Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : Cobalto

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 11135 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del cobalto, aplicaciones industriales, efectos en los humanos, metabolismo, indicadores biológicos...

Biological Monitoring of Pesticide Exposure: a review. Introduction.

Pesticides are used worldwide in agriculture, industry, public health and for domestic applications: as a consequence, a great part of the population may be exposed to these compounds. In spite of this extensive use, knowledge on the health risks associated with prolonged exposure is rather poor, and major uncertainties still exist. Epidemiological observations in man have so far produced little conclusive information, mainly because of weaknesses in exposure assessment. Therefore, information on the type and levels of exposure is fundamental in order to better understand and characterize risk to human health. Exposure assessment can be carried out via measurement of environmental concentrations, as well as via determination of the chemical or its metabolites in body tissues (biological monitoring). Besides indices of internal dose, biological monitoring also includes measurements of early effects attributable to interaction between the chemical agent and the human body. Biological monitoring has the advantage, over environmental monitoring, of determining the dose actually absorbed via any possible route: differences in absorption can be taken into account. whether they are due to biological variability or to use of protective equipment. When, in some cases, a combination of occupational and non-occupational exposure occurs, this also can be taken into consideration by biological monitoring. Few reference documents have been published on biological monitoring of pesticides. For this reason, the Office of Occupational Health of the World Health Organization gave ICPS a mandate to prepare a monograph specifically addressed to reviewing methods for biological monitoring of pesticide exposure. This review is based on more than 300 studies published over the period 1980-1999. For the most representative chemical classes, the available biological exposure indices are reported. Both indices of internal dose and. when available, of early effects are discussed. The reported tests were used to monitor exposure of pesticide applicators in agriculture and public health, manufacturing and formulating workers. subjects poisoned after accidental exposure or attempted suicide, volunteers involved in pharmacokinetic studies, as well as sub-groups of the general population exposed to environmentally persistent pesticides. Single chapters deal with organophosphorus insecticides, carbamate pesticides, dithiocarbamates, phenoxyacids, quaternary ammonium compounds. coumarin rodenticides, synthetic pyrethroids, organochlorine pesticides, chlorotriazines, and pentachlorophenol.

Impact of pesticides to groundwater resources in an alluvial plain using a geographical information system.

A methodology to evaluate the impact of pesticides to drinking water resources in an agricultural region has been applied in an Italian alluvial plain using a Geographical Information System (GIS). With this technology it is possible to store, process and represent geographical data and update them according to the environmental characteristics. The studied area, covering a surface of 500 km2, is located immediately south of Milan, in the alluvial plain of the Po river. The DRASTIC model (1) has been utilized in order to evaluate the intrinsic vulnerability of aquifers, DRASTIC is a quantitative method proposed by EPA to identify pollution potential especially referred to pesticides in USA. The application of this model, combined with data of land use has provided maps identifying areas at risk for groundwater pollution. Information derived from risk maps is of primary importance in territorial planning such as: selection of areas to be monitored, identification of areas to be protected, correct management of agricultural practices and use of pesticides. These maps should provide an useful instrument for agricultural and territorial management.

[Paraquat-induced acute dermatitis in a child after playing with a discarded container]. / Dermatite acuta da paraquat in bambina che ha utilizzato per gioco un contenitore abbandonato.

The improper use of pesticide waste containers is a significant risk in rural areas, especially where appropriate systems of draining off refuse are lacking. A case is reported of an eight-year-old child who had played with the abandoned Paraquat container. After contamination with the pesticide she showed several II degree caustic lesions on both thighs and knees, associated with a mild erythemato-desquamative cheilitis and a "strawberry tongue". Common laboratory findings did not reveal any kidney, liver and/or red/white cell alterations and the chest X-ray was normal even several months after the accident. No physical consequences ensued, except for hyperchromic pigmentation on the legs. Where empty pesticide containers are not properly collected, they can represent a risk of pesticide exposure for the general population. They can also be a potential source of pollution for superficial water and soil. In the district where the accident was reported it was estimated that empty containers made up 7% of the weight of the 146,330 kg of pesticides sold to local farmers in 1993, of which about 10,400 kg was burned, buried and dispersed in the soil. Within the framework of a global pesticide prevention programme launched by the Regional Government of Lombardy, local health authorities, with the contribution of farmers, are carrying out a project for the proper collection of empty pesticide containers.

Programmes and activities of the International Centre for Pesticide Safety.

The International Centre for Pesticide Safety (ICPS) is a research unit of the National Health Service created by the Government of the Region of Lombardy at the proposal of the World Health Organization-Regional Office for Europe, in cooperation with the University of Milan, and in agreement with the Italian Ministry of Health. ICPS operates in the following areas of activity: information and documentation on pesticide toxicity to man and environment, epidemiological, toxicological and clinical research on effects of pesticides in man; training and education of personnel in public health, assessment of environmental and health impact of pesticides by means of Geographical Information Systems, laboratory research for development and standardisation of methods for residue measurement in environmental and biological media. ICPS is also a centre of international meetings and continuing education courses. A number of projects carried out or underway at ICPS are briefly described in this paper.

Biological monitoring of human exposure to atrazine.

Atrazine exposure was evaluated in six manufacturing workers by personal and biological monitoring. Total atrazine exposure varied from 10 to 700 mumol per workshift and total urinary atrazine excretion accounted for 1-2% of the external dose. The spectrum of the urinary atrazine metabolites comprises bi-dealkylated (80%), deisopropylated (10%), deethylated (8%) and unmodified atrazine (2%). The metabolites are eliminated in urine in slightly longer than 24 h: 50% of the amount is excreted in the first 8 h following the workshift.

Association between silica exposure and necrotizing crescentic glomerulonephritis with p-ANCA and anti-MPO antibodies: a hospital-based case-control study.

A hospital-based case-control study was carried out to investigate the association between ANCA positive rapidly progressive glomerulonephritis (RPGN) and occupational exposure to silica dust. All ANCA positive male patients admitted to the Department of Nephrology of the University of Brescia between 1987 and 1992 were enrolled in the study as cases. The controls were pts of the same age, admitted at the Department immediately before or after the cases, affected by other renal diseases. Seven of the 16 cases and one of the 32 controls, had a positive history for jobs exposing to silica dust (relative risk 14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO antibodies in 6/7 of exposed pts. The review of renal histology showed a distinctive glomerular lesion consisting in peripheral nodular areas of glomerular sclerosis, in addition to the crescentic necrotizing glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.

The microdose problem and the most commonly used metals.

On the basis of recent research a relationship may exist between microexposure to metals and certain diseases (e.g. neurological and cardiovascular diseases) which occur in the later stages of life. This fact must be kept firmly in mind in view of the implications for the quality of health, considering the increase in average life expectancy. Moreover, it will be necessary to re-identify the critical organ for each metal, bearing in mind that the effects are altered in low level exposure conditions.

[Evaluation of the effects of reduced glutathione in subjects with acquired and congenital changes in heme biosynthesis]. / Valutazione degli effetti del glutatione ridotto in soggetti con alterazioni acquisite e congenite della biosintesi dell'eme.

In order to evaluate the possible therapeutical effects of reduced glutathione in subjects affected by acquired or congenital heme biosynthesis alterations, two groups of subjects have been considered: the first, of 5 subjects with abnormal lead absorption, the second of 10 patients suffering from porphyria cutanea tarda (PCT). The drug was administered i.v. at the dosage of 600-1200 mg for a variable period of 3-5 days in the first group, for 7-10 days in the patients with PCT. In the lead-exposed subjects an increase in the activity of ALA-dehydratases enzyme was observed, with a decrease in the urinary excretion of delta-aminolevulinic acid, and a decrease in the percentage of urinary coproporphyrins as well. In the patients with PCT, after the therapy, a relevant reduction of urinary excretion of porphyrins, prevalently uro- and heptaporphyrins, was noticed. The results of this preliminary study suggest that glutathione can exert an effect of "normalization" on heme biosynthesis when altered in acquired and/or congenital conditions.

Significance and validity of a shortened lead chelation test.

We evaluated the chelation test in 38 subjects exposed to lead or with suspected lead exposure, comparing the values of lead excretion at the 3rd h (PbU EDTA/3-h) and at the 24th h (PbU EDTA/24-h) after EDTA administration. Good correlation exists between PbU EDTA/3-h and PbU EDTA/24-h (r = .86) and between them and the main biological indicators of dose and effect of lead. When a second chelation test was performed in 15 subjects, a slightly better r coefficient (.93) was observed between the two tests, without reaching statistical significance. It seems difficult, in terms of the type of exposure that we considered, to use the 3-h test, on an individual basis, to predict the PbU EDTA/24-h values.

[Pathology caused by microdoses of chemical substances]. / Patologia da microdosi di sostanze chimiche.

Improvement in environmental conditions in industry is producing a progressive reduction in the dose of absorbed substances. This has repercussions on the work of the occupational health physician, who now has to face a new set of problems, problems which at the same time offer occasions for further research in risk assessment of chemical agents. The most obvious finding, which has perhaps been handled more systematically, concerns the change in occupational diseases, whence the need to extend designs and protocols of health surveillance. The expected effects of occupational exposure to low doses of a chemical fall within the category of what may be defined as long-term effects, carcinogenic effects and, above all, effects involving systems or apparatuses that are sensitive to low doses but over long periods, such as, for example, the immune and the reproductive systems. This new situation than has repercussions on biological monitoring: in the first place on the problem of setting reference values and on the study and control of confounding factors; secondly, on the predictivity of the biological indicators used. In some cases, in fact, the indicators of dose that the occupational health physician has learnt to use and on which his approach to prevention his based, proved to be no longer predictive in such new exposure situations.

Behaviour of biological indicators of internal dose and some neuro-endocrine tests in aluminium workers.

The authors present the results of toxicological studies on aluminium from 1983 to 1988. In order to obtain reference values for serum and urine aluminium, 506 healthy adults, not occupationally exposed to the metal, residing in the Brescia area were studied. The following values were obtained: AlS = 5.8 +/- 2.9 micrograms/l; AlU 11.9 +/- 4.3 micrograms/l. The AlU and AlS values did not differ in relation to age, sex, alcohol consumption, smoking habits and residence, contrary to what has been found for some metals determined in the urine and/or blood of the same subjects. In a group of 227 subjects with occupational exposure to aluminium within the range 0.1-1.0 mg/m3, the mean levels of AlU were higher than that of the reference population; however the AlU of the workers were generally lower than 20 micrograms/l which is the upper limit for the reference population; 4 workers who were under treatment with antiacid preparations showed AlU values higher than 150 micrograms/l. Seven workers exposed to atmospheric aluminium concentrations around the TLV-TWA had higher AlU values at the end of their shift on all working days and on Friday morning the values where higher than those encountered on Monday morning. On the other hand no daily and weekly fluctuations were evident for AlS. For 14 workers the relationship between AlU and AlS values were examined in three subsequent periods after the start of working activity. Considering the same values of AlU, it was observed that the AlS increased with the duration of exposure. These results seem to indicate that AlU could be considered as indicator of current exposure and AlS as an indicator of cumulative exposure. Neuroendocrine tests were performed every 6 months in 21 workers after they had been hired. PRL and TSH values were reduced after 1 year of work and were still reduced 6 months later. Further analyses showed a different behaviour: in fact the levels of the two hormones rose above the reference values, while the HGH and other gonadotropins showed no alterations. These results seem to indicate that at the start of exposure to aluminium concentrations below TLV-TWA there is an effect on the hypothalamus-pituitary axis. This phenomenon is probably transient perhaps because of an adaptation mechanism. Further studies are however necessary to verify these results.

Interference of manganese on neuroendocrinal system in exposed workers. Preliminary report.

The neurotoxic effects of Manganese (Mn) are well known, and are usually caused by high occupational exposure over long periods of time. The effects caused by low doses of this metal have been poorly evaluated. For this reason, we decided to evaluate neuroendocrinal tests in a group of 14 male workers employed in a ferrous-manganese foundry (exposed to Mn air concentrations within the TLV-TWA) and in 14 male control subjects, by analyzing FSH, LH, prolactin, and cortisol. The urinary Mn; prolactin, and cortisol levels were significantly higher in the worker's group. The preliminary results of this research seem to show that for exposure below the TLV, Mn can somehow interfere with the neuroendocrine system. In order to confirm the existence of these effects and to verify their possible correlation with the dopaminergic control system, further studies are necessary.

Alteration of steroid hormone sulfation and D-glucaric acid excretion in lead workers.

The capability of lead to interfere with the first and/or second phase of enzymatic reaction of biotransformation has been investigated in ten lead workers and in ten controls by studying the steroid hormone sulfation and D-glucaric acid (GA) urinary excretion. No statistical differences have been found for the total amount of urinary steroids, whereas a decrease of about 50% was observed for the sulfated fraction in lead workers. The mean value for the GA excretion in the exposed subjects (1.8 +/- 0.7 mmol/mol creatinine) was significantly lower than in the control group (4.4 +/- 0.8 mmol/mol creatinine). In spite of the small number of investigated subjects, it can be hypothesized that an interaction of lead with sulfotransferase exists. The decreased GA excretion does not prove an altered activity of microsomal enzymes, although inhibition of microsomal activity following lead exposure was previously reported.

Steroid hormone sulphation in lead workers.

The metabolism of steroid hormones has been investigated in 10 workers exposed to lead and in 10 non-exposed subjects to determine whether lead interferes with the first or second phase reactions of steroid hormone biotransformation, or both. In the exposed workers blood lead concentrations (PbB) ranged from 45 to 69 micrograms/100 ml; in the controls PbB was less than 25 micrograms/100 ml. No statistical differences were found for the total amount of the urinary hormone metabolites, but a drop of about 50% was observed for the sulphated portion. It is suggested that lead interferes with the mechanisms of sulphoconjugation through an effect on the cytosol enzymes sulphotransferase and sulphokinase.

[Exposure to metals in dental laboratories]. / Esposizione a metalli nei laboratori odontotecnici.

Dental care includes handling of different types of metal alloys usually classified as "noble" and "base" in relation to the presence or absence of either gold or other precious metals. It must be born in mind that exposure to metals in this activities is due not only to those metals present in the alloys but also to those contained in the other materials used during the processes of casting and finishing. The most important metals are the following: Al, Be, Cd, Cr, Co, Cu, Au, In, Hg, Mo, Ni, Pd, Pt, Si, Ag, Sn, Ti, W, Zn. In this paper we investigated the environmental exposure to metals in dental laboratories studying the environmental air concentration of metals in casting and finishing processes estimating the "quality" of the elements present by Particle Induces X-ray Emission (PIXE) and the "quantity" of the elements by electro thermic atomic absorption spectrophotometry (ET-AAS) and the concentration of the main metals in the blood and in the urine of exposed technicians by ET-AAS. These analyses permitted to detect all the metals present in the work environment and to quantify their concentration, which always resulted to be low (except some metals during short time operations). The biological monitoring revealed the existence of moderate absorption of these metals in the exposed workers but it is not possible for us to affirm if this phenomenon represents a real risk for the health of the technicians. Hence further epidemiological and health surveillance investigations are needed to verify morbidity and mortality of the subjects employed in this activity.