Environmental and biological monitoring of non-occupational exposure to 1,3-dichloropropene

Voluntary bystanders, simulating a situation of non-occupational exposure to Z- and E-1,3-dichloropropene (Z- and E-DCP), were exposed during field application of this nematocide in the Dutch flower-bulb culture. Environmental monitoring revealed that mean respiratory exposure concentrations of Z- and E-DCP varied from non-detectable levels to 1.12 mg/m3 8-h time-weighted average (TWA) for Z-DCP and to 0.91 mg/m3 8-h TWA for E-DCP. Biological monitoring was executed by determining urinary mercapturic acid metabolites of Z- and E-DCP according to a method recently validated in occupationally exposed applicators. A linear relationship between respiratory exposure to Z- and E-DCP and the urinary excretion of both mercapturic acids was observed in bystanders. Dermal uptake did not contribute significantly to the internal dose of Z- or E-DCP. The urinary mercapturic acid of Z-DCP was a more sensitive parameter for the detection of exposure than was respiratory air monitoring. In future studies it would be worthwhile to determine the extent of exposure of real bystanders to DCP on the basis of urinary mercapturic acid excretion

Identification and quantitative determination of a carboxylic and a mercapturic acid metabolite of etridiazole in urine of rat and man. Potential tools for biological monitoring

Etridiazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, was orally administered to rats and human volunteers. Two metabolites of etridiazole were synthesized: 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid (ET-CA) and N-acetyl-S-(5-ethoxy-1,2,4-thiadiazol-3-yl-methyl)-L-cysteine (ET-MA). Selective and sensitive analytical procedures to determine etridiazole, the carboxylic acid ET-CA and the mercapturic acid ET-MA in urine were developed. The detection limit of etridiazole, applying GC with nitrogen selective detection (GC-NPD), was 36 micrograms/l urine (CV = 15.4%, n = 3). The detection limit of ET-CA, applying GC with sulphur selective detection (GC-FPD), was 100 micrograms/l urine (CV = 9.8%, n = 3). In urine of rats orally treated with etridiazole, ET-CA and ET-MA were identified as metabolites of etridiazole, whereas in urine of humans given oral etridiazole, only ET-CA was identified. Unmetabolized etridiazole was excreted for less than 0.1% of the administered dose in rats. ET-CA, however, accounted for 22 +/- 9% of the administered dose of etridiazole in rats and for 13 +/- 6% in humans. ET-MA appeared to be a minor urinary metabolite of etridiazole. ET-CA is proposed as a possible biomarker for the biological monitoring of etridiazole

Mercapturic acids, protein adducts, and DNA adducts as biomarkers of electrophilic chemicals

The possibilities and limitations of using mercapturic acids and protein and DNA adducts for the assessment of internal and effective doses of electrophilic chemicals are reviewed. Electrophilic chemicals may be considered as potential mutagens and/or carcinogens. Mercapturic acids and protein and DNA adducts are considered as selective biomarkers because they reflect the chemical structure of the parent compounds or the reactive electrophilic metabolites formed during biotransformation. In general, mercapturic acids are used for the assessment of recent exposure, whereas protein and DNA adducts are used for the assessment of semichronic or chronic exposure. 2-Hydroxyethyl mercapturic acid has been shown to be the urinary excretion product of five different reactive electrophilic intermediates. Classification of these electrophiles according to their acid-base properties might provide a tool to predict their preference to conjugate with either glutathione and proteins or with DNA. Constant relationships appear to exist in the cases of 1,2-dibromoethane and ethylene oxide between urinary mercapturic acid excretion and DNA and protein adduct concentrations. This suggests that mercapturic acids in some cases may also play a role as a biomarker of effective dose. It is concluded that simultaneous determination of mercapturic acids, protein and DNA adducts, and other metabolites can greatly increase our knowledge of the specific roles these biomarkers play in internal and effective dose assessment. If the relationship between exposure and effect is known, similar to protein and DNA adducts, mercapturic acids might also be helpful in (individual) health risk assessment

N-acetyl-S-(2-hydroxyethyl)-L-cysteine as a potential tool in biological monitoring studies?: A critical evaluation of possibilities and limitations

In mammalian species, including man, N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-HEMA) is a common urinary metabolite of a large number of structurally different xenobiotic chemicals. It is a common urinary end product of glutathione pathway metabolism of a variety of chemicals possessing electrophilic properties and, in most cases, also a genotoxic potential. Five different chemically reactive intermediates, with different electrophilic properties, may be involved in the formation of 2-HEMA. An inventory of chemicals known to lead to the formation of 2-HEMA, or based on their chemical structure expected to do so, is presented. Furthermore, an attempt is made to evaluate the possibilities and limitations in terms of the potential use of urinary 2-HEMA as a tool in biomonitoring studies. Two other related, sulfur-containing urinary metabolites, i.e. N-acetyl-(S-carboxymethyl)-L-cysteine and thio-diacetic acid, are proposed as possible alternatives to urinary 2-HEMA. It is suggested that 2-HEMA might be seen as a potentially useful and sensitive signal parameter for the assessment of exposure of animals and man to a variety of electrophilic and therefore potentially toxic xenobiotic chemicals

Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid, urinary metabolites of the fungicide captan, in rats and humans

Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 micrograms/l for THPI and 110 micrograms/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48-h cumulative urinary excretion of THPI of 1%-2% and 3%-9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non-exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan

Inhalation exposure to 1,3-dichloropropene in the Dutch flower-bulb culture. Part II. Biological monitoring by measurement of urinary excretion of two mercapturic acid metabolites

A biological monitoring study was carried out in the Dutch flower-bulb culture to determine the relationship between respiratory occupational exposure to Z- and E-1,3-dichloropropene (Z- and E-DCP) and urinary excretion of two mercapturic acid metabolites, N-acetyl-S-(Z- and E-3-chloropropenyl-2)-L- cysteine (Z- and E-DCP-MA). Urinary excretion of Z- and E-DCP-MA, either based on excretion rates or on creatinine excretion, followed first order elimination kinetics after exposure. Urinary half-lives of elimination were 5.0 +/- 1.2 hr for Z-DCP-MA and 4.7 +/- 1.3 hr for E-DCP-MA and were not statistically significantly different. Calculated coefficients of variation indicated that the half-lives of elimination of Z- and E-DCP-MA were quite consistent inter- and intra-individually. Strong correlations (r greater than or equal to 0.93) were observed between respiratory 8-hr time weighted average (TWA) exposure to Z- and E-DCP and complete cumulative urinary excretion of Z- and E-DCP-MA. Z-DCP yielded three times more mercapturic acid than E-DCP, probably due to differences in metabolism. Z- and E-DCP were excreted 45 and 14% as their respective mercapturic acid metabolites. A respiratory 8-hr TWA exposure to the Dutch occupational exposure limit of 5 mg.m-3 DCP would result in a complete cumulative excretion of 14.4 mg (95% confidence interval: 11.7-17.0 mg) Z-DCP-MA and 3.2 mg (95% confidence interval: 2.3-4.1 mg) E-DCP-MA

Determinantes de salud oral en población de 12 años Oral health determinant in 12 year-old population

Objetivo: Determinar la prevalencia de caries y factores asociados con historia de caries y autopercepción de salud oral de escolares de 12 años de establecimientos educacionales municipalizados, comparando población urbana y rural en la Región del Maule, Chile. Material y Método: Estudio transversal en una muestra por conveniencia de 285 escolares de cuatro comunas de la Región. El examen clínico fue realizado por un examinador calibrado. Se midieron variables demográficas, índice COPD, Índice de higiene oral, autopercepción del estado de salud oral y última visita al dentista. Resultados: La prevalencia de caries fue 63.9%, sin diferencias significativa por sexo y área residencia. Los niños tienen 3.17 (95% IC 1.62-6.20) veces más riesgo de tener un COPD=0 en relación a las niñas; la higiene oral también se asoció a un COPD=0 (OR=0.24 95% IC 0.10-0.57). La higiene oral se asoció al área de residencia y nivel socioeconómico (NSE); los jóvenes urbanos tienen 5.6 veces más riesgo de tener una higiene óptima (95% IC 2.68-11.95) que los rurales y los jóvenes de NSE medio y bajo están protegidos de tener una higiene óptima (OR= 0.17 95% IC 0.04-0.66). La autopercepción de salud oral no se asoció a las variables estudiadas. Conclusiones: Los niños de establecimientos rurales presentaron los peores indicadores de salud oral. Los resultados evidencian inequidades de salud de los adolescentes de 12 años de los establecimientos educacionales municipalizados estudiados que ameritan el diseño de estrategias promocionales y preventivas acorde a sus necesidades.<br>Aim: To determine caries prevalence and risk factor associated to caries experience and oral health self perception in 12 year-old school children. The study makes comparisons between urban and rural children of Maule Region, Chile. Subjets and Methods: Cross sectional study in a convenience sample of 285 school children from four counties. Oral examinations were carried out by one calibrated clinician. Demographic variables, DMFT index, oral hygiene index, oral health self perception were measured, as well as the last visit to the dentist. Results: Caries prevalence was 63.9%. No statistical difference was found based on gender and residence area. Boys had 3.17 (95% IC 1.62-6.20) times more risk to have a DMFT = 0 than girls. Oral hygiene was also associated to DMFT=0 (OR=0.24 95% IC 0.10-0.57). Oral hygiene was associated to residence area and socioeconomic status. Urban boys were 5.6 times more at risk to have an optimal hygiene than rural boys (95% IC 2.68-11.95). Children from low and medium socioeconomic status were prevented to have an optimal hygiene (OR= 0.17 95% IC 0.04-0.66). Oral health self perception was not associated to any studied variable. Conclusion: Rural school children had the worst oral health indicators. These results show oral health inequities in 12 year-old school children. Thus, it is necessary to design health promotion and diseases prevention strategies according to their needs