Lars Jarup

Current status of cadmium as an environmental health problem

Cadmium is a toxic metal occurring in the environment naturally and as a pollutant emanating from industrial and agricultural sources. Food is the main source of cadmium intake in the non-smoking population. The bioavailability, retention and toxicity are affected by several factors including nutritional status such as low iron status. Cadmium is efficiently retained in the kidney (half-time 10-30 years) and the concentration is proportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can also cause bone damage, either via a direct effect on bone tissue or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular injury may progress to glomerular damage with decreased glomerular filtration rate, and eventually to renal failure. Furthermore, recent data also suggest increased cancer risks and increased mortality in environmentally exposed populations. Dose-response assessment using a variety of early markers of kidney damage has identified U-Cd points of departure for early kidney effects between 0.5 and 3 microg Cd/g creatinine, similar to the points of departure for effects on bone. It can be anticipated that a considerable proportion of the non-smoking adult population has urinary cadmium concentrations of 0.5 microg/g creatinine or higher in non-exposed areas. For smokers this proportion is considerably higher. This implies no margin of safety between the point of departure and the exposure levels in the general population. Therefore, measures should be put in place to reduce exposure to a minimum, and the tolerably daily intake should be set in accordance with recent findings.

Urban air pollution and lung cancer in Stockholm.

We conducted a population-based case-control study among men 40–75 years of age encompassing all cases of lung cancer 1985–1990 among stable residents of Stockholm County 1950–1990. Questionnaires to subjects or next-of-kin (primarily wives or children) elicited information regarding smoking and other risk factors, including occupational and residential histories. A high response rate (>85%) resulted in 1,042 cases and 2,364 controls. We created retrospective emission databases for NOx/NO2 and SO2 as indicators of air pollution from road traffic and heating, respectively. We estimated local annual source-specific air pollution levels using validated dispersion models and we linked these levels to residential addresses using Geographical Information System (GIS) techniques. Average traffic-related NO2 exposure over 30 years was associated with a relative risk (RR) of 1.2 (95% confidence interval 0.8–1.6) for the top decile of exposure, adjusted for tobacco smoking, socioeconomic status, residential radon, and occupational exposures. The data suggested a considerable latency period; the RR for the top decile of average traffic-related NO2 exposure 20 years previously was 1.4 (1.0–2.0). Little association was observed for SO2. Occupational exposure to asbestos, diesel exhaust, and other combustion products also increased the risk of lung cancer. Our results indicate that urban air pollution increases lung cancer risk and that vehicle emissions may be particularly important.

Low level exposure to cadmium and early kidney damage: the OSCAR study

OBJECTIVES To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. METHODS Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (α1-microglobulin) in urine to assess tubular proteinuria. RESULTS There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. CONCLUSION Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.

Using Geographic Information Systems for Exposure Assessment in Environmental Epidemiology Studies

Geographic information systems (GIS) are being used with increasing frequency in environmental epidemiology studies. Reported applications include locating the study population by geocoding addresses (assigning mapping coordinates), using proximity analysis of contaminant source as a surrogate for exposure, and integrating environmental monitoring data into the analysis of the health outcomes. Although most of these studies have been ecologic in design, some have used GIS in estimating environmental levels of a contaminant at the individual level and to design exposure metrics for use in epidemiologic studies. In this article we discuss fundamentals of three scientific disciplines instrumental to using GIS in exposure assessment for epidemiologic studies: geospatial science, environmental science, and epidemiology. We also explore how a GIS can be used to accomplish several steps in the exposure assessment process. These steps include defining the study population, identifying source and potential routes of exposure, estimating environmental levels of target contaminants, and estimating personal exposures. We present and discuss examples for the first three steps. We discuss potential use of GIS and global positioning systems (GPS) in the last step. On the basis of our findings, we conclude that the use of GIS in exposure assessment for environmental epidemiology studies is not only feasible but can enhance the understanding of the association between contaminants in our environment and disease.

Risk of adverse birth outcomes in populations living near landfill sites

Abstract Objective: To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. Design: Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. Setting: Great Britain. Subjects: Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). Main outcome measures: All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). Results: For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. Conclusions: We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various possibilities. What is already known on this topic Various studies have found excess risks of certain congenital anomalies and low birth weight near landfill sites Risks up to two to three times higher have been reported These studies have been difficult to interpret because of problems of exposure classification, small sample size, confounding, and reporting bias What this study adds Some 80% of the British population lives within 2 km of known landfill sites in Great Britain By including all landfill sites in the country, we avoided the problem of selective reporting, and maximised statistical power Although we found excess risks of congenital anomalies and low birth weight near landfill sites in Great Britain, they were smaller than in some other studies Further work is needed to differentiate potential data artefacts and confounding effects from possible causal associations with landfill

Hypertension and exposure to noise near airports: the HYENA study.

Background An increasing number of people are exposed to aircraft and road traffic noise. Hypertension is an important risk factor for cardiovascular disease, and even a small contribution in risk from environmental factors may have a major impact on public health. Objectives The HYENA (Hypertension and Exposure to Noise near Airports) study aimed to assess the relations between noise from aircraft or road traffic near airports and the risk of hypertension. Methods We measured blood pressure and collected data on health, socioeconomic, and lifestyle factors, including diet and physical activity, via questionnaire at home visits for 4,861 persons 45–70 years of age, who had lived at least 5 years near any of six major European airports. We assessed noise exposure using detailed models with a resolution of 1 dB (5 dB for United Kingdom road traffic noise), and a spatial resolution of 250 × 250 m for aircraft and 10 × 10 m for road traffic noise. Results We found significant exposure–response relationships between night-time aircraft as well as average daily road traffic noise exposure and risk of hypertension after adjustment for major confounders. For night-time aircraft noise, a 10-dB increase in exposure was associated with an odds ratio (OR) of 1.14 [95% confidence interval (CI), 1.01–1.29]. The exposure–response relationships were similar for road traffic noise and stronger for men with an OR of 1.54 (95% CI, 0.99–2.40) in the highest exposure category (> 65 dB; ptrend = 0.008). Conclusions Our results indicate excess risks of hypertension related to long-term noise exposure, primarily for night-time aircraft noise and daily average road traffic noise.

Low-level cadmium exposure and osteoporosis

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long‐term low‐level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16–81 years, environmentally or occupationally exposed to cadmium, using dual‐energy X‐ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose‐response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose‐response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0‐4.8) in the dose group 0.5‐3 nmol Cd/mmol creatinine and 5.3 (2.0‐14) in the highest dose category (≥3 nmol/mmol creatinine) compared with the lowest dose group (<0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65‐5.3) in the dose group 0.5‐3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.

Increased prevalence of hypertension in a population exposed to aircraft noise

OBJECTIVES To investigate whether there is a relation between residential exposure to aircraft noise and hypertension. METHODS The study population comprised two random samples of subjects aged 19–80 years, one including 266 residents in the vicinity of Stockholm Arlanda airport, and another comprising 2693 inhabitants in other parts of Stockholm county. The subjects were classified according to the time weighted equal energy and maximum aircraft noise levels at their residence. A questionnaire provided information on individual characteristics including history of hypertension. RESULTS The prevalence odds ratio for hypertension adjusted for age, sex, smoking, and education was 1.6 (95% confidence interval (95% CI) 1.0 to 2.5) among those with energy averaged aircraft noise levels exceeding 55 dBA, and 1.8 (95% CI 1.1 to 2.8) among those with maximum aircraft noise levels exceeding 72 dBA. An exposure-response relation was suggested for both exposure measures. The exposure to aircraft noise seemed particularly important for older subjects and for those not reporting impaired hearing ability. CONCLUSIONS Community exposure to aircraft noise may be associated with hypertension. Main messages Exposure to aircraft noise may be a risk factor for hypertension. It is suggested that special attention be paid to maximum noise levels because of possible physiological effects from aircraft noise.

Creatinine versus specific gravity-adjusted urinary cadmium concentrations.

Abstract The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20–50 years (24-h urine samples); (2) 289 men and 434 women aged 16–81 years (spot urine samples); and (3) 98 men and 105 women aged 19–72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15–92% higher in women or older individuals than in men or younger individuals. Women or older individuals had –3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.

Acute effects of night-time noise exposure on blood pressure in populations living near airports

AIMS Within the framework of the HYENA (hypertension and exposure to noise near airports) project we investigated the effect of short-term changes of transportation or indoor noise levels on blood pressure (BP) and heart rate (HR) during night-time sleep in 140 subjects living near four major European airports. METHODS AND RESULTS Non-invasive ambulatory BP measurements at 15 min intervals were performed. Noise was measured during the night sleeping period and recorded digitally for the identification of the source of a noise event. Exposure variables included equivalent noise level over 1 and 15 min and presence/absence of event (with LAmax > 35 dB) before each BP measurement. Random effects models for repeated measurements were applied. An increase in BP (6.2 mmHg (0.63-12) for systolic and 7.4 mmHg (3.1, 12) for diastolic) was observed over 15 min intervals in which an aircraft event occurred. A non-significant increase in HR was also observed (by 5.4 b.p.m.). Less consistent effects were observed on HR. When the actual maximum noise level of an event was assessed there were no systematic differences in the effects according to the noise source. CONCLUSION Effects of noise exposure on elevated subsequent BP measurements were clearly shown. The effect size of the noise level appears to be independent of the noise source.