Alteraciones neuropsicológicas en trabajadores expuestos a neurotóxicos / Neuropsychological disorders in workers exposed to neurotoxics

La neurotoxicidad es un grave problema de salud pública debido al incremento de sustancias neurotóxicas y a la gran cantidad de trabajadores expuestos. Gran cantidad de sustancias de uso común en la industria. Tales como solventes, metales y plaguicidas, provocan alteraciones neurotóxicas a concentraciones por debajo de los límites permisibles, produciendo cambios importantes en la función psicológica y el comportamiento, que se expresan en trastornos funcionales que interfieren en las tareas cotídianas e incrementan la accidentabilidad. En este artículo se revisa la literatura científica sobre los efectos neurotóxicos de solventes, plomo, mercurio y plaguicidas, y se comentan aspectos metodológicos de interés para el diseño de investigaciones epidemiológicas. Como conclusión, es notoria la existencia de evidencias que demuestran el efecto neurotóxico de gran cantidad de sustancias usadas en la industria. Así mismo, consideramos importante continuar realizando investigaciones sobre el tema, y sobre todo, La necesidad de tomar medidas preventivas para proteger la salud del trabajador

Mechanisms of carcinogenicity of methyl halides.

Methyl chloride, bromide, and iodide are used as methylating agents. These compounds are mutagenic in short-term tests and do not require activation by exogenous S9 mix. In DNA-binding studies performed in rats and mice, 14C-labeled methyl chloride was given by inhalation, and methylation of DNA bases was examined. The compound did not lead to specific DNA adducts. In particular, methylation of DNA bases was not observed. In contrast, methyl bromide and methyl iodide, upon oral and inhalation administration to rats and mice, caused systemic DNA methylation. Specifically, 3-methyl-adenine, 7-methyl-guanine, and O6-methyl-guanine were formed. Long-term inhalation bioassays have been performed in rats and mice with methyl chloride and methyl bromide. Methyl chloride induced renal tumors, but only in male mice at the highest concentration tested (1000 ppm). Under these special conditions, a number of secondary effects occur subsequent to glutathione depletion in the target tissue, resulting in DNA damage (DNA-protein cross-links and probably DNA single-strand breaks). The particular coincidence of secondary high-dose effects precludes a risk extrapolation to man. Methyl bromide did not induce tumors in rats and mice when administered by inhalation. However, experimental data point to a possible local carcinogenic effect on the rat forestomach when the compound is given by gavage. A factor that accounts for the discrepancy between systemic DNA methylation and apparent noncarcinogenicity upon inhalation might be the preference of 7-N over O6 methylation of guanine. An extrapolation of the negative rodent inhalation bioassay of methyl bromide to man might be problematic because rodents metabolize methyl bromide very quickly whereas in humans there is a particular subpopulation that only poorly metabolizes the compound ("nonconjugators"). Such individuals can be characterized by incubation of erythrocytes with methyl chloride or methyl bromide and measurement of the substrate decline. Methyl iodide has been tested, with positive outcome, in early carcinogenicity bioassays not based on modern methodology. However, these results, along with the proven systemic methylating potency of methyl iodide, argue in favor of a carcinogenic effect of the compound.

Neurophysiological and psychological disorders and occupational exposure to organic solvents.

A number of reports, particularly from Scandinavian countries, claim that painters and workers in other trades in which prolonged occupational exposure to organic solvents may occur develop a type of mental illness characterized principally by impairment of memory and co-ordination and some deterioration of personality. The condition, called 'organic solvent disease', is recognized as a cause of premature retirement and is classed as an occupational disease in certain countries. The conclusions of these reports have been contested and the existence of such a disease entity has been questioned. The publications reporting adverse neurological, neurophysiological and psychological disorders in solvent-exposed workers, and the methods used to determine adverse effects, have therefore been evaluated. In addition, data from animal behavioural studies have been examined but were found to have little or no to have little or no relevance to the reported human disease. The human data indicate that, of the solvents studied, only CS2 provided clear evidence of neurotoxic damage detectable by clinical and pathological examination as well as by neurophysiological measurements (e.g. nerve conduction velocity and nerve action potentials) or neuropsychological techniques (e.g. Rorschach inkblot test and WAIS intelligence tests). In the case of several other solvents and mixtures of solvents commonly used in industry, the evidence of CNS impairment, based principally on the response to questionnaires and the results of neuropsychological and neurophysiological examinations was questionable. A critical evaluation of the reliability of these methods in detecting minor deviations from normal and of their ability to provide acceptable evidence of CNS dysfunction or damage leaves little doubt that these methods are of value in investigating personality, intelligence and memory in the clinical examination of individual patients. However, evidence indicates that they are not suitable for use in epidemiological studies, principally because the variability of response in normal individuals is ill-defined and insufficiently investigated. The same conclusion was arrived at in evaluating the contribution of electroencephalography, computerized axial tomography scanning and other electrophysiological examinations to the diagnosis of brain changes in groups of solvent-exposed and unexposed workers. Furthermore, the personality changes identified (by neuropsychological tests) in painters and other workers exposed to solvents could well be produced by ageing, exposure to lead or mercury, excessive alcohol intake, psychoactive drugs or the ordinary stresses of everyday life.(ABSTRACT TRUNCATED AT 400 WORDS)