Brain dopamine as a target for solvent toxicity: effects of some monocyclic aromatic hydrocarbons.

Adult male rabbits were exposed to toluene, xylene, styrene, ethylbenzene, vinyltoluene or were dosed with hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tubero-infundibular dopamine. Such an effect was also caused by treatment with mandelic and phenylglyoxylic acids. These results indicate that dopamine is a target for some solvents of their metabolites, the presence of a lateral vinyl- or ethyl-chain which may be biotransformed into alpha-keto acids being crucial for the effect. Experiments in vitro suggest that dopamine condenses non-enzymatically with reactive carbonylic groups of such and other alpha-keto acids, thus becoming ineffective as neurotransmitter. This mechanism might account for the neurobehavioral and neuroendocrine changes which have been reported in workers occupationally exposed to styrene and to some solvent mixtures.

Adrenal response in the pathogenesis of arterial hypertension in workers exposed to high noise levels.

Some neuroendocrine parameters known as stress indices were examined in two groups of healthy male workers in a glass factory: the first group (60 subjects) was exposed to high environmental noise levels [greater than 90 dB(A)]; the second group (52 subjects) was exposed to low noise levels [less than 78 dB(A)]. Subjects with histories of cardiovascular diseases or high arterial pressure were excluded from the study. In both groups serum catecholamines and cortisol, and urinary vanilmandelic and homovanillic acids were evaluated at the beginning and middle of morning and afternoon work-shifts, by high performance liquid chromatography with electrochemical detection. Norepinephrine, epinephrine and vanilmandelic acid were significantly increased (P less than 0.01) during work-shifts in the group exposed to 90 dB(A), compared with baseline levels and also with catecholamine levels in the group exposed to 78 dB(A). Serum dopamine, cortisol and homovanillic acid showed no significant differences. The increased stimulation of the sympatho-adrenal system in response to high and prolonged noise exposure might lead to an abnormal response of the cardiovascular system with increasing arterial pressure values.

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits.

Adult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3-methylstyrene), and 7-methyl-styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl- or ethyl-chain being crucial for the structure/activity relationship of such compounds.

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).

Regional alterations of brain catecholamines by styrene exposure in rabbits.

The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine. Styrene exposure produced a marked and dose-dependent decrease in striatal and tuberoinfundibular dopamine, associated with a consistent increase in homovanillic acid content in the same regions. Norepinephrine levels were unaffected by styrene exposure. The observed increase in catabolism of dopamine cannot be explained by the turnover time, which was not significantly different in the exposed as compared to the control rabbits. Competition of a styrene metabolite with dopamine for the vesicular storage capacity or a selective destruction of dopaminergic terminals are suggested as the possible mechanisms for styrene neurotoxicity.

Neuroendocrine effects of styrene on occupationally exposed workers.

The serum levels of prolactin (PRL), human growth hormone (HGH), thyroid-stimulating hormone (TSH), and the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in 30 females exposed to about 130 (range 65-300) ppm of styrene in the air and in 30 age-matched referents to show whether styrene exposure influences the dopaminergic tuberoinfundibular system (TIDA). The exposed subjects' serum levels of PRL were more than double the reference values and were significantly related to the urinary excretion of styrene metabolites, ie, to the sum of mandelic acid (MA) and phenylglyoxylic acid (PGA) in the "next-morning" urine spot sample. Such a relationship still proved to be statistically significant after the removal of the effects of age and duration of exposure with the method of partial correlation. The serum concentrations of HGH in the exposed workers were also higher than in the reference group. Though within the reference levels, the TSH values of the exposed subjects were significantly related to the urinary excretion of MA and PGA. These results are consistent with the dose-dependent depletion in tuberoinfundibular dopamine after experimental styrene exposure of rabbits.

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.

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.

[Chronic non-specific disease of the respiratory system and measurable alterations in workers in the chromium-plating industry (author's transl)]. / Esposizione a cromo ed alterazioni funzionali respiratorie in lavoratori dell'industria galvanica.

Lung function test performed on 26 chromium plating workers showed a high prevalence of obstructive disease and of change in DLCO. The connection between lung function impairment and occupational exposure to chromium is suggested by the relationship between respiratory changes and biological indices of chromium absorption. The prevalence and the severity of ventilatory impairment also show an increasing trend with the duration of the exposure, while the smoking habitus seems not to be important.

[Spirometric alterations in chromium-exposed welders (author's transl)]. / Alterazioni funzionali respiratorie in saldatori professionalmente esposti a cromo.

Lung function tests were examined on 28 welders using high chromium alloyed electrode for two years. Respiratory function change seem to be related to the duration of employment as welders. On the contrary, obstructive disease and alveolo-capillary impairment were found with same prevalence in groups of workers differently exposed to chromium. It presumably occurs because the exposure to chromium is quite short.