Assessment of exposure to pesticides in rural workers in southern of Minas Gerais, Brazil.

The aim of the study was to assess of occupational exposure to pesticides in rural workers using genotoxicity test, bioindicators and clinical evaluation. Blood, urine and buccal samples from persons, rural workers exposed to a complex mixture of pesticides with organophosphates (n=94) and without organophosphates (n=94) were collected to compare the activities of cholinesterases, the levels of urinary dialkyl phosphates, genotoxicity data, from a cytome assay. Biomarkers were analysed by traditional/published methods Control group consisted of 50 other persons, non- occupationally exposed to pesticides from the city of Alfenas, Minas Gerais, Brazil. All subjects underwent a clinical evaluation. In the group exposed to organophosphates, the activity of acetylcholinesterase, butyrylcholinesterase and total cholinesterase was lower by 63.8%, 12.8%, and 14.8%, respectively, and 92.6% of the group had dialkyl phosphates present in their urine. The cytome assay was used to measure biomarkers of DNA damage (micronuclei and/or elimination of nuclear material by budding), cytokinetic defects (binucleated cells), and proliferative potential (basal cell) and/or cell death (condensed chromatin, karyorrhectic, pyknotic, and karyolytic cells). The group exposed to organophosphates showed significant changes in all these parameters compared to the control group and showed significant changes in budding, condensed chromatin and karyolytic cells compared with the group non-exposed to organophosphates. Data from the clinical evaluation showed significant changes in the central nervous, respiratory and auditory systems. The studied biomarkers are able to distinguish occupational and environmental exposure to pesticides and the data showed hazardous exposure to organophosphates and afforded valuable data to estimate the risk to cancer development.

Chemical signals of elephant musth: temporal aspects of microbially-mediated modifications.

Mature male African (Loxodonta africana) and Asian (Elephas maximus) elephants exhibit periodic episodes of musth, a state in which serum androgens are elevated, food intake typically decreases, aggressiveness often increases, and breeding success is enhanced. Urine is a common source of chemical signals in a variety of mammals. Elephants in musth dribble urine almost continuously for lengthy periods, suggesting that the chemicals in their urine may reveal their physiological condition to conspecifics. We investigated the volatile urinary chemicals in captive male elephants using automated solid phase dynamic extraction (SPDE) and gas chromatography-mass spectrometry (GC-MS). We found higher levels of alkan-2-ones, alkan-2-ols, and some aromatic compounds in urine from males in musth than in urine from non-musth males or from females. Levels of ketones and alcohols increased as the urine aged, likely due to microbial metabolism of fatty acids. Protein-derived aromatic metabolites also increased in abundance after urination, likely due to microbial hydrolysis of hydrophilic conjugates. We suggest that microbes may play an important role in timed release of urinary semiochemicals during elephant musth.

1-Iodo-2 methylundecane [1I2MU]: an estrogen-dependent urinary sex pheromone of female mice.

In our previous investigations, urine of female mice contained specific compounds, namely isocroctylhydrazine, 4-methyl-2-heptanone, and azulene during proestrus, whereas during estrus it contained 1-H-cyclopop.e.azulene, caryophyllene, and copanene. Furthermore, 1-iodo-2 methyl undecane (1I2MU), present during both proestrus and estrus, was regarded as a putative estrus-specific chemo-signal. The primary objective of the present study was to determine the estrogen-dependency of the above-mentioned compounds, including 1I2MU. Furthermore, the effect of these compounds on pre-mating behavior, e.g., sniffing, licking, and grooming, were recorded to determine their role as sex pheromones. Based on gas chromatography linked mass spectrometry (GC-MS) of urine samples, profiles in oophorectomized female mice had 14 major peaks. Furthermore, neither 1I2MU (nor other estrus-specific compounds) were detected in the urine of these mice, although they were detected in urine of proestrus and estrus mice. In addition, 1I2MU was not detected in urine of prepubertal mice. It was noteworthy that both 1I2MU and 4-methyl-2-heptanone reappeared in estrogen-treated females. Based on pre-mating behavioral analysis, 1I2MU was the compound most preferred by males. In conclusion, production of 1I2MU was estrogen-dependent in females, and it enhanced reproductive activities in males.

Chemical characterization of bovine urine with special reference to oestrus.

Cows' urine was analysed by gas chromatography mass spectrometry (GC-MS). The profiles from preovulatory, ovulatory and postovulatory samples were compared to establish any qualitative and quantitative differences that might have potential value in olfactory communication. Dichloromethane was used as the solvent for extraction of the compounds. Seven different compounds were detected, of which only two were common to all the chromatograms. The chemical profile of oestrous urine was distinguished by the presence of two specific compounds, viz. di-n-propyl phthalate and 1-iodoundecane, that were not found in the other samples. As oestrous urine has been shown to elicit sexual behaviour in cattle, these two characteristic peaks may represent important chemical compounds that elicit signals that allow the bull to detect 'oestrous odours'.

The metabolism of n-nonane in male Fischer 344 rats.

The urinary metabolites of n-nonane in male Fischer 344 rats, after administering the hydrocarbon by gavage, included gamma-valerolactone, delta-hexanolactone, 2,5-hexanedione, delta-heptanolactone, 1-heptanol, 2-nonanol, 3-nonanol, 4-nonanol, 4-nonanone and 5-methyl-2-(3-oxobutyl)furan. Metabolism strongly favored the formation of monoalcohols and lactones, which are the products of appropriately substituted hydroxy carboxylic acids. The metabolites were identified using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). High pressure liquid chromatography (HPLC) permitted the detection of the dicarboxylic acids malonic acid and glutaric acid in the n-nonane dosed rat urines.

Experimental neurotoxicity and urinary metabolites of the C5-C7 aliphatic hydrocarbons used as glue solvents in shoe manufacture.

Rats were intermittently exposed (9 to 10 h/d, 5 to 6 d/week) to controlled concentrations of single analytical grad solvents in ambient air. After periods ranging from 7 to 30 weeks the animals were perfused with glutaraldehyde and samples of nerves were processed for light microscopy of sections and of teased fibers. Animals treated with n-hexane at 5000 ppm (14 weeks) or 2500 ppm (30 weeks) developed the typical giant axonal degeneration already described in rats treated continuously with 400 to 600 ppm of the same solvent for 7 weeks or more. No such alterations were found in rats subjected to the following intermittent respiratory treatments: n-hexane 500 ppm (30 weeks) or 1500 ppm (14 weeks), cyclohexane 1500 or 2500 (30 weeks), n-pentane 3000 ppm (30 weeks), n-heptane 1500 ppm (30 weeks), 2-methylpentane 1500 ppm (14 weeks), and 3-methylpentane 1500 ppm (14 weeks). The following metabolites were found in the urine of rats according to treatment (in parenthesis): 2-methyl-2-pentanol (2-methylpentane); 3-methyl-2-pentanol and 3-methyl-3-pentanol (3-methylpentane), 2-hexanol, 3-hexanol, gamma-valerolactone, 2,5-dimethylfuran, and 2,5-hexanedione (n-hexane). 2-Hexanol was found to be the main urinary metabolite of n-hexane, while 2,5-hexanedione was present only in a lesser proportion. This feature of rat metabolism suggests that in this species 2,5-hexanedione reaches an effective level at its site of action during intermittent respiratory treatment with n-hexane with difficulty and explains the high concentrations necessary to cause polyneuropathy in rats subjected to this treatment.

Metabolism of a n-paraffin, heptadecane, in rats.

14C-heptadecane incorporated in rat diet was largely absorbed, and a balance study showed extensive 14CO2 excretion (65%). There was no elimination of the hydrocarbon in the urine, and only minute quantities of labeled metabolites. Radioactivity in the feces was entirely in heptadecane. About 7% of the heptadecane absorbed was stored in the carcass, whereas the rest was omega-oxidized to heptadecanoic acid. This fatty acid was incorporated into neutral lipids and phospholipids, underwent the normal fatty acid degradation pathway, and contributed to the synthesis of lipids, including fatty acids, squalene and cholesterol, and nonlipids (7-10%). Heptadecanoic acid was desaturated to heptadecenoic acid. The even distribution of radioactivity in the fatty acids of the various phospholipid classes indicated that heptadecane did not interfere with the biochemical mechanisms of these functional lipids.

Some metabolites of 1-bromobutane in the rabbit and the rat.

1. Rabbits and rats dosed with 1-bromobutane excrete in urine, in addition to butylmercapturic acid, (2-hydroxybutyl)mercapturic acid, (3-hydroxybutyl)mercapturic acid and 3-(butylthio)lactic acid. 2. Although both species excrete both the hydroxybutylmercapturic acids, only traces of the 2-isomer are excreted by the rabbit. The 3-isomer has been isolated from rabbit urine as the dicyclohexylammonium salt. 3. 3-(Butylthio)lactic acid is formed more readily in the rabbit; only traces are excreted by the rat. 4. Traces of the sulphoxide of butylmercapturic acid have been found in rat urine but not in rabbit urine. 5. In the rabbit about 14% and in the rat about 22% of the dose of 1-bromobutane is excreted in the form of the hydroxymercapturic acids. 6. Slices of rat liver incubated with S-butylcysteine or butylmercapturic acid form both (2-hydroxybutyl)mercapturic acid and (3-hydroxybutyl)mercapturic acid, but only the 3-hydroxy acid is formed by slices of rabbit liver. 7. S-Butylglutathione, S-butylcysteinylglycine and S-butylcysteine are excreted in bile by rats dosed with 1-bromobutane. 8. Rabbits and rats dosed with 1,2-epoxybutane excrete (2-hydroxybutyl)mercapturic acid to the extent of about 4% and 11% of the dose respectively. 9. The following have been synthesized: N-acetyl-S-(2-hydroxybutyl)-l-cysteine [(2-hydroxybutyl)mercapturic acid] and N-acetyl-S-(3-hydroxybutyl)-l-cysteine [(3-hydroxybutyl)mercapturic acid] isolated as dicyclohexylammonium salts, N-toluene-p-sulphonyl-S-(2-hydroxybutyl)-l-cysteine, S-butylglutathione and N-acetyl-S-butylcysteinyl-glycine ethyl ester.