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Biomedical subjects

Philippe Grandjean

Publications and source records attributed to Philippe Grandjean.

At least 37 records · Page 2Linked to original sources
PubMed2005

Application of hair-mercury analysis to determine the impact of a seafood advisory.

Following an official recommendation in the Faroe Islands that women should abstain from eating mercury-contaminated pilot whale meat, a survey was carried out to obtain information on dietary habits and hair samples for mercury analysis. A letter was sent to all 1180 women aged 26-30 years who resided within the Faroes, and the women were contacted again 1 year later. A total of 415 women responded to the first letter; the second letter resulted in 145 repeat hair samples and 125 new responses. Questionnaire results showed that Faroese women, on average, consumed whale meat for dinner only once every second month, but the frequency and meal size depended on the availability of whale in the community. The geometric mean hair-mercury concentration at the first survey was higher in districts with available whale than in those without (3.03 vs. 1.88 microg/g; P=0.001). The mercury concentration also depended on the frequency of whale meat dinners and on the consumption of dried whale meat. The 36 women who did not eat whale meat at all had a geometric mean hair-mercury concentration of 1.28 microg/g. At the time of the second survey, the geometric mean had decreased to 1.77 microg/g (P<0.001), although whale was now available in all districts. In comparison with previously published data on hair-mercury concentrations in pregnant Faroese women, these results document substantially lower exposures as well as a further decrease temporally associated with the issue of a stricter dietary advisory.

Adult↗
PubMed2005

Effects of breast feeding on neuropsychological development in a community with methylmercury exposure from seafood.

Breastfeeding has been associated with an advantage to infant neurobehavioral development, possibly in part due to essential nutrients in breast milk. However, breast milk may be contaminated by environmental neurotoxicants, such as methylmercury. In the Faroe Islands, where maternal consumption of pilot whale may cause transfer of marine toxicants into breast milk, a cohort of 1022 consecutive singleton births was generated during 1986-87. Methylmercury exposure was assessed from mercury concentrations in cord blood and in the hair of the child at age 12 months, and the duration of breastfeeding was recorded. At approximately 7 years of age, 917 (90%) of the children underwent detailed neurobehavioral examination. After adjustment for confounders, breastfeeding was associated with only marginally better neuropsychological performance on most tests. These associations were robust even after adjustment for cord-blood and hair mercury concentration at age 1 year. Thus, in this cohort of children with a relatively high prenatal toxicant exposure and potential exposure to neurotoxicants through breast milk, breastfeeding was associated with less benefits on neurobehavioral development than previously published studies though not associated with a deficit in neuropsychological performance at age 7. Although the advantage may be less, Faroese women can still safely breastfeed their children.

Adult↗
PubMed2005

Umbilical cord mercury concentration as biomarker of prenatal exposure to methylmercury.

Biomarkers are often applied to assess prenatal exposure to methylmercury in research and surveillance. In a prospective study in the Faroe Islands, the main exposure biomarkers were the mercury concentrations in cord blood and maternal hair obtained at parturition. We have now supplemented these exposure biomarkers with mercury analyses of umbilical cord tissue from 447 births. In particular, when expressed in relation to the dry weight of the tissue, the cord mercury concentration correlated very well with that in cord blood. Structural equation model analysis showed that these two biomarkers have average total imprecision of about 30%, which is much higher than the laboratory error. The imprecision of the dry-weight-based concentration was lower than that of the wet-weight-based parameter, and it was intermediate between those of the cord blood and the hair biomarkers. In agreement with this finding, regression analyses showed that the dry-weight cord mercury concentration was almost as good a predictor of methylmercury-associated neuropsychologic deficits at 7 years of age as was the cord-blood mercury concentration. Cord mercury analysis can therefore be used as a valid measure of prenatal methylmercury exposure, but appropriate adjustment for the imprecision should be considered.

Atlantic Islands↗
PubMed2004

Criteria for skin notation in different countries.

BACKGROUND: Skin notation criteria was introduced almost 50 years ago as a qualitative indicator of a hazard related to dermal absorption at work. However, risk is not a qualitative term, but needs a quantitative measure to be useful for prevention. For this reason, some countries have developed alternative criteria for assigning skin notations to industrial chemicals. METHODS: The present analysis compares the current use of skin notations on lists of exposure limits for industrial chemicals in six countries. RESULTS: Up to one-third of industrial chemicals listed now have a skin notation. The criteria for assigning skin notation differ but cannot explain the substantial discrepancies between countries that otherwise have very comparable occupational exposure limits (OELs). CONCLUSIONS: The increasing number of chemicals with a skin notation requires a new approach to differentiating between degrees of risk. The first step will be to address the problems related to criteria for assigning skin notations, and the effect of penetration enhancers and mixtures.

Allergens↗
PubMed2004

Implications of the Precautionary Principle in research and policy-making.

The Precautionary Principle (PP) has recently been formally introduced into national and international law. The key element is the justification for acting in the face of uncertainty. The PP is thereby a tool for avoiding possible future harm associated with suspected, but not conclusive, environmental risks. Under the PP, the burden of proof is shifted from demonstrating the presence of risk to demonstrating the absence of risk and it is the responsibility of the producer of a technology to demonstrate its safety rather than the responsibility of public authorities to show harm. Past experiences show the costly consequences of disregarding early warnings about environmental hazards. Today, the need for applying the PP is even greater. New research is needed to expand current insight into disease causation, to elucidate the full scope of potential adverse implications resulting from environmental pollutants, and to identify opportunities for prevention. Research approaches should be developed and strengthened to counteract innate ideological biases and to support our confidence in applying the PP for decision-making in the public policy arena.

Environmental Exposure↗
PubMed2004

Association between mercury concentrations in blood and hair in methylmercury-exposed subjects at different ages.

Mercury concentrations were measured in paired hair and blood samples from a cohort of about 1000 children examined at birth and at 7 and 14 years of age. The ratio between concentrations in maternal hair (in microg/g) and in cord blood (microg/L) was approximately 200, but samples from the children at age 14 years showed a ratio of about 250. These findings are in accordance with previous data from smaller studies. However, an even higher ratio of about 360 was seen at 7 years of age, suggesting that hair strands at this age retain more mercury. The 95th percentile of the hair-to-blood ratio was between five-fold and nine-fold greater than the 5th percentile. The results were examined in structural equation models to estimate the total imprecision of the individual biomarker results and the possibility that the ratio may not be constant. The hair-to-blood ratio was found to increase at lower mercury concentrations, a tendency that could not be explained by potential confounders, such as alcohol intake or number of amalgam fillings. The total imprecision (coefficient of variation) for the blood determinations averaged about 30%, thereby substantially exceeding normal laboratory imprecision. Yet hair-mercury results had an even greater imprecision, which suggested that preanalytical factors, such as variable sample characteristics, impacted the results. These findings are in accordance with other evidence that the cord blood concentration is a better predictor of neurobehavioral toxicity than is the maternal hair concentration. Although practical for field studies and monitoring purposes, hair-mercury concentration results, therefore, need to be calibrated and interpreted in regard to each specific study setting.

Adolescent↗
PubMed2004

Cardiac autonomic activity in methylmercury neurotoxicity: 14-year follow-up of a Faroese birth cohort.

OBJECTIVE: To determine whether heart function in childhood is affected by exposure to methylmercury (MeHg) from seafood. STUDY DESIGN: Prospective study of a Faroese birth cohort (N=1022). Examinations at ages 7 and 14 years included blood pressure, heart rate variability (HRV) and its frequency components of autonomic origin, and brainstem auditory evoked potentials (BAEPs). Mercury concentrations were determined in cord blood and in the child's hair. RESULTS: Both low-frequency (LF) and high-frequency (HF) activities decreased by about 25% from 7 to 14 years; they correlated well with the blood pressures. A doubling of prenatal MeHg exposure was associated with a decrease in LF and HF powers of about 6.7% (P=.04) and in the coefficient of variation of the electrocardiographic R-R interval of 2.7% (P=.04) at age 14 years. No discernible effect on blood pressure was apparent. Decreased LF variability was associated with increased latency of BAEP peak III, but adjustment for MeHg exposure substantially attenuated this correlation. CONCLUSIONS: Methylmercury exposure was associated with decreased sympathetic (LF) and parasympathetic (HF) modulation of the HRV. Parallel MeHg-related delays of BAEP latencies may be caused by underlying MeHg neurotoxicity to brainstem nuclei.

Adolescent↗
PubMed2004

Delayed brainstem auditory evoked potential latencies in 14-year-old children exposed to methylmercury.

OBJECTIVE: To determine possible exposure-associated delays in auditory brainstem evoked potential latencies as an objective measure of neurobehavioral toxicity in 14-year-old children with developmental exposure to methylmercury (MeHg) from seafood. STUDY DESIGN: Prospective study of a birth cohort in the Faroe Islands, where 878 of eligible children (87%) were examined at age 14 years. Latencies of brainstem evoked potential peaks I, III, and V at 20 and 40 Hz constituted the outcome variables. Mercury concentrations were determined in cord blood and maternal hair, and in the child's hair at ages 7 and 14. RESULTS: Latencies of peaks III and V increased by about 0.012 ms when the cord blood mercury concentration doubled. As seen at age 7 years, this effect appeared mainly within the I-III interpeak interval. Despite lower postnatal exposures, the child's hair mercury level at age 14 years was associated with prolonged III-V interpeak latencies. All benchmark dose results were similar to those obtained for dose-response relationships at age 7 years. CONCLUSIONS: The persistence of prolonged I-III interpeak intervals indicates that some neurotoxic effects from intrauterine MeHg exposure are irreversible. A change in vulnerability to MeHg toxicity is suggested by the apparent sensitivity of the peak III-V component to recent MeHg exposure.

Adolescent↗
PubMed2004

Effects of exposure imprecision on estimation of the benchmark dose.

In regression analysis failure to adjust for imprecision in the exposure variable is likely to lead to underestimation of the exposure effect. However, the consequences of exposure error for determination of safe doses of toxic substances have so far not received much attention. The benchmark approach is one of the most widely used methods for development of exposure limits. An important advantage of this approach is that it can be applied to observational data. However, in this type of data, exposure markers are seldom measured without error. It is shown that, if the exposure error is ignored, then the benchmark approach produces results that are biased toward higher and less protective levels. It is therefore important to take exposure measurement error into account when calculating benchmark doses. Methods that allow this adjustment are described and illustrated in data from an epidemiological study on the health effects of prenatal mercury exposure.

Algorithms↗
PubMed2004

Implications of the precautionary principle for primary prevention and research.

The precautionary principle (PP) is an extension of the public health presage that prevention is better than cure. The PP has recently achieved new relevance in regard to serious but uncertain threats to human health and the environment and has now entered national and international legislation. However, frameworks for its unambiguous application in practice are yet to be designed. They will depend on legal and cultural circumstances and are likely to involve pluralities of perspectives and stakeholder participation. The rules for causal reasoning and dose dependence need to be addressed and may be conveniently expressed in accordance with probability theory. Although the PP will allow action before convincing evidence is secured, it is not science averse. However, it provides an occasion to review environmental health research strategies, methodologies, and research-reporting traditions. From this perspective, current research is afflicted by important biases and insufficient focus on major environmental health problems.

Decision Making↗
PubMed2004

Underestimation of risk due to exposure misclassification.

Exposure misclassification constitutes a major obstacle when developing dose-response relationships for risk assessment. A non-differentional error results in underestimation of the risk. If the degree of misclassification is known, adjustment may be achieved by sensitivity analysis. The purpose of this study was to examine the full magnitude of measurement error in determining the prenatal exposure to methylmercury. We used data from a prospective study of a Faroese birth cohort. Two biomarkers of methylmercury exposure were available, i.e., the mercury concentrations in cord blood and in maternal hair (sampled at the time of parturition). The laboratory imprecision on both chemical analyses was thought to be below 5% coefficient of variation (CV). As a third exposure parameter, we used the dietary questionnaire response on frequency of whale meat dinners. Factor analysis and structural equation analysis were applied to assess the full extent of the imprecision. The calculated total imprecision much exceeded the known laboratory variation: the CV was 28-30% for the cord-blood concentration and 52-55% for the maternal hair concentration. The dietary questionnaire response was even more imprecise. These findings illustrate that measurement error may be greatly underestimated if judged solely from reproducibility or laboratory quality data. Adjustment by sensitivity analysis is meaningful only if realistic measurement errors are applied. When exposure measurement errors are overlooked or underestimated, decisions based on the precautionary principle will not appropriately reflect the degree of precaution that was intended.

Biomarkers↗
PubMed2003

Consequences of exposure measurement error for confounder identification in environmental epidemiology.

Non-differential measurement error in the exposure variable is known to attenuate the dose-response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse health effects of prenatal mercury exposure.

Bias↗