H Roels

An epidemiological re-appraisal of the association between blood pressure and blood lead: a meta-analysis.

Studies on the possible association between blood pressure and blood lead have reached divergent conclusions. In a previous meta-analysis, a doubling of the blood lead concentration was associated with a 1.0/0.6 mmu2009Hg increase in systolic and diastolic blood pressure (BP). This meta-analysis updates the analysis originally performed in 1994. Articles on the association between BP and blood lead were identified from computer searches from January 1980 to February 2001 using the Medical Literature Analysis and Retrieval System. Of the studies reviewed, 31 provided sufficient details to be considered. The meta-analysis included 58518 subjects recruited from the general population in 19 surveys and from occupationally exposed groups in 12 studies. In all but four studies, the results were adjusted for age, and most studies took into account additional confounding factors such as body mass index and the use of alcohol and medication. Weighted joint P-values were calculated using Stouffers procedure. The association between BP and blood lead was similar in both men and women. In the combined studies, a two-fold increase in blood lead concentration was associated with a 1.0 mmu2009Hg rise in the systolic pressure (95% CI +0.5 to +1.4 mmu2009Hg; P < 0.001) and with a 0.6 mmu2009Hg increase in the diastolic pressure (95% CI +0.4 to +0.8 mmu2009Hg; P < 0.001). On balance, this meta-analysis suggests that there can only be a weak association between BP and blood lead.

Urinary Cadmium and Lead Concentrations and Their Relation To Blood-pressure in a Population With Low Exposure

The 24 hour urinary excretion of cadmium (U-Cd) and lead (U-Pb), and the excretion of beta-2- microglobulins and retinol binding protein concentration in spot urines, were determined in a random 4% sample of the population of a small Belgian town. Blood pressure and body weight were measured on two separate occasions. U-Cd averaged 2.4 nmol/24 h in 46 youths, increased with age, and was significantly higher in 57 adult men as compared with 59 women (9.3 v 7.2 nmol/24 h; p less than 0.01). U-Pb averaged 28 nmol/24 h in youths and similarly increased with age: adult men excreted more lead than women (64 v 40.0 nmol/24 h; p less than 0.001). Among men, manual workers excreted more cadmium (12.6 v 7.5 nmol/24 h; p less than 0.05) but a similar amount of lead (62 v 61 nmol/24 h) compared with office workers. After adjusting for sex and age, U-Cd and U-Pb were not related to body weight and cigarette consumption. In simple regression analysis, U-Cd was positively correlated with both systolic (r = +0.30; p less than 0.05) and diastolic (r = +0.38; p less than 0.01) blood pressure in women. After adjusting for other contributing variables, however, a weak but negative relation became apparent between systolic pressure and U-Cd in women (t = -2.21; p = 0.033) and between diastolic pressure and U-Cd in men (t = -2.04; p = 0.047). In women urinary beta-2-microglobulin was related to diastolic pressure (r-0.44; p<0.01) and after adjusting for age to both systolic (t=2.75; p=0.009) and diastolic (t=-3.07; p=0.004) pressure. In none of the sex-age groups did U-Pb and retinol binding protein contribute to the blood pressure variability.

Comparative study of effect of inorganic lead and cadmium on blood δ-aminolevulinate dehydratase in man

Lauwerys, R. R., Buchet, J.-P., and Roels, H. A. (1973).British Journal of Industrial Medicine,30, 359-364. Comparative study of effect of inorganic lead and cadmium on blood δ-aminolevulinate dehydratase in man. δ-Aminolevulinate dehydratase (ALA1-D) of red blood cells, lead concentration in blood (Pb-B) and in urine (Pb-U), cadmium concentration in blood (Cd-B) and in urine (Cd-U), and ALA in urine (ALA-U) were measured in 77 workers occupationally exposed to cadmium, and in 73 control workers. An excellent negative correlation was found between log ALA-D and Pb-B (r = - 0·660) or Pb-U (r = - 0·501), but no significant correlation was found between Cd-B and log ALA-D activity. Unlike ALA-D, ALA-U is not correlated with Pb and Pb-U in the `normal range of Pb concentration investigated. Mean ALA-D activity in smokers is lower than in nonsmokers, and this is probably related to the fact that a higher mean Pb-B concentration is found in smokers than in nonsmokers. It is clear from this investigation that in the general population, and even in Cd-exposed workers, Cd has no significant effect on ALA-D. Moreover, all the available evidence indicates that ALA-D activity of erythrocytes is a very sensitive and specific parameter of lead in blood.

Comparison of in vivo effect of inorganic lead and cadmium on glutathione reductase system and delta-aminolevulinate dehydratase in human erythrocytes.

The activity of delta-aminolevulinate dehydratase (ALAD) of erythrocytes, the lead (Pb-B) and cadmium (Cd-B) concentration in whole blood, the content of reduced glutathion (GSH) in erythrocytes, and the regeneration rate of GSH by intact erythrocytes were measured during an epidemiological survey of 84 men employed in a Belgian cadmium and lead producing plant. A control group of 26 persons (students and laboratory staff) was also examined. The logarithm of the ALAD activity is highly inversely correlated with log Pb-B (r = -0.760) but no correlation was found with log Cd-B. There exists a significant negative correlation between GSH and log Pb-B (r = -0.423) but not between GSH AND LOG Cd-B. The apparently good relationship between log ALAD and GSH disappeared completely by holding log Pb-B constant, but log ALAD remained highly inversely correlated with log Pb-B when standardized for GSH concentration (r = -0.748). In vivo investigation of the GSH regeneration rate of intact erythrocytes demonstrated clearly that the overall activity of the glutathione oxidation-reduction pathways is not impaired in Pb and Cd-exposed workers with significantly increased Pb-B and Cd-B, since their initial GSH regeneration rate (first 15 minutes) was identical with that of the control group. Results of similar in vitro experiments in which control whole blood was incubated before-hand with Pb2+ or Cd2+, or both, reinforce this conclusion. Since increased Cd-B and Pb-B do not influence the glutathione reductase system of erythrocytes, and since endogenous erythrocyte GSH is not correlated with Cd-B, the moderate decrease in endogenous erythrocyte Gsh found in Pb-exposed workers might result from a Pb-induced impairment for the erythrocyte mechanism for glutathione synthesis.

Neurobehavioral performance in adolescents is inversely associated with traffic exposure

On the basis of animal research and epidemiological studies in children and elderly there is a growing concern that traffic exposure may affect the brain. The aim of our study was to investigate the association between traffic exposure and neurobehavioral performance in adolescents. We examined 606 adolescents. To model the exposure, we constructed a traffic exposure factor based on a biomarker of benzene (urinary trans,trans-muconic acid) and the amount of contact with traffic preceding the neurobehavioral examination (using distance-weighted traffic density and time spent in traffic). We used a Bayesian structural equation model to investigate the association between traffic exposure and three neurobehavioral domains: sustained attention, short-term memory, and manual motor speed. A one standard deviation increase in traffic exposure was associated with a 0.26 standard deviation decrease in sustained attention (95% credible interval: -0.02 to -0.51), adjusting for gender, age, smoking, passive smoking, level of education of the mother, socioeconomic status, time of the day, and day of the week. The associations between traffic exposure and the other neurobehavioral domains studied had the same direction but did not reach the level of statistical significance. The results remained consistent in the sensitivity analysis excluding smokers and passive smokers. The inverse association between sustained attention and traffic exposure was independent of the blood lead level. Our study in adolescents supports the recent findings in children and elderly suggesting that traffic exposure adversely affects the neurobehavioral function.

Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapour.

A significant reduction of kallikrein activity in urine (assayed by its amidolytic activity) was found in 64 normotensive workers who had been exposed to cadmium for 11 years on average and whose cadmium concentrations in urine ranged from 2.2 to 33.1 micrograms/g creatinine. The mean (geometric) urinary kallikrein activity (in U/g creatinine) amounted to 0.52 (range 0.11-1.90) in the control group (n = 193) against 0.39 (range 0.10-1.03) in the cadmium group, and the prevalence of abnormally low activity levels (less than or equal to 0.20 U/g creatinine) amounted to 17.2% in the cadmium group against 5.2% in the control group. A reduction of aldosterone release (aldosterone in urine) associated with an increased natriuresis was also observed. This might constitute a compensatory mechanism maintaining blood pressure in the normal range. These biological effects of cadmium were not reversible after removal from exposure. This study indicates that cadmium can induce an irreversible toxic effect in the distal nephron. It also suggests that an excessive cadmium body burden alone may not be sufficient to induce hypertension, but in individuals whose blood pressure regulation may be impaired by other factors cadmium could stimulate the development of hypertension. This study also supports the recommendation to prevent hypertensive subjects from being exposed to cadmium. There was no indication that moderate exposure to mercury vapour (n = 53; mercury in urine, range 11-224 micrograms/g creatinine; average duration of exposure: six years) or to inorganic lead (n = 23; lead in blood, range 40-67 micrograms/100 ml; average duration of exposure: eight years) was associated with a reduction of kallikrein production by the kidney.

Recent versus chronic exposure to particulate matter air pollution in association with neurobehavioral performance in a panel study of primary schoolchildren.

Childrens neuropsychological abilities are in a developmental stage. Recent air pollution exposure and neurobehavioral performance are scarcely studied. In a panel study, we repeatedly administered to each child the following neurobehavioral tests: Stroop Test (selective attention) and Continuous Performance Test (sustained attention), Digit Span Forward and Backward Tests (short-term memory), and Digit-Symbol and Pattern Comparison Tests (visual information processing speed). At school, recent inside classroom particulate matter ≤2.5 or 10μm exposure (PM2.5, PM10) was monitored on each examination day. At the childs residence, recent (same day up to 2days before) and chronic (365days before examination) exposures to PM2.5, PM10 and black carbon (BC) were modeled. Repeated neurobehavioral test performances (n=894) of the children (n=310) reflected slower Stroop Test (p=0.05) and Digit-Symbol Test (p=0.01) performances with increasing recent inside classroom PM2.5 exposure. An interquartile range (IQR) increment in recent residential outdoor PM2.5 exposure was associated with an increase in average latency of 0.087s (SE: ±0.034; p=0.01) in the Pattern Comparison Test. Regarding chronic exposure at residence, an IQR increment of PM2.5 exposure was associated with slower performances in the Continuous Performance (9.45±3.47msec; p=0.007) and Stroop Tests (59.9±26.5msec; p=0.02). Similar results were obtained for PM10 exposure. In essence, we showed differential neurobehavioral changes robustly and adversely associated with recent or chronic ambient exposure to PM air pollution at residence, i.e., with recent exposure for visual information processing speed (Pattern Comparison Test) and with chronic exposure for sustained and selective attention.

Risk of cancer and environmental exposure to cadmium in a prospective population study

Katholieke Univ Leuven, Louvain, Belgium. Univ Hasselt, Hasselt, Belgium. Univ Louvain, Brussels, Belgium.

Placental DNA methylation as a proxy for fetal neurodevelopment and sex-specific associations with in utero particulate air pollution.

Background and aims Exposure to particulate matter (PM) air pollution during pregnancy may affect human fetal development. Epigenetic mechanisms are believed to play an essential role in the developmental changes during early life. Within the ENVIRONAGE birth cohort, we investigated whether in utero exposure to PM is associated with differences in placental DNA methylation of genes involved in early neurodevelopment, i.e., Brain-Derived Neurotrophic Factor (BDNF), Leptin (LEP) and 5Hydroxytryptamine (serotonin) receptor 2A (HTR2A).

Placental nitrosative stress and in utero exposure to particulate matter

Background and aims A wide variety of adverse health effects on both fetuses and neonates have been ascribed to particulate matter (PM) air pollution. Recent evidence suggests that PM exposure results in increased oxidative and nitrosative stress. In the ENVIRONAGE birth cohort, we investigated the association of placental 3-nitrotyrosine (3-NT) with PM exposure during various time windows of pregnancy.