B4. A study on how to prevent the toxic effects of cadmium in the population at large

Setting: The PheeCad study is a longitudinal population study, which inves-ti-gated the health effects of environmental exposure to cadmium and lead. The participants constituted a random sample of the popu-lation of two areas, cho-sen in or-der to provide a wide range of environmental exposure to cadmium.

Transfer of cadmium: The transfer of cadmium was investigated in 230 subjects (age range: 20-83 years), who consumed vegetables grown in kitchen gardens on a sandy acidic soil (mean pH ± 6.3). The study investigated the association between the cadmium lev-els in blood and urine and the cadmium concentration in the soil (range: 0.2 - 44 ppm). Seventy-six subjects were current smokers and 122 participants lived in a district with known cadmium pollution. Urinary cadmium in the 230 subjects averaged 8.7 nmol/24-h (range: 1.3 to 47 nmol/24-h) and was after adjustment for age positively correlated with the cadmium level in the soil; a two-fold increase of the soil concentration was accompanied by a 7% rise in urinary cadmium in men (r² = 0.05; p = .04) and by a 4% rise in women (r² = 0.02; p = .05).

In conclusion, in a rural population, consuming veg-etables grown on a sandy acidic soil, 2 to 4% of the vari-ance of urinary cadmium was directly related to the cadmium level in the soil.

Glomerular and tubular dysfunction related to cadmium exposure: The PheeCad study also explored whether across 10 land areas with differing cadmium pollution an association could be demonstrated between glomerular and tubular renal function and the internal (in urine) and external (in the environment) cadmium doses. Cadmium was measured in the soil and in vegetables in 10 districts, six of which bordered on non-ferrous smelters. Renal function and the concentrations of metals in blood and urine were measured in 703 randomly selected residents (response rate: 78%). The six polluted areas, compared with the four other districts, showed higher cadmium levels in the soil (4.86 vs. 0.81 ppm) and in locally grown vegetables, such as celery (2.43 vs. 0.68 ppm) and beans (0.42 vs. 0.15 ppm). Residents from the polluted areas had a raised urinary cadmium (10.5 vs. 7.9 nmol/24-h) and copper (0.16 vs. 0.14 µmol/24-h), higher serum creatinine (100 vs. 97 µmol/l) and elevated urinary excretions of ß₂-microglobulin (109 vs. 95 µg/24-h), retinol-binding-protein (136 vs. 118 µg/24 h) and N-acetyl-ß-glucosaminidase (1.78 vs. 1.38 U/24-h).

The creatinine clearance (87 vs. 92 ml/min) was reduced in the six polluted areas. Across the 10 districts, cadmium in the soil was positively correlated with cadmium in celery (r = 0.77), in beans (r = 0.67) and in the residents' urine (r = 0.76). The creatinine clearance was inversely correlated with cadmium in the soil (r = -0.78), in celery (r = -0.90) and in beans (r = -0.70). The correlations across the 10 areas between the cadmium doses and the excretion of microproteins and N-acetyl-ß-glucosaminidase were positive, but tended to be weaker than those observed with the creatinine clearance.

In conclusion, the past emissions from non-ferrous smelters gave rise to persistent contaminants in the environment, such as cadmium, which permeate into the food chain. These contaminants create the potential for exposure of the general population, leading to mild renal dysfunction and alterations in the zinc and copper homeostasis.

Exposure to inorganic arsenic: The exposure of the population to inorganic arsenic, a known carcinogen, was assessed in Belgium by measuring the 24-h urinary arsenic excretion in the CadmiBel (1985-1989) and PheeCad (1991-1995) surveys. In the former study measurements were obtained in industrialized urban areas (Liège: n = 664, Charleroi: n = 291), in a rural control area (Hechtel-Eksel: n = 397) and in rural districts, in which the population had possibly been exposed via the emissions of nonferrous smelters (Western Noorderkempen: n = 93, Eastern Noorderkempen: n = 244). The CadmiBel results showed that after adjustment for gender, age and body mass index, the 24-h arsenic excretion in the Liège area (91 nmol) was lower (p<.001) than in Charleroi (155 nmol), Hechtel-Eksel (144 nmol) and the Western Noorderkempen (158 nmol), whereas the highest 24-h excretion was observed in the Eastern Noorderkempen (455 nmol). From 1991 to 1995, the rural areas (n = 609) were re-examined, together with an urban control area (Leuven, n = 152). In this period, the adjusted 24-h urinary arsenic excretion in the rural areas (Hechtel-Eksel 99 nmol; Western and Eastern Noorderkempen 97 nmol) was lower than six years earlier and similar to the excretion Leuven (108 nmol). Longitudinal observations in 529 people residing in the rural areas showed that their 24-h urinary arsenic excretion decreased (p<.001) from 222 to 100 nmol.

In conclusion, industry was identified as the most likely source of the increased exposure in the Eastern Noorderkempen from 1985 to 1989, (1) because the urinary arsenic excretion did not follow the regional differences in the arsenic content of the drinking water, (2) because an increased exposure was only observed down wind from the industrial sites, (3) because in individual subjects the urinary arsenic excretion was inversely correlated with the distance to the nearest smelter (4) and because the fall in the urinary arsenic excretion over time was accompanied by a decrease in the industrial activity.

An important observation was that the official network monitoring the arsenic concentration in airborne and precipitating dust, did not detect the increased exposure in the Eastern Noorderkempen between 1985 to 1989. These findings highlight the necessity of validating environmental monitoring programs by directly estimating the internal exposure of the population.

Lead exposure and blood pressure in a longitudinal survey: In order to re-evaluate in a prospective fashion the association between low-level lead exposure and blood pressure, a random population sample was studied in Belgium in 1985-1989 (n = 728; 49% men; age range, 20-82 years) and re-examined in 1991-1995. At baseline and follow-up, blood pressure was measured by conventional sphygmomanometry (15 readings in total) and at follow-up also by 24-h ambulatory monitoring. Exposure was estimated from lead and zinc protoporphyrin in blood. Multivariate analyses allowed for gender, age, body mass index, smoking and drinking habits, physical activity, exposure at work, social class, menopausal status, intake of medications, hematocrit and serum calcium and g-glutamyltransferase. At baseline the conventional blood pressure averaged (systolic/diastolic ± SD) 130±17/77±9 mm Hg, blood lead 0.42 µmol/l (range: 0.08-3.50) and zinc protoporphyrin 1.0 µg/g hemoglobin (0.3-19.5). Over the 5.2 year (median) follow-up, lead dropped (p<.001) by 0.14 µmol/l (32%). Small but significant (p<.01) changes occurred in the conventionally measured systolic (-1.5 mm Hg) and diastolic (+1.7 mm Hg) blood pressures and in zinc protoporphyrin (+0.5 µg/g hemoglobin). Over follow-up, no consis-tent associations emerged between the changes in the conventional blood pressure and in blood lead or zinc protoporphyrin. In addition, blood lead or zinc protoporphyrin at baseline did not predict the development of hypertension in 47 patients (risk ratio associated with a doubling of the ini-tial blood lead concentration: 1.2; CI: 0.7-2.0). In a time-integrated analysis, in which each person was characterized by all available measurements, the conventional blood pressure did not correlate with blood lead and zinc protoporphyrin concentrations.

Similarly, the 24-h blood pressure at follow-up, which averaged 119±11/71±8 mm Hg (n = 684), did not show a consistent relation with blood lead or zinc protoporphyrin at base-line or at follow-up. Lead exposure, at the intensity studied, was not associated with increased conventional or 24-h blood pressures in the general population or with an increased risk of hypertension.