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Biomedical subjects

P Grandjean

Publications and source records attributed to P Grandjean.

At least 19 recordsLinked to original sources
PubMed1992

Cancer incidence and mortality in workers exposed to fluoride.

BACKGROUND: Although a recent bioassay showed increased frequency of bone cancer in rats with high oral intake of fluoride, the data are reported as equivocal evidence of carcinogenicity. In humans, occupational fluoride exposure may cause skeletal fluorosis, and our earlier follow-up of fluoride-exposed workers showed increased incidence of respiratory cancers. PURPOSE: To further evaluate occupational fluoride exposure as a carcinogenic risk factor, we extended by approximately one decade the follow-up of a cohort of 425 men and 97 women employed for at least 6 months in the period 1924-1961 at the Copenhagen cryolite processing plant. Cryolite ore contains about 50% fluoride. METHODS: Cancer mortality was determined for the period 1941-1989, and incidence for 1943-1987. For comparison, we used national mortality rates and cancer incidence rates for the Copenhagen area. RESULTS: Among the men, 300 deaths occurred; 223 were expected. Respiratory (lung and laryngeal) cancers and violent death were responsible for most of this excess; rates for mortality from cardiovascular disease were close to the rates expected. Of the 423 male workers, 119 developed cancers; 103.6 were expected. There was excess incidence of cancers of the lungs (35 men; standard incidence ratio [SIR] = 1.35), larynx (5 men; SIR = 2.29), and urinary bladder (17 men; SIR = 1.84). Maximum incidence occurred after 10-19 years of employment, but otherwise, no stable relationship between cancer incidence and duration of employment was observed. The incidence of respiratory and urinary cancers was particularly high in men less than 35 years old at first employment. Cancers in female workers were too few to allow detailed evaluation. CONCLUSIONS: The increased incidence of respiratory cancers suggests that cigarette smoking was frequent in this cohort, despite the unremarkable cardiovascular mortality, but the disproportionate increase in the incidence of bladder cancer is difficult to explain by smoking habits alone. Because this industrial cohort was exposed to high concentrations of fluoride dust, heavy respiratory exposure to fluoride may have contributed to the increased cancer risk. If these workers inhaled a carcinogenic substance partly excreted in the urine, an increased incidence of respiratory and bladder cancers would not be inconceivable. IMPLICATION: The potential role of fluoride as a cause of bladder cancer needs to be explored.

Adult↗
PubMed1992

The ICOH and IUPAC international programme for establishing reference values of metals.

In cooperation with the ICOH Scientific Committee on the Toxicology of metals and IUPAC Commission on Toxicology, we have developed evaluation criteria for derivation of reference values for metal concentrations in human tissues and fluids. In a first attempt to illustrate how these criteria may be used, tentative reference values for mercury in human blood were derived. For persons who do not eat fish, a mean value of 10 mumol/1 (2 micrograms/1) was suggested. It was pointed out, however, that this value was based on information that did not meet the desired quality requirements, which, unfortunately were not met by any of the published reports.

Animals↗
PubMed1992

Individual susceptibility to toxicity.

Individual variation in susceptibility to chemical toxicity may be due to differences in toxicokinetic patterns or effect modification. Well-documented interspecies genetic differences in susceptibility to chemicals had lead to studies of such variation also within species. Epidemiological evidence now suggests that common variations, particularly in the P-450 enzymes, may play a major role in determining individual susceptibility to chemically-induced disease. Physiologic factors are involved in the particular susceptibility of the fetus, the newborn, and the old. Constitutional susceptibility is also affected by acquired conditions, including chronic disease, such as diabetes mellitus. Perhaps the most complex area relates to the increase in vulnerability caused by previous or contemporary exposure to other factors, thus eliciting, e.g., synergistic effects. Although amply demonstrated by experimental studies, epidemiological or clinical confirmation is generally lacking. One hypothesis suggests that a chemical exposure may affect the reserve capacity of the body, though not resulting in any immediate adverse effect. Subsequently, the body becomes unable to compensate for an additional stress, and toxicity then develops. Epidemiological approaches are available and need to be expanded. Research in this area has potential ethical implications which should be dealt with in an open, informed forum.

Age Factors↗
PubMed1992

Reference intervals for trace elements in blood: significance of risk factors.

A random sample of 100 men and 100 women was examined for whole-blood concentrations of mercury, lead, cadmium and selenium, and the serum concentrations of selenium, nickel, fluoride, aluminium, zinc and copper. Major predictors were sex, hormonal factors (pregnancy, menopause, use of oral contraceptives), age, tobacco smoking and alcohol drinking. Among notable associations, increased blood-mercury was related to the presence of more than four amalgam fillings in the teeth. Blood-mercury correlated with blood-selenium, but a relation to fish intake could only be demonstrated for the former parameter. In women, blood-lead appeared to increase with age, with the highest levels seen after the menopause. Serum-nickel was slightly lower in patients with nickel-related contact eczema. Only the selenium concentrations showed a slight increase in individuals taking mineral supplements. Serum-zinc concentrations decreased considerably during the day. Thus, due to the substantial influence of physiological and environmental factors, individual results must be interpreted in the light of the known predictors for the trace element concentration. However, population-based reference intervals for trace elements in blood are useful to explore geographic and temporal variations.

Adult↗
PubMed1991

[Treatment of chronic occupational lead poisoning with dimercaptosuccinic acid (DMSA)].

2,3-dimercaptosuccinic acid (DMSA) mobilizes lead from superficial depots. In comparison with other chelating agents, DMSA has a high therapeutic index and has the additional advantage that it can be administered orally. We have used DMSA for treatment of chronic occupational lead poisoning in a 54-year old male with signs of neurotoxic effects. The treatment resulted in a rapid decrease in the blood-lead concentration, followed by a slow increase after the treatment and subsequent stabilization at a blood-lead level lower than prior to treatment. During the first course of treatment, almost 100 mumols lead was excreted in the urine. As a result of successive courses of treatments, the patient's condition was improved. However, during the third course of treatment, he developed a mucocutaneous rash which faded again after withdrawal of DMSA; this reaction was subsequently provoked by sub-therapeutic doses, and continued treatment was therefore cancelled. Only minor, reversible side effects of DMSA have hitherto been reported, and DMSA must therefore be regarded a promising agent for long-term, out-patient chelation treatment of chronic lead poisoning.

Humans↗
PubMed1991

[Mortality among filling station attendants].

At the Danish census on 9 November 1970, 4,055 men and 1,195 women aged 20-64 years indicated an employment that was coded as retail sale of oil and petrol; almost all individuals probably worked as petrol station attendants. Record linkage at Danmarks Statistik showed that 529 men had died during the following 17 years. Respiratory cancer (75 deaths) was the only cause of death that showed a significant excess (standardized mortality ratio, 1.58; 95% confidence interval, 1.25-2.00) when compared to all men gainfully employed at the time of the census. An increased mortality due to the group of cardiovascular disease could not be related to any particular subgroup. The mortality in women did not differ from expected rates. These results are in accordance with data from other countries on occupational groups exposed to high concentrations of exhaust fumes.

Adult↗
PubMed1991

Effects on reserve capacity: significance for exposure limits.

The human body has a certain capacity to withstand potentially adverse effects of environmental exposures. Chemical exposures may result in a weakening of the body defenses, i.e. a decrease in reserve capacity, thus leading to increased susceptibility to other exposures. Thus, despite normal hematological findings in the initial examination of a group of lead-exposed workers, the lead exposure caused a decreased reserve capacity for blood formation; these effects became prominent only after phlebotomy where the lead-exposed workers showed a decreased rate of blood regeneration. Evidence from studies of cell attrition and age-related functional decreases of the nervous system and the kidneys suggest that a reserve capacity exists and that it may be vulnerable to chemical exposures. Reserve capacity may therefore be a notion of wide significance with regard to chemical exposures as part of multicausal disease etiologies.

Case-Control Studies↗
PubMed1991

Lung cancer in filling station attendants.

At the Danish census on 9 November 1970, 4,055 men and 1,195 women aged 20-64 years indicated an employment that was coded as retail sale of oil and gasoline; almost all individuals probably worked as filling station attendants. Record linkage at Danmarks Statistik showed that 529 of the men had died during the following 17 years. Respiratory cancer (75 deaths) was the only cause of death that showed a significant excess (standardized mortality ration, 1.58; 95% confidence interval, 1.25-2.00) when compared to all men gainfully employed at the time of the census. An increased mortality due to cardiovascular disease could not be related to any particular diagnostic subgroup; the mortality in women did not differ from expected rates. These results are in accordance with data from other countries on occupational groups exposed to high levels of exhaust fumes.

Adult↗
PubMed1991

Chronic lead poisoning treated with dimercaptosuccinic acid.

A 54-year-old male with chronic lead poisoning was treated with 2.3-dimercaptosuccinic acid (DMSA). A daily dosage of 30 mg/kg body weight for three days and 20 mg/kg for four days resulted in a decrease of the blood-lead concentration (B-Pb) from 3.7 to 0.7 mumol/l; the total amount of lead excreted in the urine during the first seven 24 hr periods was 75 mumol. After the treatment, B-Pb slowly increased to 3.3 mumol/l. A second treatment was then initiated and resulted in similar changes in B-Pb. However, during the third treatment, the patient developed a mucocutaneous vesicular flare; the eruptions faded after cessation of the chelation therapy, but could be provoked by DMSA doses of 10 mg/kg and above. Despite the small number of treatment courses, the patient showed obvious mental improvement and reported less headache and improved memory. Thus, DMSA is an efficient chelator that results in a rapid, though temporary decrease in B-Pb. Although oral treatment with this chelator may be supervised from the out-patient clinic, careful monitoring for potential side effects is recommended.

Chelation Therapy↗
PubMed1991

Temporal and interindividual variation in erythrocyte zinc-protoporphyrin in lead exposed workers.

Nineteen male workers from a factory making lead batteries participated in monthly blood tests to follow the effects of decreasing exposures to lead. The overall average blood lead (B Pb) concentration was 1.95 mumol/l (40 micrograms/100 ml), but a significant decrease was seen over the one year study period. The relation to erythrocyte zinc-protoporphyrin (ZPP) concentration showed considerable scatter and only marginal improvement of the relation was obtained when each ZPP result was compared with the average B Pb concentration during the previous four months. On an individual basis, five men showed a considerable decline in ZPP following decreases in B Pb concentration. In five other subjects with similar decreases in B Pb, no change in ZPP concentration was seen. These two groups were similar with regard to haemoglobin concentration, initial B Pb concentration, and age, but differed in duration of exposure. A longer exposure time and presumably, therefore, larger body burdens of lead seemed to prevent the expected decrease in erythrocyte ZPP.

Adult↗
PubMed1991

Non-specificity of clinical signs and symptoms caused by environmental chemicals.

1. A review of the scientific literature revealed that 220 environmental chemicals had caused documented systemic toxicity in humans. This number is relatively small compared to the large number of industrial chemicals in the environment. 2. A total of 149 of these chemicals were verified as neurotoxins, thus emphasizing the sensitivity of this target organ. Despite the exclusion of chemicals that cause airway irritation only, 99 chemicals caused adverse effects on the respiratory system. Toxicity to the liver, kidneys and blood forming organs was less frequent. 3. Most of the individual clinical effects had a very low specificity in cases of human intoxication. Of 80 major signs and symptoms, 17 had only a single documented chemical aetiology. However, the combination of two or more signs or symptoms was found to provide an improved guidance to aetiological diagnosis. The paucity of specific signs and symptoms is probably one of the reasons that only 220 environmental chemicals have been documented as causes of human disease.

Environmental Exposure↗
PubMed1991

Lessons from a Danish study on neuropsychological impairment related to lead exposure.

Serious problems emerge when evaluating evidence on lead neurotoxicity in children. The extent of these problems and ways to control them were explored in a study of 1291 children from the first class in the schools of Aarhus municipality, Denmark. The lead retention in circumpulpal dentin in shed deciduous teeth was used as an indicator of cumulated lead exposure; it correlated most strongly with traffic density at the residence of each family and at the day-care institutions. In a nested case-control group selected on the basis of dentin lead concentrations, 29 of 200 children had encountered obstetrical complications and other medical risks for neurobehavioral dysfunction; these children primarily belonged to the low-lead group. As lead-related neurobehavioral effects are nonspecific, inclusion of these children in the data analysis would therefore have distorted the results toward the null hypothesis. Children from the high-lead group who had experienced neonatal jaundice showed impaired performance when compared to other high-lead children; this finding may suggest a synergistic effect. The Bender gestalt test scored by the Göttingen system was the test that was most sensitive to lead exposure. The conclusion that neurobehavioral effects can be caused by the relatively low lead exposures in Denmark may not be surprising, as current exposures to this toxic metal greatly exceed the prepollution levels to which the human body originally adapted.

Absorption↗
PubMed1991

Lead concentration in deciduous teeth from Danish school children.

Deciduous teeth were collected from school children in the first grade in six Danish municipalities; 2,033 teeth were received from 1,848 children. The geometric mean for the largest group (from Arhus) was 8.4 micrograms/g. The lead concentrations were similar in two Copenhagen suburbs with a secondary lead and a lead battery factory (geometric means, 9.6 and 9.9 micrograms/g, respectively). Increased lead concentrations were seen in children of low social class, in those whose fathers were automechanics or shipyard workers. Another part of the study showed that children residing in areas with heavy traffic also were at risk for increased lead retention. Thus, automobile exhausts and indirect occupational exposure appear to be important sources of lead retention in children, while a contribution from industrial emissions could not be detected.

Child↗
PubMed1990

[Risk of high copper content in drinking water].

Copper occurs in small amounts in certain food items, but toxic exposures in Northern Europe have occurred only in connection with contaminated drinking water. Chronic exposure of small children can result in development of Indian Childhood Cirrhosis. This disease has recently been documented in Germany as a result of drinking water contaminated from corrosion of water pipes made of copper. Continued diarrhoea in small children can also be due to high copper exposure. Copper is not routinely determined in drinking water in Denmark. Further, no central registration is available concerning water with low pH or the types of water pipes used in houses.

Child↗
PubMed1990

Predictors of tooth-lead level with special reference to traffic. A study of lead-exposure in children.

Possible predictors of the lead burden of children were investigated in a low-exposure area. A total of 1302 school children in the first form within the municipality of Aarhus, Denmark, donated deciduous teeth for determination of the lead concentration in the circumpulpal dentin. The families were interviewed on possible sources of lead. Present and former addresses of residences and day-care institutions were obtained, and the traffic intensity was estimated at each of these addresses. Children with a high lead burden resided significantly more often in heavily-travelled streets than children with a low burden, but only during their first 3 years of life. The increased risk for a high lead burden was related to the traffic intensity in a dose-response manner. Further, children with a high lead burden more often exhibited pica, their mothers smoked more during pregnancy, and their fathers were more likely to work at a garage or shipyard. In a logistic multivariate regression, such parental occupation increased the risk for a high lead burden 1.5-fold (ORadj; P = 0.03), whereas tobacco and traffic each were of borderline significance (ORadj = 1.4, P = 0.08).

Air Pollutants↗