Peripheral markers (Clara cell protein and alpha-glutathione S-transferase) and lipidoperoxidation (malondialdehyde) assessment in Sprague-Dawley rats instilled with haematite and benzo[a]pyrene

The literature suggests that the concomitant exposure to polycyclic aromatic hydrocarbons (PAH) and ferric oxide particles could enhance lung cancer incidence in environmental and occupational settings, High levels of tracheobronchial tumours were obtained in hamsters exposed to benzo[a]pyrene (B[a]P) adsorbed onto ferric oxide carrier particles, Therefore, we have assessed the toxic effects of exposure to haematite (Fe2O3) and B[a]P in male Sprague-Dawley rats, Animals were instilled with the chemicals alone (3 mg of Fe2O3 or B[a]P) or in combination (3 mg Fe2O3 + 3 mg B[a]P), Bronchoalveolar lavages (BAL) and biological samples (serum and urine) were collected 48 h after the intoxication, Clara cell protein (CC16) and alpha-glutathione S-transferase (alpha-GST), as peripheral markers of both tracheobronchial epithelial cell integrity and renal dysfunction, were determined in BAL fluid, serum and urine, Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in BAL fluid and serum, We observed a significant increase of CC16 concentrations in BAL fluid after Fe2O3+B[a]P instillation (p<0.05) in serum after Fe2O3 and Fe2O3+B[a]P exposure (p<0.01) and in urine after B[a]P administration (p<0.01). Instillation of Fe2O3 + B[a]P produced an increased amount of alpha-GST in BAL fluid (p<0.01), whereas B[a]P alone caused a significant elevation of or-GST in serum and urine (p<0.01), Moreover, Fe2O3 or Fe2O3 + B[a]P instillation induced a significant increase in MDA levels in BAL fluid (p<0.01 and p<0.05), In conclusion, Fe2O3 may have a low pulmonary toxicity. However, B[a]P manifested a rapid and high toxicity in the respiratory tract and kidneys, When B[a]P was adsorbed on haematite particles, both its retention in the respiratory tract and pulmonary toxicity increased. (C) 1998 John Wiley & Sons, Ltd

Urinary homovanillic acid and serum prolactin levels in children with low environmental exposure to lead

Current evidence suggests that the neurotoxic effects of lead may partially be mediated through interference with the dopaminergic system. The aim of this study was to assess the levels of two peripheral dopaminergic markers-serum prolactin (Pro-S) and urinary homovanillic acid (HVA-U)-in children living around two lead smelters, who are presumed to be exposed to high environmental lead pollution (n=200), and compare their results with 200 age- and sex-matched controls living in an area unpolluted by heavy metals, giving a total of 400 children (200 boys and 200 girls). The influence of lead exposure on HVA-U and Pro-S was assessed by stepwise multiple regression, testing lead concentrations in blood (Pb-B), age, sex and area of residence as predictors. Though lead levels were significantly higher in boys and in the lead-polluted environment, mean Pb-B values were relatively low, indicating a low uptake of lead in the contaminated environment (39.5 mug l(-1), range 4.6-165 mug l(-1), n=200), and no significant correlation could be found with either Pro-S or HVA-U. However, when the subgroup of 121 children with Pb-B levels above 50 mug l(-1) were considered, a weak positive correlation was found between Pb-B and HVA-U (r(2)=0.04, p=0.03), whilst in the even smaller subgroup of 15 children with Pb-B levels above 100 mug l(-1), Pro-S appeared to be positively correlated with Pb-B, though the numbers of children were too small for the correlation to reach statistical significance (p=0.095). These weak associations, probably not important in biological terms, indicate that Pro-S and HVA-U are not useful biomarkers at present exposure levels to lead in the environment. Nevertheless, the finding of subtle biochemical alterations in the dopaminergic system at Pb-B levels of around 100 mug l(-1) supports the recommended setting of the action level at this value

Biomarkers of renal effects in children and adults with low environmental exposure to heavy metals.

The health effects of chronic exposure to heavy metals such as lead, cadmium, and mercury are widely documented, yet few data exist about the renal impact of low environmental exposure to these metals, particularly in children. The aim of this study was to assess renal parameters in children and adults living in an environment known for its past heavy metal contamination around two nonferrous smelters in northern France (Noyelles-Godault and Auby) and to compare their results with age and gender-matched controls living in neighboring municipalities with unpolluted soil (total: 400 children, 600 adults, sex ratio = 1). The integrity of renal function was assessed by measuring the urinary excretion levels of total protein, albumin, transferrin, beta(2)-microglobulin, retinol-binding protein, brush border antigen, and the enzyme N-acetyl-beta-D-glucosaminidase (NAG). The mean blood concentrations of lead (Pb-B, children </=42.2 micro/L, adults </=71.3. micro/L) and of cadmium (Cd-B, children </=0.52 microg/L, adults 0.86 microg/L) were all relatively low, indicating a low uptake of these heavy metals from the environment despite relatively high levels in soil (between 100 and 1700 ppm for lead and 0.7 to 233 ppm for cadmium). Pb-B levels were, however, significantly increased in boys, girls, and women--but not men--living in the polluted area. Boys, men, and women living in the polluted area had also on average higher Cd-B levels. The concentrations of mercury in urine (Hg-U) were by contrast similar in control and exposed groups. None of the renal parameters studied showed a significant difference between control and exposed groups. The influence of heavy metals on renal parameters was further assessed by stepwise multiple regression, testing Pb-B, Cd-B, Hg-U, age, gender, body mass index (BMI), urinary creatinine levels, and area of residence as predictors in both children and adults, including first-order metal interaction terms, smoking habits, and alcohol consumption in adults. The only positive correlation was found between the urinary excretion of NAG activity (standardized for BMI and urinary creatinine) and Cd-B levels when taking the whole children population, indicating that even low cadmium burdens may produce subtle effects on the proximal tubule in children, although deleterious consequences are unlikely should exposure not increase. However, in the absence of other positive findings even after studying the smaller subgroups with higher levels of heavy metals, these results are clearly indicative of the minimal renal impact of living around nonferrous smelters that are currently complying with pollution regulations, even when soil contamination is still high