pesticides. Employees took no special precautions to avoid skin contact with these materials, except one animal groomer who wore gloves and a dust mask when working with certain dips.

The telephone survey of three other veterinary hospitals in the area revealed no reports of similar illnesses among 20 employees. However, a difference in work practices was identified; in hospital A, an organophosphate insecticide, fenthion, was frequently used. In contrast, fenthion was used infrequently or not at all at the other hospitals surveyed. No other notable differences in work practices were identified. In hospital A, a 20% solution of fenthion was routinely applied topically to dogs in the hospital to control infestation with fleas. Investigators determined that affected workers frequently came in heavy contact with fenthion.

The investigators recommended that use of fenthion be discontinued and alternative insecticides be selected. They also recommended limiting skin contact with all pesticides as much as possible. Since discontinuing exposure to fenthion, both individuals who were most severely affected have gradually improved.

Editorial Note: The pesticide, fenthion (0,0-dimethyl-0-[4- (methylthio)-m-tolyl] phosphorothiolate), is readily absorbed through the skin; it is highly fat soluble and has prolonged biologic effects. In very limited studies, neurotoxicity has been demonstrated in hens.

In humans and in experimental animals, chronic exposure to organophosphates has been shown to cause various forms of nerve damage. Organophosphate-induced delayed neuropathy usually occurs 8-14 days after exposure to organophosphate compounds. The mixed sensory-motor neuropathy usually begins in the legs, first causing burning or tingling sensations, then weakness of the lower legs and feet. The thighs and arms also become involved. Severe cases proceed to complete paralysis, impaired respiration, and death. Confusion, headache, disorientation, and altered mental and emotional states have also been reported. The nerve damage of organophosphate-induced delayed neuropathy is usually permanent. Although organophosphate-induced delayed neuropathy has been reported after exposure to many compounds containing phosphorus-esters, none of the compounds to which workers were exposed in hospital A are commonly recognized as causing it. Therefore, because of the above investigation, it would appear prudent to add fenthion to the list of agents thought capable of producing this syndrome.

An estimated 30,000 veterinarians are in private practice in the United States, and they employ an additional 45,000 support personnel. It is not known how many use fenthion or other organophosphate insecticides in the manner described here. However, because of the apparent association of symptoms specifically with fenthion, and because of scientific information currently available on the neurotoxicity of other organophosphates, NIOSH reiterates its previous recommendation that skin contact with all pesticides, including fenthion, be limited as much as possible.

MMWR, Vol. 34/No. 26, July 5, 1985

IV. An_Update_on_1,3-Dichloropropene

Written by John Lowe
Industrial Hygiene Consultant

1,3-Dichloropropene (1,3-D) has become an extremely popular replacement for DBCP, with the use increasing many-fold in California since 1977. As with other halogenated hydrocarbons used in agriculture (DBCP, EDB and 1,2-dichloropropane), the potential health hazards associated with 1,3-D must be considered.

Laboratory studies indicate that 1,3-D has carcinogenic and mutagenic potential. Tests with the Ames assay have shown it to be mutagenic in three bacterial strains. 1,3-D is carcinogenic in lifetime exposure studies in mice by subcutaneous injection, however not by skin painting. Based on this evidence, the National Toxicology Program (NTP) selected 1,3-D as a candidate for a cancer bioassay. In the NTP study, 1,3-D, administered by gavage three days a week for 104 weeks, was considered carcinogenic in male and female rats and female mice, however, the study report concluded that the experiment on male mice was an inadequate study of carcinogenicity due to reduced survival in the control group. The bioassay was audited by the NTP Board of Scientific Counselors for possible deficiencies in the experimental methods. Their conclusion was that the deficiencies were well documented and did not materially affect the carcinogenicity findings.

The assessment of carcinogenicity is complicated by the presence of impurities and additives in fumigants containing 1,3- D, including dichloropropene isomers, 1,2-dichloropropane (1,2-D) and epichlorohydrin. Epichlorohydrin has shown evidence of carcinogenicity in animal bioassays; the 1,3-D tested in the NTP bioassay contained 1% epichlorohydrin. 1,2-D is considered carcinogenic based on another NTP bioassay, although it has less mutagenic activity after purification with column chromatography. The impurities were tested separately and found to be mutagenic. From this, the investigators suggested that the mutagenicity of 1,3-D is due to impurities associated with it. They concluded that the effects of storage on formation of impurities is not known, nor is it known if 1,3-D can be purified commercially.

Recently, two physicians have published a report of three patients being treated for hematologic malignancies (blood cancers). Two were firefighters cleaning up a road spill of 1,3- D in 1973, the other a pesticide applicator with repeated dermal and inhalation exposure to 1,3-D. Reportedly, his clothes carried such a strong chemical odor that his wife laundered his work clothes separately. All three died of their cancers within 6 years following exposure. Because of the similarities in the disease progressions, the authors suggested that the physician note 1,3-D exposure in a patient's medical history. The health status is being followed for seven firefighters, also in the spill response team. Reportedly, none have shown any signs of cancer. The NTP cancer bioassay did not report any significant occurrence of hematologic malignancies.

The Worker Health and Safety Unit of the California Department of Food and Agriculture conducted three exposure studies (covering from 1979 to 1983) of tractor drivers applying 1,3-D. In the earlier studies, drivers inhalation exposures were monitored with air samples for 2 hours a day; average potential inhalation exposure concentrations were 0.4 ppm. In 1983, exposure concentrations were measured as 8-hour time-weighted- averages (TWA) with portions of the workday not devoted to soil fumigation assumed to be zero exposure. The average TWA exposure concentration was 0.7 ppm, although potential inhalation exposures of nearly 4 ppm were measured. These values do not include potential exposures in equipment yards or from performing bulk transfer operations. The American Conference of Governmental Industrial Hygienists (ACGIH) recommends a Threshold Limit Value (TLV) of 1 ppm for 1,3-D, based on an 8-hour TWA exposure. (TLVs represent air concentrations to which is believed that nearly all workers may be repeatedly exposed day after day without adverse effect). The TLV is based on 9-month inhalation studies in several animal species, in which a no- effect level of 1 ppm was achieved, however, it had been recommended prior to findings of carcinogenicity for 1,3-D.

The transferral of fumigant from a supply tank to the tractor in the field was considered as a source of peak exposure concentrations. These concentrations were monitored with short- duration air samples. Most samples contained from 1 to 5 ppm, though 42 ppm was detected during a closed-system accident releasing approximately 2 liters of liquid fumigant. Small traces of 1,3-D (less than 20 micrograms) were detected on the hands of drivers, however the methods of measuring skin exposure may underestimate exposure from this route. Appropriate methods for measuring skin exposure to volatile fumigants await further development. In two cases of twenty fumigant applications monitored in 1983, hand exposures to the point of liquid runoff were observed to occur. One was a fieldman calibrating an application rig, while the other was a driver cleaning a filter in a delivery line. Coincidentally, gloves were not worn in either case.

1,3-D is rapidly detoxified in rats and man by conjugation with glutathione and excretion in the urine. A method has been developed for measuring the 1,3-D metabolite in urine, and in one study with tractor drivers, the data showed a good correlation between metabolite excretion and 1,3-D concentrations measured in air samples.

The potential for 1,3-D to contaminate groundwater has been assessed in three separate studies. In two studies by the Worker Health and Safety Unit (1979 and 1981), 1,3-D was not detected in well water samples down to 0.1 ppb. In 1983, the Water Resources Control Board sampled well water for 1,2-D and 1,3-D. 1,2-D was found in some samples in concentrations ranging from 0.2 to 25 ppb, though 1,3-D was not detected. A breakdown product of 1,3-D in soil (3-chloroallyl alcohol) and 1,2-D were detected in monitoring wells at an abandoned pesticide storage site; 1,2-D concentrations up to 1.2 ppm and chloroallyl alcohol concentrations up to 1.4 ppm were detected at this particular site. Based upon these findings, soil fumigants containing 1,2-D (predominantly DDR) were voluntarily removed from the California market. Currently, CDFA is proposing regulations to limit 1,2-D content in fumigants to 0.5 percent.

Recently, a report from the State Assembly Office of Research stated that 1,3-D was found in a well in Santa Clara by the Department of Health Services (DHS). However, a DHS scientist conducting the study stated that a resample from this well contained no detectable residues. He suggested laboratory error as a cause for the initial result.

V. People_Don't_Buckle_Up:__Low_Risks_for_Each_Trip

A recent feature from the American Psychological Association quotes psychologist Paul Slovic, PhD, of Decision Research in Eugene, Oregon, as saying most Americans don't wear their seat belts because they perceive of the risk they are taking only one car trip at a time.

Indeed, says APA, the chances of being killed in an accident on any one auto trip are very small: only about one in four million. The chances of being in a disabling accident are only one in 100,000.

However, the risks involved in the habit of not buckling up over a lifetime are quite different. Over a lifetime, with an average of 50,000 auto trips, a person has one chance in a hundred of being killed in an accident and a one in three chance of being seriously injured.

Slovic says that he supports the adoption of the state seat belt laws, which have now been enacted in five states, because, "It's a hopeless task to try to motivate people to voluntarily wear seat belts".--The Nations's Health, official newspaper of the American Public Health Association, May-June 1985.

University of Florida Cooperative Extension, Veterinary Medicine Newsletter, July 1985

Arthur L. Craigmill
Toxicology Specialist
U.C. Davis