Urinary mutagenicity as a biomarker in workers exposed to benzidine: correlation with urinary metabolites and urothelial DNA adducts

Urinary mutagenicity has been used in occupational and epidemiological studies for over two decades as a cost-effective, general biomarker of exposure to genotoxic agents. However, few studies have compared urinary mutagenicity to additional biomarkers determined among low- and high-exposed groups. To address this issue, we evaluated the relationship between urinary mutagenicity and other types of biomarkers in a cross-sectional study involving 15 workers exposed to the urinary bladder carcinogen benzidine (BZ, high exposure), 15 workers exposed to BZ-dyes (low exposure), and 13 unexposed controls in Ahmedabad, India. Urinary organics were extracted by C18/methanol and evaluated for mutagenicity in the presence of S9 in the Salmonella strain YG1024, which is a frameshift strain that overproduces acetyltransferase. The results were compared to biomarker data reported recently from the same urine samples (Rothman et al., Proc. Natl Acad. Sci. USA, 93, 5084-5089, 1996) that included a metabolite biomarker (the sum of the urinary levels of BZ + N-acetylbenzidine + N,N'-diacetylbenzidine) and a DNA adduct biomarker [a presumptive N-(3'-phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine (C8dG-ABZ) DNA adduct in exfoliated urothelial cells]. The mean +/- SE urinary mutagenicity (revertants/micromol of creatinine) of the low-exposure (BZ-dye) workers was 8.2 +/- 2.4, which was significantly different from the mean of the controls (2.8 +/- 0.7, P = 0.04) as was that of the mean of the high-exposure (BZ) workers (123.2 +/- 26.1, P < 0.0001). Urinary mutagenicity showed strong, positive correlations with urinary metabolites (r = 0.88, P < 0.0001) and the level of the presumptive C8dG-ABZ urothelial DNA adduct (r = 0.59, P = 0.0006). A strong association was found between tobacco use (bidi smoking) and urinary mutagenicity among the controls (r = 0.68, P = 0.01) but not among the exposed workers (r = 0.18, P = 0.11). This study confirms the ability of a biomarker such as urinary mutagenicity to detect low-dose exposures, identify additional genotoxic exposures among the controls, and correlate strongly with urinary metabolites and DNA adducts in the target tissue (urinary bladder epithelia) in humans.     

Religiosity as a protective or prognostic factor of depression in later life; results from a community survey in The Netherlands

OBJECTIVES: This study explored the possibility of using urinary 1-naphthol excretion as a marker of complex exposure among workers handling creosote. METHODS: Urine specimens of 6 workers from a creosote impregnation plant, where railroad ties were impreganted with coal tar creosote, were collected during 1 workweek, and the concentration of 1-naphthol was determined. 1-Naphthol in spot urine samples of 5 occupationally nonexposed male smokers was used as the background reference. Concurrently, naphthalene and 10 different polycyclic aromatic hydrocarbons (PAH) were determined in personal air samples. RESULTS: The mean airborne exposure of the workers was 1.5 mg/m3 for vaporous naphthalene, 5.9 micrograms/m3 for particulate PAH and 1.4 micrograms/m3 for PAH with 4-6 aromatic rings. The mean urinary concentration of 1-naphthol at the end of the workshift was 20.5 (range 3.5-62.1) mumol/l, whereas the referents' urinary concentration was below the detection limit (0.07 mumol/l). Airborne naphthalene correlated fairly well with 1-naphthol when measured at the end of the shift (r = 0.745). CONCLUSIONS: This method of analysis for 1-naphthol is sufficiently sensitive for measuring low occupational exposures to naphthalene. Low background exposures are, however, unlikely to result in detectable urinary levels of 1-naphthol. Since naphthalene is the most abundant compound in creosote vapor, urinary 1-naphthol determination serves well as a biological marker of exposure to vaporous creosote. Urinary 1-naphthol alone is not, however, a suitable marker for inhalatory or cutaneous exposure to PAH originating from creosote.     

Distribution and ultrastructure of the stomata connecting the pleural cavity with lymphatics in the rat costal pleura

Ethylene glycol levels were measured in 154 breathing zone air samples and in 117 urine samples of 33 aviation workers exposed to de-icing fluid (basket operators, de-icing truck drivers, leads and coordinators) studied during 42 worker-days over a winter period of 2 months at a Montreal airport. Ethylene glycol as vapour did not exceed 22 mg/m3 (mean duration of samples 50 min). Mist was quantified at higher levels in 3 samples concerning 1 coordinator and 2 basket operators (76-190 mg/m3, 45-118 min). In 16 cases workers' post-shift or next-morning urine contained quantities of ethylene glycol exceeding 5 mmol/mol creatinine (up to 129 mmol/mol creatinine), with most of these instances occurring in basket operators and coordinators, some of whom did not wear paper masks and/or were accidentally sprayed with de-icing fluid. Diethylene glycol was also found in a few air and urinary samples at levels around one tenth those of ethylene glycol. Urinary concentrations of albumin, beta-N-acetyl-glucosaminidase, beta-2-microglobulin and retinol-binding protein were measured and compared over various periods, according to subgroups based on exposure level and according to the frequency of extreme values. These analyses did not demonstrate acute or chronic kidney damage that could be attributed to working in the presence of ethylene glycol. In conclusion, this study does not suggest important health effects of exposure to de-icing fluid in this group of workers. Potential for overexposure exists, however, in certain work situations, and recommendations on preventive measures are given. In addition, these results suggest that other routes of absorption than inhalation, such as the percutaneous route, may be important and that urinary ethylene glycol may be a useful indicator of exposure to ethylene glycol.     

Septicemia due to Shigella. A case report and review of the literature

To develop a proper protocol for biological exposure monitoring of acetone, we evaluated whether exposure to acetone on the previous day affects the biological monitoring value at the end of a work day. One hundred and ten male workers exposed to acetone in three acetate fiber manufacturing plants were monitored using a liquid passive sampler on two consecutive working days after 2 days without exposure. Urine samples were collected at the start of the workshift and the end of the shift on both days for each subject. For ten exposed workers urine samples were collected approximately every 2 h during and after the first working day until the following morning. Acetone concentrations in urine (Cu) at the start of the first working day were 1.3 +/- 2.4 (range: ND-14.1) mg/l in nonexposed workers and 2.4 +/- 5.6 (range: ND-40.3) mg/l in exposed workers. The urinary acetone concentration at the beginning of the second working day indicated that urinary levels of acetone do not decline to background level by the following morning when exposure concentration exceeds 300 ppm. However, linear regression analysis demonstrated that the relationship between environmental exposure level and urine level was similar on the 1st day and the 2nd day. Thus, although urine acetone levels did not return completely to baseline after high exposures, under the present exposure levels the exposure on the previous day did not significantly affect urinary acetone at the end of the workshift of the next day.     

Evaluation of the FREEDOM O2, DC Concentrator, a portable oxygen concentrator capable of operating under car battery power

Many sensitive biomarkers are available for the surveillance of the early health effects of chemicals on humans. This study was conducted to evaluate the usefulness of glycosaminoglycans (GAG) as biomarkers of early kidney effects in exposure to 2-alkoxyethanols and their acetates. GAG were compared with effects on the urinary beta-N-acetylglycosaminidase activity (NAG). According to the results of the present study, the excretion rate of GAG was higher among women than men. On the other hand, the excretion rate of GAG was lower among exposed subjects than among the controls, and the level was decreased at the tested levels of exposure. The NAG activity was higher in most of the exposed groups than in the controls. The data indicated that an appropriate urinary limit value for ethoxyacetic acid was 30 mmol/mol creatinine in postshift samples and that this value corresponded to an 8-hour exposure level of 2 cm3/m3 2-ethoxyethylacetate. Urinary butoxyacetic acid excretion of 60 mmol/mol creatinine corresponded to the inhalation exposure level of 5 cm3/m3 2-butoxyethanol and its acetate in postshift samples.     

Chronic and acute respiratory effects among grain mill workers

Exposure to flour dust may induce chronic respiratory manifestations as well as acute ventilatory effects. We compared the prevalence of respiratory symptoms, ventilatory impairment, and variations in pulmonary function over the workshift in a group of mill workers exposed to wheat flour and in referent workers. One hundred and forty-two men exposed to flour in a mill and 37 referent workers were included in this study. Each subject completed a standardized questionnaire. Pulmonary function tests were performed before and after the workshift. The assessment of environmental exposure to flour showed high concentrations during some jobs with a high percentage of inhalable particles and a low concentration of respirable particles. The exposed workers had a significantly higher prevalence of usual cough and usual phlegm than the referents. The prevalence of asthma, based on the questionnaire, was similar. Before the workshift, the exposed workers had significantly lower mean lung function values for peak flow rate and forced expiratory flow rate at 75% of the vital capacity than the referents. After the workshift, all the lung function values showed a slight decrease, significant for forced vital capacity and forced expiratory volume during 1 s in both groups. Among the exposed workers, the asthmatic subjects had a significantly higher decrease across the shift than the nonasthmatic workers. This result is probably linked to bronchial hyperreactivity. Among nonasthmatic subjects, the decrease was larger in nonexposed workers than in exposed workers. A higher prevalence of respiratory symptoms and lower pulmonary function values were observed among mill workers by comparison with referents. Moreover, the data suggest that asthmatic status and the time of spirometric measurements need to be taken into account in epidemiological studies on exposure to airborne allergens. In addition, the study does not exclude a healthy worker effect with selection of dust-resistant subjects or better identification of asthmatic subjects among the workers exposed to an allergenic substance than among the nonexposed workers.     

Blood mercury in workers exposed to the preparation of mercury cadmium telluride layers on cadmium telluride base

Study was conducted in a group of 32 persons engaged in liquid phase epitaxial growth of mercury cadmium telluride (MCT) layers for nearly 11 years. Airborne mercury concentrations in work environment have been exceeding the threshold limit value of 0.05 mg/m3 recommended by ACGIHD. Hg concentration in workplace during peak working hours remained between 0.04-0.08 mg/m3. Findings were compared with 32 unexposed referents. Mercury value was estimated 1.60 +/- 0.20 (mean +/- SD) in control, and in Phase I and II, 10.72 +/- 1.34 ng Hg/ml and 8.08 +/- 1.15 ng Hg/ml of blood respectively. Results indicate a fall in blood mercury level during the second phase of study. But the values did not return to normal even after a gap of 3 months. An individual who met with a mercury accident showed 226 ng Hg/ml of blood which decreased to 25 ng/ml after 3 months. It is inferred from the present study that Hg level has increased significantly in MCT workers during working period, and also in non-working period, the values were higher than controls.     

High pressure liquid chromatographic determination of sorbitol in bulk sorbitol

An HPLC procedure for determining sorbitol in bulk sorbitol is described. An Aminex HPX-87 column (Bio-Rad) is used with water as a mobile phase and with a refractive index detector to monitor column eluate. Sorbitol is separated from pentaerythritol, erythritol, ribitol, ethylene glycol, propylene glycol, arabitol, galactitol, mannitol, iditol, and other carbohydrates. The precision of the sorbitol determination, characterized by a 95% confidence interval, corresponds to +/- 1.22%.     

Biological effect monitoring in industrial workers from the Czech Republic exposed to low levels of butadiene

Blood samples were collected twice (in 1993 and 1994) from 19 workers exposed to 1,3-butadiene and 19 matched controls. Three exposed and three control subjects were the same in 1993 and 1994. Personal passive dosimetry was performed in 1993 and twice in 1994 on the day preceding blood sampling. Mean exposure level in 1994 was 1.76 +/- 4.20 ppm (S.D.) and individual exposure levels ranged between 0.012 ppm (detection limit) and 19.77 ppm. Using the clonal assay, geometric mean of hprt mutant frequencies adjusted for cloning efficiency, age and smoking were, respectively, 7.85 (+/- 7.09) x 10(-6) and 10.14 (+/- 9.16) x 10(-6) in pooled (1993 plus 1994) exposed and control subjects. The difference was not statistically significant indicating that 1,3-butadiene did not induce a detectable increase in mutations at the hprt locus. A similar result was obtained for the 1994 subjects alone. There was no difference between adjusted geometric mean mutant frequencies of exposed and unexposed non-smokers or between exposed and unexposed smokers. Analysis of chromosomal aberrations in lymphocytes from 1994 subjects indicated that the percentage of aberrant cells was significantly enhanced in exposed subjects. In 1993 (data not shown), it was impossible to demonstrate a significant increase of aberrant cells in subjects exposed to 1,3-butadiene. Frequencies of micronuclei in cytochalasin-B blocked binucleate lymphocytes in exposed and unexposed 1994 subjects were not significantly different. This was also the case for earlier samples analyzed in the same plant. Using the comet assay for 1994 subjects, no statistically significant difference was found between the whole group of exposed and unexposed subjects. This was true for both the comet tail length and the percentage of DNA in the tail. In exposed smokers, however, the comet tail length was significantly longer than in unexposed smokers. Unexpectedly, in unexposed smokers the tail length was significantly shorter than in unexposed non-smokers. It was also unexpected that the percentage of DNA in the comet tail was significantly lower in exposed non-smokers than in unexposed non-smokers.     

Urinary kallikrein: a marker of blood pressure sensitivity to salt

We evaluated if a rat strain inbred for low urinary kallikrein excretion differs from normal-kallikrein Wistar rats regarding blood pressure levels in basal conditions and during alterations in sodium balance. Blood pressure was measured in unanesthetized rats on normal sodium intake. Then, blood pressure sensitivity to salt was evaluated over a period of 20 days of high sodium diet (0.84 mmol per g chow). Low-kallikrein rats showed greater systolic blood pressure levels (125 +/- 3 vs. 114 +/- 2 mm Hg in controls, P < 0.01) at nine weeks of age. Systolic blood pressure was increased after sodium loading in the low-kallikrein group and remained unchanged in controls (150 +/- 6 vs. 112 +/- 2 mm Hg, P < 0.01). This effect was associated with a reduced cumulative urinary excretion of sodium in the low-kallikrein rats. No group difference was found in the clearance of endogenous creatinine in basal conditions. Urinary creatinine excretion decreased during sodium loading, particularly in the low-kallikrein group. The group-difference in urinary kallikrein excretion found in basal conditions (6.85 +/- 0.31 vs. 20.74 +/- 1.71 nkat/24 hr in controls, P < 0.01) was enhanced by high salt diet (2.96 +/- 0.67 vs. 22.07 +/- 2.47 nkat/24 hr in controls, P < 0.01). In addition, renal kallikrein activity and content were reduced in low-kallikrein rats. The latter group showed a greater ratio of heart weight to body wt both in basal conditions and after sodium loading. The ratio of kidney weight to body wt was reduced after sodium loading. These results indicate that a genetically-determined defect in urinary kallikrein excretion is associated with a greater blood pressure sensitivity to salt, possibly due to altered renal sodium handling.     

Respiratory health and immunological profile of poultry workers

OBJECTIVES: To examine work-related respiratory symptoms in poultry workers, and to test for immunologically mediated responses to poultry-related agents. DESIGN: A cross-sectional survey of differentially exposed poultry workers and unexposed blue-collar workers. SETTING: Three poultry farms and a poultry plant in Gauteng (exposed workers) and a municipal workers' clinic in Johannesburg (controls). PARTICIPANTS: 134 poultry workers (85.4% of all eligible workers) and 122 controls (> 95% response rate). OUTCOME MEASURES: Respiratory symptoms plus allergy and hypersensitivity to poultry agents identified by skin-prick tests, and by the presence of specific IgE and IgG enzyme-linked immunoflow assay and nonspecific (radial immunodiffusion) antibodies. RESULTS: Smoking habits and atopic status were similar in the poultry workers and the controls. Symptoms were very common in poultry workers, for example work-related cough in 32% and work-related wheeze in 23% of highly exposed workers. Significantly more poultry workers than controls complained of chest symptoms (increasing with increasing exposure), and of eye, skin and nose irritation at work. More poultry workers than controls had symptoms consistent with asthma (e.g. 3%, 4%, 13% and 11% in controls and subjects with low, medium and high exposure, respectively), and symptom complexes associated with organic dust exposure. Five poultry workers had positive skin-prick test reactions to poultry-specific antigens, but none of the unexposed controls reacted. More poultry workers than controls had positive immunodiffusion test reactions to chicken feed, feathers and serum, and IgE to chicken faeces. There was no association between immunological status and respiratory symptoms. CONCLUSION: We found a very high prevalence of exposure-related symptoms in poultry workers; improved hazard control is strongly indicated. Tests of allergy and hypersensitivity were associated with exposure, but not with disease. The possibility of useful tests of sensitisation has not been excluded; a prospective study design is likely to be more rewarding than cross-sectional approaches such as in this study.     

Preparation and characterization of poly(propylene fumarate-co-ethylene glycol) hydrogels

We describe the preparation and bulk characterization of a cross-linked poly(propylene fumarate-co-ethylene glycol), p(PF-co-EG), hydrogel. Eight block copolymer formulations were made varying four different design parameters including: poly(ethylene glycol) (PEG) molecular weight, poly(propylene fumarate) (PPF) molecular weight, copolymer molecular weight, and ratio of PEG to PPF. Two different cross-linking formulations were also tested, one with a cross-linking monomer and one without. The extent of the cross-linking reaction and the degree of swelling in aqueous solution were determined on copolymer formulations made without a cross-linking monomer. The values of molecular weight between cross-links, Mc ranged from 300 +/- 120 to 1190 +/- 320 as determined from swelling data (n = 3). The equilibrium volume swelling ratios, Q, varied from 1.5 +/- 0.1 to 3.0 +/- 0.1. This ratio was found to increase with increasing PEG content in the copolymer and decrease with increasing PPF molecular weight. The values for complex dynamic elastic moduli magnitudes of E*, ranged from 0.9 +/- 0.2 to 13.1 +/- 1.1 MPa for the formulations with the cross-linking monomer, N-vinyl pyrrolidinone (VP) (n = 3). The ultimate tensile stresses on the formulations made with VP ranged from 0.15 +/- 0.03 to 1.44 +/- 1.06 MPa, and tensile moduli ranged from 1.11 +/- 0.20 to 20.66 +/- 2.42 MPa (n = 5). All of the mechanical properties increased with increasing PPF molecular weight and decreased with increasing PEG content in the copolymer. These data show that the physical properties of p(PF-co-EG) hydrogels can be tailored for specific applications by altering the material composition.     

Is zinc a limiting nutrient in the diets of rural pregnant Malawian women?

A subacute toxicity study with administration of tetraethylene glycol in dosages of 0-220-660-2000 mg/kg body weight to male and female Wistar rats via gavage was conducted in order to characterize a possible toxic action of this compound. The structurally related compound ethylene glycol is known to cause kidney toxicity. Therefore, special attention was paid to investigating possible toxic effects of tetraethylene glycol on this organ. In order to compare possible treatment-related effects of tetraethylene glycol with those known from ethylene glycol, a group of male and female rats was treated with 2000 mg ethylene glycol/kg body weight. Daily oral application of tetraethylene glycol over 4 weeks was tolerated without toxic effects up to and including 2000 mg/kg body weight. Daily oral application of ethylene glycol over 4 weeks resulted in treatment-related effects on the kidneys. A slight decrease in the urinary excretion of potassium, calcium and phosphate (males), a diminished pH-value of the urine, and a slight increase in osmolality (females) were observed. In both sexes excretion of oxalate was significantly increased and microscopic examination of urinary sediment revealed calcium oxalate crystals. Kidney weights of males and females were slightly elevated. Histopathology revealed crystals in renal tubuli, renal pelvis, and urinary bladder; tubulopathy and epithelial hyperplasia within the renal pelvis were also observed. Therefore, the study confirmed the kidney as target for ethylene glycol toxicity and gave no indications of tetraethylene glycol-induced toxic effects.     

Ambient, biological, and biological effect monitoring of exposure to polycyclic aromatic hydrocarbons (PAHs)

A novel strategy was utilised to assess the risk to health from exposure to polycyclic aromatic hydrocarbons (PAHs). Ambient monitoring was carried out by personal sampling. Urinary thioethers (UTh) and urinary 1-hydroxypyrene (1-HP) were utilised for biological monitoring. Urinary d-glucaric acid (UDGA) and sister chromatid exchange (SCE) in peripheral blood lymphocytes were used as biological effect markers. The population was categorised into exposed and control groups according to the external dose of PAHs. The excretion of 1-HP in the controls over the 3-day period showed a relatively stable baseline, while the exposed showed a significant increase over the same period of time. SCE frequency in the exposed population was significantly different from controls.     

Levels of cadmium, lead and zinc protoporphyrin absorption in different risk groups

We studied groups of workers, of pregnant women and of neonates exposed and unexposed to cadmium and lead at their place of work or in the environment. A total of 118 exposed and 28 unexposed workers were studied, together with 90 exposed and 100 unexposed pregnant women and neonates. Concentrations of cadmium and lead in the blood were determined by atomic absorption spectrophotometry. There were significant differences in cadmium concentrations between workers and neonates, and significant differences in lead concentrations between workers and pregnant women. We believe these differences are due mainly to high levels of pollution in the area studied.     

Reproductive hormone profile among pesticide factory workers

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.     

Changes in autonomic function as determined by ECG R-R interval variability in sandal, shoe and leather workers exposed to n-hexane, xylene and toluene

To clarify if autonomic nervous system effects might be associated with exposure to organic solvents, 30 sandal, shoe and leather workers exposed to n-hexane, xylene, and toluene, and 25 unexposed controls were examined using the coefficient of variation in electrocardiographic R-R intervals (CVRR), combined with the distribution of nerve conduction velocities (DCV). The C-CVRSA and C-CVMWSA (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) were also computed from component spectral powers using autoregressive spectral and component analyses. Concentrations of the metabolites of the solvents in urine samples taken in the morning before work were 0-3.18 (mean 1.39) mg/l for 2,5-hexanedione, 0.10-0.43 (mean 0.19) g/g creatinine (Cn) for methylhippuric acid, and 0.05-2.53 (mean 0.41) g/g Cn for hippuric acid. In the solvent workers, the CVRR and C-CVRSA were reduced significantly when compared with the unexposed controls. The faster velocities of the DCV as well as the sensory median nerve conduction velocity (SCV) were significantly slowed in the solvent-exposed workers. The SCV was significantly correlated with the CVRR and C-CVMWSA among the solvent workers. These data suggest that chronic exposure to some organic solvents may affect cardiac autonomic function (mainly, parasympathetic activity) in addition to faster myelinated fibers of the peripheral nerves. However, the absence of significant dose-effect relations among the solvent workers makes it difficult to definitively attribute the differences to specific solvent exposures.     

Effect of sex hormones on oxalate-synthesizing enzymes in male and female rat livers

PURPOSE: We studied the effect of changes in sex hormones on oxalate metabolism in rats. MATERIALS AND METHODS: Adult male and female rats were administered a precursor of oxalate, and the relationship between dose and urinary oxalate was examined. Levels of sex hormones were varied in rats and glycolate oxidase (GO) and serine pyruvate aminotransferase (SPT) activities were measured under the conditions of being fed tap water or loading with 0.5% ethylene glycol. In addition, urinary oxalate excretion was evaluated. RESULTS: Ethylene glycol and glycolate increased urinary oxalate concentration in male rats dose-dependently but less in female rats. There was almost no change during glycine loading in either male or female rats. GO activity was significantly lower in intact female and gonadectomized male rats. SPT activity was slightly higher in the female than in the male controls. There were no differences in urinary oxalate excretions between male and female rats. During ethylene glycol loading, GO and SPT activities were similar to those with tap water intake. However, urinary oxalate excretion increased to two times the control value in male rats but only slightly increased in female rats. CONCLUSIONS: Sex-related differences exist in the metabolic conversion of glycolate to oxalate in rats, and GO activity is promoted by testosterone. Although difference in GO activity has no physiological effect on oxalate synthesis, GO activity affects urinary oxalate excretion during ethylene glycol loading. We could also conclude that estrogen decreases GO activity in male rats from our results.     

Thyroid hormones and cytogenetic outcomes in backpack sprayers using ethylenebis(dithiocarbamate) (EBDC) fungicides in Mexico

Ethylenebis(dithiocarbamate) (EBDC) fungicides are used heavily in the United States. EBDCs (e.g., mancozeb, maneb) are metabolized to ethylene thiourea (ETU). The EPA classifies ETU as a carcinogen, based on thyroid and other cancers in rodents, and has restricted the use of EBDCs, while requiring workers to use protective equipment. There are no data on the potential carcinogenicity of EBDCs in humans, and there is only one study on human genotoxicity. ETU is known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. We have studied cytogenetic outcomes and serum thyroid hormone levels among 49 heavily exposed workers without protective equipment spraying EBDC on tomatoes in Mexico. We also studied 14 lightly exposed landowners and 31 nonexposed controls. Urinary ETU was used to compare exposure between groups. We found an increase in TSH (p = 0.05) among applicators compared to controls, but no decrease in thyroid hormone (T4). We found increases in sister chromatid exchange (p = 0.03) and in chromosome translocations (chromosome aberrations that persist through cell division) for applicators compared to controls (p = 0.05). However, the subset of reciprocal translocations showed a lesser increase (p = 0.24). Our data suggest that EBDCs affect the thyroid gland and the lymphocyte genome among heavily exposed workers. However, our data are limited to subclinical outcomes, are of borderline statistical significance, and should be interpreted with caution.     

Brain stem evoked potentials and visual evoked potentials in relation to the length of occupational exposure to low levels of toluene

In 49 printing-press workers occupationally exposed to toluene for approximately 21.6 years, the values of BEAP and VEP parameters were examined in relation to the length of exposure. With the exception of P2 wave, there was a significant increase in the latencies of all the BEAP waves examined as well as in the interpeak latency (IPL) P3-P4, whereas IPL P4-P5 decreased significantly with the length of exposure. The amplitude of all the VEP examined decreased significantly with the length of exposure. Toluene exposure was evaluated by measuring the concentration of toluene in peripheral blood and of hippuric acid in urine on Wednesday morning prior to the workshift, and of hippuric acid in urine after the workshift on the same day. According to the average concentration of hippuric acid in urine after the workshift, the levels of toluene exposure were estimated to range from 40-60 ppm. Evoked potentials were determined on Mondays 10-12 hours after a nonworking weekend.