Occupational genotoxicity assessment by mutagenicity assays.

Mutagenic activity measured by Ames test and by gene conversion, point mutation and mitochondrial mutability in Saccharomyces cerevisiae D7 strain was determined in the indoor environment of a glass factory. The results suggest that the increase in mutagenicity of air sample collected near the machinery is due to the thermal decomposition of oils. Modified assays were therefore compared for their ability to detect mutagens contained in urinary concentrates of exposed workers. The bacterial tests were performed by microsuspension assay in TA98, TA100 strains and in YG1024, YG1029 strains which overproduce O-acetyltransferase. Significant differences are evidenced both in the eukaryotic and prokaryotic systems.

A cross-sectional survey of kidney function in refinery employees.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

Urinary excretion of brush-border antigen revealed by monoclonal antibody: early indicator of toxic nephropathy.

Mouse monoclonal antibodies against brush-border antigens of the proximal tubule of human kidney were produced by the hybridisation technique. The urinary excretion of a brush-border protein with an apparent molecular weight of 50 000 (BB-50) was measured by a sandwich enzyme-linked immunosorbent assay with a mouse IgG1 against BB-50 and a polyclonal rabbit antiserum against human kidney as coating and second antibodies. The urinary excretion of BB-50 was fifty times higher in patients treated with cisplatin than in a matched control group and twice as high in workers occupationally exposed to water-soluble chromium(VI) compounds as in their matched controls. These findings suggest that the urinary excretion of kidney antigens revealed by monoclonal antibodies is a very sensitive and specific test for the assessment of toxic nephropathies.

Styrene metabolism and striatal dopamine depletion in rabbits.

The striatal concentration of dopamine (DA), norepinephrine (NE), and homovanillic acid (HVA) was assessed in adult male rabbits exposed to styrene vapours or dosed with mandelic acid (MA), phenylglyoxylic acid (PGA) and phenylglycine (PG). Styrene exposure produced a marked and dose-dependent decrease in striatal DA, concomitant with a consistent increase in HVA. The same effects were caused by i.p. administration of PGA and PG, but not of MA. The increased catabolism of DA was concomitant with a normal turnover time after inhibition of tyrosine hydroxylase by the administration of methyl-p-tyrosine. The amination of PGA to PG with a subsequent competition of the latter with DA for the vesicular storage capacity is suggested as the possible mechanism for styrene-induced brain dysfunction.

n-Hexane metabolism in occupationally exposed workers.

Lung uptake and excretion of n-hexane were studied in ten workers in a shoe factory. Simultaneous samples of inhaled and alveolar air were collected with the aid of a Rhan-Otis valve, personal samplers, and charcoal tubes. Alveolar excretion was monitored during a six hour postexposure period. Uptake was calculated from lung ventilation, the retention coefficient, and environmental concentrations. The amount of exhaled n-hexane was calculated from the decay curve. According to the experimental data, alveolar retention was about 25% of the inhaled n-hexane, corresponding to a lung uptake of about 17%. The postexposure alveolar excretion was about 10% of the total uptake. The main metabolites of n-hexane were identified and measured by capillary GC/MS in spot urine samples collected before, at the end, and 15 hours after the same working shift. Urinary concentrations were low, though related to n-hexane in the air. 2,5-Hexanedione in the end of shift samples gave the best estimate of overall exposure. About 3 mg/g creatinine of 2,5-hexanedione would correspond to about 50 ppm of n-hexane in the air (mean daily exposure).

Enzyme-linked immunosorbent assay of retinol-binding protein in serum and urine.

This highly sensitive method for determining retinol-binding protein in human serum and urine is based on a double-antibody "sandwich"-type enzyme-linked immunosorbent assay. The assayable concentration range is 0.8-48 micrograms/L, the detection limit 0.2 micrograms/L. Within-assay coefficients of variation for 10 determinations at two different concentrations were 5.5 and 5.8%. The corresponding between-assay CVs were 7.9 and 9.2%. We saw no interference from any components of urine or serum. The mean urinary excretion by 30 healthy subjects, as determined by this method, was 101 micrograms/g of creatinine (SD 38.8). The concentration in serum averaged 43 mg/L (SD 12.1).

Early indicators of renal damage in workers exposed to organic solvents.

In order to investigate the renal function, a cross-sectional study was carried out on four groups of workers significantly exposed to a mixture of alicyclic and aliphatic C5-C7 hydrocarbons, to styrene, to a mixture mostly composed of toluene and xylenes and to chlorinated hydrocarbons, respectively. The study involved 438 workers. Exposure was characterized by means of urinary metabolites, or by means of environmental measures, when biological indicators were not available. The renal function impairment indicators included total proteinuria, albuminuria and urinary excretion of muramidase (E.C. 3.2.1.17) and beta-glucuronidase (E.C. 3.2.1.31). The trend of these parameters provides some evidence of renal damage due to occupational exposure to organic solvents and suggests that the lesions are mild and tubular rather than glomerular.

Neurophysiological changes in workers exposed to organic solvents in a shoe factory.

Motor conduction velocity (MCV) was measured in the median, ulnar, and peroneal nerves of 52 referents and 95 workers from a shoe factory, in a search for dose-effect and dose-response relationships between exposure to organic solvents and subclinical impairment of the peripheral nervous system (PNS). According to the environmental concentrations, the exposure was expressed as the sum of the products between the median hygienic effect (ranging from 0.08 to 2.89) and worktime (from 1 to 29 a) in every job. The motor action potential (MAP) amplitudes, durations and shapes of the exposed workers were significantly affected even if to a different extent and significance level when compared to those of the MCVs of the referents. The MCVs of the median (t = 3.17, p less than 0.01) and peroneal (t = 2.11, p less than 0.05) nerves were reduced as compared to reference values. In the exposed group, the MCV of the median nerve was negatively correlated with exposure score (r = 0.45, p less than 0.01) but not with age. No relationship was found between MVCs of the ulnar and peroneal nerves and exposure. The MCV of the median nerve was particularly slow in a subgroup of workers with an exposure score of greater than 20 (t = 2.30, p less than 0.05 vs the other exposed workers; t = 5.56, p less than 0.01 vs the referents). This exposure score represents only 50% of the maximum allowable score for a worktime of 40 a. Even if none of the examined workers showed clinical signs of polyneuropathy, evidence of subclinical effects on the PNS were found among subjects with long-term exposure to hexacarbon mixtures. Therefore, our results suggest the need for a lowering of current threshold limit values at least for n-hexane.

n-Hexane-induced changes in nerve conduction velocities and somatosensory evoked potentials.

Fifteen women from a shoe factory were examined clinically and their cerebral evoked responses to 256 electrical stimulations of the median nerve were averaged. Neurophysiological investigations included maximal motor (MCV) and distal sensory (dSCV) nerve conduction velocity measurement on ulnar, median, and peroneal nerves. A referent group was composed of 15 age-matched women without exposure to neurotoxic chemicals. MCVs and dSCVs of the exposed workers were significantly reduced vs referents, while P15 and N20 components of the somatosensory evoked potentials (SEP) showed an increased latency. A negative linear relationship was found between dSCV and P15 latency. However, two subjects with an abnormally low dSCV showed normal SEP latency, and two other subjects displayed abnormal SEP latency, while their dSCV was in the normal range. Therefore, SEP investigation may give additional information on nervous system function, even in subjects with peripheral neuropathy. The later SEP components were much flatter in the exposed than in the referent group, suggesting some neurotoxic effects of n-hexane on the central nervous system too.

Absorption and alveolar excretion of cyclohexane in workers in a shoe factory.

The lung uptake and excretion of cyclohexane were studied in five workers and three volunteers in a shoe factory. Air samples were collected from the breathing zones with personal samplers, and simultaneous samples of inhaled and alveolar air were collected with the aid of a Rhan-Otis valve. Cyclohexane was absorbed on activated NIOSH approved charcoal tubes. The uptake was calculated from the pulmonary ventilation, the retention coefficient and environmental concentration. Alveolar excretion was monitored during a 6 h post-exposure period. The amount of exhaled cyclohexane was calculated from the decay curve. According to experimental data, the alveolar retention of cyclohexane is about 34% of the inhaled dose. This corresponds to a lung uptake of 23%. The post-exposure alveolar excretion does not exceed 10% of the total uptake. The difference between respiratory uptake and excretion indicates that the amount metabolized may be very large. Nevertheless, the urinary excretion of the main metabolites, cyclohexanol and cyclohexanone, was only about 1% of the absorbed dose.

Organic solvents and chronic glomerulonephritis: a cross-sectional study with negative findings for aliphatic and alicyclic C5-C7 hydrocarbons.

Proteinuria, albuminuria, urinary beta-glucuronidase and serum creatinine were estimated in 182 workers exposed to organic solvents in four shoe factories, as well as 30 workers with past exposure and 80 control subjects. Ambient air concentrations at each workplace were also measured. In most of these samples, the concentration of organic solvents exceeded the ACGIH recommended threshold limit value for the mixture. Total protein excretion was significantly elevated in exposed workers, although none of the workers had abnormal albuminuria or serum creatinine. Four had increased lysozymuria. There was also a simultaneous elevation of beta-glucuronidase. These findings suggest that a mild and presumably reversible tubular lesion, but not glomerular damage, may occur in workers occupationally exposed to C5-C7 hydrocarbon mixtures.