Serum proteins and work habits in a group of farm-workers exposed to EBDCs.

BACKGROUND: Study of the association between genetic variability and individual susceptibility can help to characterize occupational or environmental risks due to xenobiotics. AIM: This study evaluates the influence of genetic components and environmental factors in relation to pesticide exposure. SUBJECTS AND METHODS: The study population consisted of 37 non-occupationally exposed workers and 74 farm-workers exposed to pesticide. Exposure was assessed through the measurement of urine concentration of ethylenethiourea (ETU). Genetic differences in drug metabolism were detected by a qualitative variability in serum proteins. The environmental factors were recorded by using a questionnaire. RESULTS: The results show a difference between ETU levels in farm-workers and in non-occupationally exposed workers. In the non-exposed group a relationship between ETU urinary concentration and lifestyle habits is present. In farm-workers ETU urinary concentration is less correlated with lifestyle habits, but is associated, rather, with their work. In the exposed individuals the serum protein analyses show a possible link between ETU urinary concentration and the polymorphism of group-specific component (Gc). CONCLUSIONS: The association between Gc polymorphism and ETU urinary concentration of subjects exposed to EBDCs could be due to the immunological function of Gc and the effects on the immune system of EBDCs.

Reference values for ethylenethiourea in urine in Northern Italy: results of a pilot study.

This study was carried out to define reference values for urinary ethylenethiourea (ETU) in the Northern Italy population and to identify the sources of exposure. Ninety-five healthy subjects were selected. A spot urine sample was collected in the morning, and analyzed using GC/MS in the EI/SIM mode. Thirty-nine subjects showed urinary ETU concentrations lower than the limit of detection (LOD, 0.4 microg/g creatinine), and the remainders ETU concentrations ranging from 0.5 to 11.6 microg/g creatinine. No correlation was shown between smoke or alcohol intake and urinary ETU concentrations. Based on data on ethylene-bis-dithiocarbamate (EBDC) concentrations in food, we estimated a total EBDCs intake of 31.7-50.1 microg/day. These values are largely below the ADIs, but explain the presence of small amounts of ETU in the urine samples we have analyzed. Finally, it was estimated that the mean ETU in urine in the Italian general population is 0.6-0.8 microg/g creatinine, with a 95th percentile of 4.5-5.0 microg/g creatinine. These values can be used as reference, to compare the results of biological monitoring activities carried out on EBDCs occupationally and environmentally exposed populations.

Correlation between blood ethylenethiourea and thyroid gland disorders among banana plantation workers in the Philippines.

Ethylenebisdithiocarbamates (EBDCs) are metabolized into ethylenethiourea (ETU), a possible human carcinogen and an antithyroid compound. In this study our goal was to correlate ETU levels with the incidence of thyroid gland disorders among banana plantation workers exposed to EBDC. We randomly selected 57 directly exposed workers and 31 indirectly exposed workers from four banana plantations and 43 workers from an organic farm; all subjects underwent complete medical examinations and laboratory tests. Results showed a higher mean thyroid-stimulating hormone measurement among exposed workers compared with the control group, although the levels were well within normal range. Nine of the exposed farmers had abnormal thyroid ultrasound findings, consisting mostly of solitary nodules, compared with three among the control group. Analysis of variance showed significantly different blood ETU levels among the directly exposed, indirectly exposed, and control groups (p < 0.001), but ETU levels in urine were not significantly different (p = 0.10). Environmental ETU levels were below the U.S. Environmental Protection Agency remediation levels. Among farmers with solitary thyroid nodules, we found a very good direct correlation between the size of the nodule and blood ETU level. In this study we showed that blood ETU is a more reliable biomarker for EBDC exposure than urinary ETU; therefore, the determination of blood ETU should be part of medical surveillance efforts among workers exposed to EBDC to detect occurrences of thyroid gland disorders.

Ethylenebisdithiocarbamates and ethylenethiourea: possible human health hazards.

Humans are exposed to ethylenebisdithiocarbamates (EBDCs) from environmental sources. Exposure to EBDCs is chronic for workers in a variety of industries, where EBDCs are used for their properties as slimicides, vulcanization accelerators, antioxidants, and scavengers in waste-water treatment. EBDCs, and particularly the EBDC metabolite ethylenethiourea, have clearly defined, important toxic effects in various animal species, and there is reason to suspect they are carcinogenic in humans. In the absence of definitive information regarding human risk, further studies need to be done. In the interim, regular surveillance of workers with high levels of exposure to EBDCs, with specific attention to markers of thyroid and hepatic pathology, should be considered.

[Evaluation of urinary excretion of ethylenethiourea in subjects occupationally and non-occupationally exposed to ethylenebis(dithiocarbamates)]. / Valutazione dell'escrezione urinaria di etilentiourea in soggetti professionalmente e non professionalmente esposti ad etilenbisditiocarbammati.

Ethylenebisdithiorcabamate (EBDC) fungicides are broken down metabolically and in the environment to ethylenethiourea (ETU), a suspected carcinogen. Urinary ETU was assayed in control groups and subjects occupationaly exposed to EBDC and was found to be an excellent indicator of exposure both to ETU and EBDC. Correct use of protective clothing greatly reduced exposure and urinary excretion of ETU. ETU was excreted, albeit in low concentrations, in a high percentage (91% and 30%) of subjects in both control groups, demonstrating its utility as an indicator of widespread EBDC contamination.

Drinking water guideline for ethylene thiourea, a metabolite of ethylene bisdithiocarbamate fungicides.

The ethylene bisdithiocarbamate fungicides are the most heavily used pesticides in Maine. Ethylene thiourea (ETU) is a metabolite and environmental decomposition product of these compounds, is highly water soluble, and has been detected in groundwater in the state. ETU is a recognized animal carcinogen and teratogen. When administered in the diet, ETU produced a significant increase in thyroid carcinomas in rats in two studies. Two strains of mice fed ETU in the diet developed an increased incidence of hepatomas and a slight increase in lymphomas. Application of the linearized multistage model resulted in virtually safe doses (10(-5) lifetime cancer risk) of 0.25 to 1.6 micrograms/kg/day. The major teratologic effect has been the development of hydrocephalus and other CNS defects postnatally, resulting in a high mortality rate among the offspring. The NOEL for this effect was 5 mg/kg in a single oral dose. Retarded parietal ossification was observed at 5 mg/kg/day. Serious nononcogenic thyroid effects, such as goiter, decreased 131I uptake, and reduced thyroxine production, have been observed. Thyroid hyperplasia was produced at doses as low as 0.3 mg/kg/day ETU ingested in the diet. Based on protection against thyroid and/or liver tumors and alteration in thyroid function, the recommended Drinking Water Guideline for ETU is determined to be 3 ppb. This will also provide protection against developmental effects, since these occur at doses that are one to two orders of magnitude higher.

Studies on the mechanism of nabam- and zineb-induced inhibition of the hepatic microsomal monooxygenases of the male rat.

In vitro effects of the ethylene bis-dithiocarbamate fungicides, nabam and zineb, on the hepatic microsomal monooxygenases of male rats were examined. Incubation of nabam and zineb with hepatic microsomes, without NADPH, leads to an inhibition of the metabolism of aminopyrine and aniline and to a denaturation of cytochrome P-450 into cytochrome P-420; in addition nabam causes the destruction of cytochrome P-450. Addition of NADPH into the incubation medium increases the inhibition of the monooxygenases, principally the inhibition of the metabolism of aniline induced by nabam. We studied the in vitro effects of three of the chief breakdown products of these fungicides: ethylene bis-isothiocyanate sulfide (EBIS), ethylene thiourea (ETU), and carbon disulfide (CS2). EBIS appears to be the only metabolite affecting directly (without NADPH) the hepatic monooxygenases activity. EBIS accounted partly for nabam-induced inhibition of the hepatic microsomal monooxygenases. The data suggest that the decrease of monooxygenases activity seen on incubation of nabam with hepatic microsomes may be due to the denaturation and destruction of cytochrome P-450 resulting from covalent binding of the compounds with cysteine sulfhydryl groups in cytochrome P-450. Inhibition of monooxygenase activity induced by zineb seems to be due to the reaction with the sulfhydryl groups of cytochrome P-450 and to another mechanism, probably related to its lipophilic character.

Testing of the fungicide maneb for carcinogenicity in two populations of the European crested newt.

The carcinogenic effects of the fungicide manganese ethylenebisdithiocarbamate (maneb) have been investigated in 2 populations of adult crested newt, which have different prevalences of spontaneous melanoma. Animals were exposed percutaneously to a 5 ppm solution of maneb 4 days a week for 37 weeks. No differences in tumor incidence were found between control and maneb-treated animals of either population. Most of the control and treated animals from Settala (Milan) died within 7 months because of the development of widely disseminated melanomas. Tumor incidence was 94% in controls and 98% in maneb-treated newts. In the population from Bagnaia (Perugia) the incidences of melanoma were 7% and 2%, respectively.