Wendell W. Kilgore

Physiological response to organophosphate residues in field workers

The physiologic response of 21 male agricultural field workers exposed to foliage-borne Guthion residues was monitored during routine peach-thinning operations in a northern California orchard. Surveillance included daily venipuncture and urine collection to determine whole blood cholinesterase (CHE) activity and level of dialkylphosphate excretion for 3 baseline (nonexposed) and 5 normal work days. Foliage samples were obtained to measure dislodgeable and total Guthion residues. A decrease in group-mean CHE activity by 15% over the surveillance period was found. Apart from one worker who showed a consistent decrease in CHE activity, reaching a maximum of 30% below baseline at the end of the work week, daily changes in individual CHE activity were erratic. Group-mean dialkylphosphate excretion levels provided a semiquantitative indication of exposure to Guthion. Medical examination before and after the exposure period revealed an absence of clinical signs of organophosphate intoxication.

The effect of apholate and thiotepa on nucleic acid synthesis and nucleotide ratios in housefly eggs

Abstract The nucleic acid synthesis in normal viable housefly eggs and non-viable housefly eggs deposited by flies chemosterilized by apholate and thiotepa has been studied. During normal embryonic development, there is a rapid many-fold increase in DNA after an initial lag period. In the chemosterilized eggs there is almost no increase in DNA, but some accumulation of the deoxyribosidic components of the acid-soluble extract. The effect on the levels of RNA and ribosidic components of the acid-soluble extract is less apparent. The nucleotide ratios of normal housefly eggs has been determined to be similar to that reported for other insect eggs. Apholate-sterilized eggs were significantly lower in adenylic acid than normal fly-egg RNA. The RNA of the thiotepa sterilized eggs was a little lower in guanylic acid and contained an unidentified compound not present in normal egg RNA. When thiotepa P32 was the chemosterilant, all components of the isolated sodium RNA were labelled. This suggests that thiotepa may have been degraded and the resulting inorganic phosphate reincorporated into the RNA. There was no evidence of alkylated guanine in the RNA.

Determination of acute toxic effects in mice following exposure to methyl bromide

An inhalation system was designed and constructed for acute nose exposure of mice to methyl bromide. Animals were exposed for 1 h to concentrations ranging from 0.87 to 5.93 mg/l. Mice exposed to concentrations up to 1.72 mg/l did not exhibit any indication of developing a toxic response. Animals exposed to concentrations to 2.20 and 2.70 mg/l exhibited significantly decreased lung and liver weights when compared to controls. Animals exposed to concentrations above 3.50 mg/l exhibited kidney lesions. At concentrations of 3.82 mg/l and above, animals exhibited abnormal clinical signs, weight loss, and mortality. In addition, at 4.70 mg/l, a liver lesion was observed. At concentrations above 5.77 mg/l, pathological changes were observed in the color and a decreased motor coordination was evident. Methyl bromide exposures of up to 3.82 mg/l did not affect the ability of mice to recall a single-task passive-avoidance test. The 1-h LC50 of methyl bromide in mice via inhalation was determined to be 4.68 mg/l (approximately 1200 ppm). The dose-response curve was quite steep and the LC10 to LC90 range of mortality was contained within a doubling of concentration.

MITOMYCIN C: EFFECT ON RIBOSOMES OF ESCHERICHIA COLI.

Sucrose-gradient analyses of cell-free extracts of Escherichia coliB show that the sedimentation patterns are markedly affected by exposure of the cells to mitomycin C; 50S subunits are progressively degraded in the cells after 30 minutes exposure. The 30S subunits, although affected, are less sensitive to the antibiotic than the 50S subunits. Incorporation of uracil-2-C14 into the ribosomal particles by the treated cells is markedly reduced by exposure.

Worker reentry into captan-treated grape fields in California

Loader/mixers/applicators and workers engaged in thinning and harvesting grapes in the central valley of California, were monitored for exposure to captan. Urinalyses for the captan metabolite, tetrahydrophthalimide (THPI), was intended to be the biological, index for exposure to captan. Dislodgeable residues of captan and THPI on foliage and grapes were measured as well as levels found in high volume air samplers placed in the field at the time of foliage sampling. Loader/mixer/ applicators were monitored following an application of a 10% dust and a wettable powder (W.P.) formulation just prior to thinning operations, and again at harvest with a W.P. formulation. Loader/ mixer/applicators were also monitored with and without respiratory protection with each treatment. The half-life of captan for the dust application was 12.8 days, and 19.6 days for W.P. Tetrahydrophthalimide levels were very low in all the field and clothing samples and were not a significant factor in worker exposure. Levels of captan in the air during the loading/mixing operation were higher. Although there were exceptions, gloves contained the highest levels of residues in the loader/mixer/applicators and the field workers. The relative levels found on the patches were reflective of the work habits of the workers. The applicators of the 10% dust had the highest captan levels in the personnel air samplers and on their mask or respirator pads. The results from the urine analysis, although THPI was found, showed no significant differences in trends between the pre- and post-exposure samples except possibly the individual who wore the respirator during the dusting operation. Pre- and post-exposure urine samples of field workers engaged in the thinning and harvesting operation showed no significant differences except workers engaged in the dusted plot. Dislodgeable foliage levels and glove residues from workers are used to measure potential dermal exposure, and since these two parameters were lowest in the dusted plots coupled with the same or slightly higher levels found in the high volume air samples in the dusted plot, they support the importance of investigating inhalation as a primary source of exposure to captan. Estimated dermal exposure in mg/person in relation to each pound of captan applied by loader/mixer/applicators was highest with those engaged in the dusting operation; the applicators during the harvest operation had much lower levels compared to the loader/ mixer/applicators during the thinning operation.

Epidemiologic study of physiological effects in usual and volunteer citrus workers from organophosphate pesticide residues at reentry

Biological parameters associated with organophosphate (OP) pesticide exposure were evaluated in a study of citrus harvesters. Changes in these parameters related to environmental residues of cholinesterase (ChE) inhibiting pesticides were studied. Further, it was determined whether usual and volunteer workers differed in their biochemical parameters after exposure to pesticide residues during field operations. Urine metabolite findings for usual farm workers showed that some exposure to OP pesticides had occurred. Too few workers were available during the reentry stage of the field study to evaluate the effect of this exposure on blood ChE. Baseline (nonexposure) acetylcholinesterase (AChE) and plasma cholinesterase (PChE) activities were significantly higher in usual (Mexican American) workers than in volunteer workers (student volunteers). Student volunteers in the test citrus grove showed statistically significant declines in PChE during the exposure period, yet changes in AChE activity, urine metabolites, and residue levels were very small. The implications of these findings are discussed in light of current reentry standards as well as future epidemiologic studies on reentry research.

Tissue levels of glutathione following acute inhalation of 1,3‐dichloropropene

Rats were exposed by inhalation to 1,3-dichloropropene (DCP) to assess the relationship between DCP exposure concentration and tissue levels of reduced glutathione (GSH). Animals were exposed for 1 h in a dynamic, nose-only system. GSH content, indicative of DCP metabolism, was measured in heart, kidney, liver, lung, nasal mucosa, and testes. A decrease in nasal GSH content was first seen at 5 ppm DCP and followed an exposure concentration-dependent curve. Exposure to concentrations above 305 ppm DCP reduced the level of liver GSH in an exposure concentration-dependent manner. Although depressed, lung GSH content remained relatively constant at approximately 75% of control following concentrations of up to 955 ppm DCP. Significant decreases in GSH content were observed in heart, liver, and testes only at 1716 ppm. Additional measurements were taken to investigate DCP distribution and potential indicators of acute toxicity. DCP was not present in the blood of animals 2 h after exposure to 955 ppm DCP or less. Serum lactate dehydrogenase activity was affected only at the highest exposure concentration, 1716 ppm DCP. Lung weight, measured at 2 and 6 h after exposure, did not differ from control for any of the exposure levels. This information demonstrated the importance of nasal tissue GSH in the metabolism of at least low levels of DCP. It also suggests the complexities involved with in vivo defence against inhaled DCP.

Protein synthesis by ribosomes from fertilized and unfertilized eggs of houseflies, Musca domestica

Abstract The ribosomes from unfertilized and fertilized housefly eggs have been isolated and their ability to initiate protein synthesis in a cell-free system has been investigated. There is a greater proportion of polymeric forms in the ribosomes from fertilized eggs, and these have a greater capacity to initiate protein synthesis.

Mercapturic acid excretion by rats following inhalation exposure to 1,3-dichloropropene.

Rats were exposed to 1,3-dichloropropene (DCP), a commonly used agricultural nematicide, by inhalation to assess the relationship between DCP concentration and the urinary excretion of the mercapturic acid of cis-DCP (3C-NAC). The nose-only exposure system that was used for simultaneously exposing up to four rodents is described. This apparatus provided for generation and monitoring of relative humidity and test vapor concentration. Animals were exposed for 1 hr to concentrations of up to 789 ppm DCP. Urine was collected for 24 hr after exposure. The quantity of 3C-NAC contained in the urine collections exhibited an exposure concentration-dependent increase from 0 to 284 ppm DCP. However, the amount of 3C-NAC was no greater for animals exposed to 398 or 789 ppm DCP than for animals exposed to 284 ppm DCP.

Toxicities and description of some toxaphene fractions: Isolation and identification of a highly toxic component

Toxaphene was separated into 13 fractions and the toxicity of each fraction was determined. The acute toxicities (LD50) to houseflies (topical in acetone) ranged from 21 to greater than 246 mg/kg (toxaphene LD50 = 33 mg/kg) and the relative toxicities ranged from 0.6 to greater than 7.5. A similar pattern was found in mice when the toxicities of several fractions were determined. The acute toxicities (LD50, ip injection in dimethyl sulfoxide) in mice ranged from 20 to 67 mg/kg (toxaphene LD50 = 33 mg/kg) for the fractions tested. The most toxic fraction was further separated into six subfractions and their toxicities (housefly LD50) were found to range from 10 to 74 mg/kg. The most toxic subfraction appeared to be an almost pure compound and was purified for further identification. It was found to be identical to a previously reported highly toxic C10H10Cl8 mixture of predominantly two components. The components were reported to be 2,2,5-endo,6-exo, 8,8,9,10-octachlorobornane and 2,2,5-endo,6-exo,8,9,9,10-octachlorobornane. This highly toxic mixture has now been isolated independently by three research teams using different separation schemes.