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Huel Guy


guy.huel@inserm.fr

Journal articles

2009
Chadi Yazbeck, Olivier Thiebaugeorges, Thierry Moreau, Valérie Goua, Ginette Debotte, Josiane Sahuquillo, Anne Forhan, Bernard Foliguet, Guillaume Magnin, Rémy Slama, Marie-Aline Charles, Guy Huel (2009)  Maternal blood lead levels and the risk of pregnancy-induced hypertension: the EDEN cohort study.   Environ Health Perspect 117: 10. 1526-1530 Oct  
Abstract: BACKGROUND: Prior studies revealed associations of environmental lead exposure with risks of hypertension and elevated blood pressure. OBJECTIVE: We examined the effect of blood lead levels on blood pressure and the incidence of pregnancy-induced hypertension (PIH) in the second and third trimesters of pregnancy. METHODS: One thousand seventeen pregnant women were enrolled in two French municipalities between 2003 and 2005 for the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l' Enfant) cohort study. Blood lead concentrations were measured by atomic absorption spectrometry in mothers between 24 and 28 weeks of gestation. RESULTS: PIH was diagnosed in 106 subjects (10.9%). Age, parity, weight gain, alcohol, smoking habits, and calcium supplementation were comparable between hypertensive and nonhypertensive women. Lead levels were significantly higher in PIH cases (mean +/- SD, 2.2 +/- 1.4 microg/dL) than in normotensive patients (1.9 +/- 1.2 microg/dL; p = 0.02). Adjustment for potential confounder effects slightly attenuated but did not eliminate the significant association between blood lead levels and the risk of PIH (adjusted odds ratio of PIH = 3.3; 95% confidence interval, 1.1-9.7). We also observed geographic differences in lead exposure and in the incidence of PIH and found significant correlations between blood lead levels and unadjusted as well as adjusted systolic and diastolic blood pressures after 24 weeks of gestation. CONCLUSIONS: These findings confirm the relationship between blood lead levels at mid-pregnancy and blood pressure and suggest that environmental lead exposure may play an etiologic role in PIH.
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Melanie Lemire, Donna Mergler, Guy Huel, Carlos J S Passos, Myriam Fillion, Aline Philibert, Jean R D Guimarães, Isabelle Rheault, Julie Borduas, Gabrielle Normand (2009)  Biomarkers of selenium status in the Amazonian context: blood, urine and sequential hair segments.   J Expo Sci Environ Epidemiol 19: 2. 213-222 Feb  
Abstract: Selenium (Se) is an essential element and deficit or excess of dietary Se is associated with health disorders. Relatively elevated Se levels have been reported in the Brazilian Amazon, where there are also important annual variations in the availability of different foods. The present study was conducted among six riparian communities of the Tapajós River to evaluate seasonal variations in blood and sequential hair cm Se concentrations, and to examine the relationships between Se in blood and hair, and blood and urine. Two cross-sectional studies were conducted, at the descending water (DWS, n=259) and the rising water (RWS, n=137) seasons, with repeated measures for a subgroup (n=112). Blood Se (B-Se), hair Se (H-Se) and urine Se (U-Se) were determined. Match-paired analyses were used for seasonal comparisons and the method of best fit was used to describe the relationships between biomarkers. B-Se levels presented a very large range (142-2447 microg/l) with no overall seasonal variation (median 284 and 292 microg/l, respectively). Sequential analysis of 13 cm hair strands showed significant variations over time: Se concentrations at the DWS were significantly lower compared with the rising water season (medians: 0.7 and 0.9 microg/g; ranges: 0.2-4.3 microg/g and 0.2-5.4 microg/g, respectively). At both seasons, the relationships between B-Se and H-Se were linear and highly significant (r(2)=67.9 and 63.6, respectively), while the relationship between B-Se and U-Se was best described by a sigmoid curve. Gender, age, education and smoking did not influence Se status or biomarker relationships. Variations in H-Se suggest that there may be seasonal availability of Se sources in local food. For populations presenting a large range and/or elevated Se exposure, sequential analyses of H-Se may provide a good reflection of variations in Se status.
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Nadia Abdelouahab, Guy Huel, Alexander Suvorov, Bernard Foliguet, Valérie Goua, Ginette Debotte, Josianne Sahuquillo, Marie-Aline Charles, Larissa Takser (2009)  Monoamine oxidase activity in placenta in relation to manganese, cadmium, lead, and mercury at delivery.   Neurotoxicol Teratol Sep  
Abstract: BACKGROUND: Environmental prenatal exposure to potentially neurotoxic metals poses a particular challenge with regard to the study of early toxic effects. Monoamine oxidase activity, shown to be influenced by metals in experimental studies, could be a useful biomarker in humans. OBJECTIVE: To examine the relationship between blood metal concentrations at delivery and placenta MAO activity. METHODS: The study was performed in 163 pregnancies. Maternal and cord blood samples were obtained for manganese (Mn), lead (Pb), and cadmium (Cd) determination. Mercury (Hg) was also analysed in maternal hair. Placental samples were stored immediately after expulsion and total MAO activity was measured. RESULTS: MAO activity was significantly positively correlated with maternal and cord blood Mn concentrations in subjects with high MAO activity. In subjects with low MAO activity, maternal hair Hg was negatively correlated with MAO. CONCLUSION: Our results suggest the use of placental MAO as a potential surrogate marker of Mn toxicity in the newborn and its correlation with psychomotor development should be further investigated.
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2008
Guy Huel, Josiane Sahuquillo, Ginette Debotte, Jean-François Oury, Larissa Takser (2008)  Hair mercury negatively correlates with calcium pump activity in human term newborns and their mothers at delivery.   Environ Health Perspect 116: 2. 263-267 Feb  
Abstract: BACKGROUND: Calcium homeostasis is a known target of several environmental toxicants including lead and mercury. OBJECTIVE: Our goal was to determine the relationship between Hg exposure and erythrocyte Ca pump activity in women at delivery and in their newborns. METHODS: We determined total Hg as well as Pb concentrations in 81 hair and blood samples obtained at delivery. Basal and calmodulin-stimulated Ca pump activity was measured in red blood cells from cord blood and maternal erythrocyte plasma membranes. RESULTS: Maternal hair Hg negatively correlates with Ca pump activity in maternal and cord blood erythrocytes. Pb and Hg both independently correlate negatively with Ca pump activity without any statistically significant interaction. After adjustment for potential confounders, Pb and Hg explain about 30% and 7% of total variance of Ca pump activity in newborns and mothers, respectively. CONCLUSION: Our findings confirm results reported in previous experimental studies and support the use of biomarkers in newborns from general population.
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2006
Chadi Yazbeck, Thierry Moreau, Josiane Sahuquillo, Larissa Takser, Guy Huel (2006)  Effect of maternal manganese blood levels on erythrocyte calcium-pump activity in newborns.   Sci Total Environ 354: 1. 28-34 Jan  
Abstract: Manganese (Mn) is widely distributed in the biosphere but occurs in only trace amounts in animal tissues. Although Mn deficiency and toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. In vitro studies suggest that transport proteins are affected by Mn, lead (Pb), and selenium (Se). Among these transport proteins, the calmodulin-regulated calcium pump (Ca(2+)Mg(2+)ATPase) could be inhibited by Mn. In order to understand Mn biochemical pathways, we examined the relationships between Mn blood levels and red blood cell Ca-pump activity among 248 mothers and newborns, environmentally exposed to Mn, Pb, and Se. POPULATION AND METHODS: 248 mother-newborn pairs were recruited at Robert Debré University Hospital (Paris). Blood Mn and Pb concentrations were measured by absorption spectrophotometry. Se was measured by fluorometric method. Red blood cell membrane suspensions were obtained for Ca-pump activity measurements. Linear and quadratic regression models and Pearson correlation were performed. RESULTS: A non-linear parabolic relationship between maternal Mn blood levels and newborn Ca-pump activity was discovered from the analysis of the observed data. The peak level of maternal Mn that corresponded to a maximal activity of the newborn Ca-pump was estimated at 23.9 microg/l with a 95% confidence interval of 17.6 to 32.4 microg/l. An inhibition of this enzyme was observed at low and high levels of maternal Mn. The relationships between the newborn Ca-pump activity and maternal Se and Pb levels became non-significant after adjustment on all the co-factors included in the final model. CONCLUSION: Maternal environmental exposure to Mn, as reflected by maternal blood levels of this metal, is associated with a reduced activity of newborn erythrocyte Ca-pump in a non-linear pattern. Mn levels between 17.6 and 32.4 microg/l in maternal blood probably correspond to the optimal physiological concentration for the metabolism of this enzyme in newborns.
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2005
Chadi Yazbeck, Wolfram Kloppmann, Roger Cottier, Josiane Sahuquillo, Ginette Debotte, Guy Huel (2005)  Health impact evaluation of boron in drinking water: a geographical risk assessment in Northern France.   Environ Geochem Health 27: 5-6. 419-427 Sep  
Abstract: OBJECTIVE: To evaluate health impact of boron in drinking water. METHODS: A regional scale geographical study in Northern France was conducted. Assessment of boron blood levels in a group of 180 healthy individuals and correlation with boron content in drinking water were followed by an assessment of health indicators such as birth rates, mortality rates, and sex ratios in zones of different boron content in drinking water. RESULTS: After necessary adjustments, men living in municipalities with more than 0.30 mg/L of boron in drinking water had elevated but not significant boron blood levels compared with those living in municipalities with boron water levels of less than 0.30 mg/L (159.1 versus 123.0 ng/g; p > 0.05). The standardized birth ratio adjusted for the reference geographic zone and calendar time period was 1.07 and 1.28 in the low and high (>0.3 mg/L) boron content municipalities, respectively. The birth rate in municipalities with high boron content in drinking water was higher than that of the reference geographic zone and of the French general population (p < 10(-4)). The standardized mortality ratio adjusted for the reference geographic zone and calendar time period was 0.94 and 0.92 in the low and high boron content municipalities, respectively. The mortality rate in municipalities with high boron content in drinking water was less than that of the reference geographic zone and of the French general population (p < 10(-3)). No statistical difference was noted in the male-female sex ratios between the different municipality zones (p = 0.45). CONCLUSIONS: The results of this study do not support the idea of a deleterious effect of boron on human health, at the boron water level contents found in this specific region. In fact, there is a tendency toward a beneficial effect with low-dose environmental exposure (less than 1 mg/L of boron) in drinking water.
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2004
Guy Huel, Chadi Yazbeck, Daniel Burnel, Pascale Missy, Wolfram Kloppmann (2004)  Environmental boron exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in a newborn population.   Toxicol Sci 80: 2. 304-309 Aug  
Abstract: Following boron intake, multiple effects have been observed in animal experiments. However, human data is lacking, and no data is available on the ability of boron to accumulate in fetal tissues. Positive responses in animal species suggest that developmental toxicity may be an area of concern in humans, following exposure to boron. Two hypotheses have seemed to account for the multiple effects described in scientific findings. One hypothesis is that boron is a negative regulator that influences a number of metabolic pathways by competitively inhibiting some key enzyme reactions. The other hypothesis is that boron has a role in ionic membrane transport regulations. To better understand boron potential toxicity, the present study examined the relationship between boron exposure and some key enzymes, well-known for their affinity for mineral elements, such as delta-aminolevulinic acid dehydratase (ALA-D), and two fundamental enzymes having a role in ionic membrane transport regulations (Ca-pump and Na(+)K(+)-ATPase). We investigated the potential effects of an environmental boron exposure on the activity of these enzymes in an urban population of 197 "normal" newborns. Environmental boron exposure was assessed in placental tissue. Because of the well-known inhibiting effect of lead on these enzymes, cord blood and placental lead were also analyzed. After adjustment for potential confounders, including lead, placental boron levels were negatively significantly correlated to ALA-D activity while Ca-pump and Na(+)K(+)-ATPase activities did not seem to be affected by the level of boron exposure. Given boron's ability, as a Lewis acid, to complex with hydroxyl groups, we suggest that such a mechanism would explain the inhibiting effect of boron on ALA-D.
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2003
G Huel, L Takser, J Sahuquillo, F Girard, G Hellier, P Blot (2003)  Biological materials collection within population of pregnant women at delivery   Rev Epidemiol Sante Publique 51: 1 Pt 2. 167-174 Feb  
Abstract: Little is known about biochemical mechanisms associated with the normal psychomotor development of children. Many factors of the fetal environment likely interfere with these mechanisms. A prospective cohort study is essential to explain the implications of certain disturbances of biochemical nature during gestation on the later development of the nervous system. The study that we undertook with the maternity hospital Robert Debré had several objectives. The first was to examine, on an epidemiological scale, the possible role of the monoaminergic systems and the ATPases activity during the perinatal period on the later cognitive development of the child. The second was to study the influence of environmental in utero exposure on these mechanisms and consequently on the later psychomotor performances of the child. We examine here the advantages and the specific difficulties in such an approach within a population of women in childbirth.
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Larissa Takser, Donna Mergler, Georgette Hellier, Josiane Sahuquillo, Guy Huel (2003)  Manganese, monoamine metabolite levels at birth, and child psychomotor development.   Neurotoxicology 24: 4-5. 667-674 Aug  
Abstract: Several studies have demonstrated neurobehavioral impairment related to manganese (Mn) exposure in the workplace. Exposure to high doses of manganese is associated with irreversible neurodegenerative disorders resembling idiopathic Parkinson disease. Although there is a risk of Mn accumulation in the foetus during pregnancy, little information exists about developmental effects of environmental low-level exposure in human. For this reason, we conducted a prospective epidemiological study in 247 healthy pregnant women and their babies to determine the long-term effect of in utero Mn levels on child's psychomotor development. Concurrently, we examined the relationship between Mn tissue levels at delivery and foetal plasma monoamine metabolites. Of the newborns, 195 were examined at 9 months, 126 at 3 years and 100 at 6 years. At 9 months, the Brunet-Lézine scales were administered. The McCarthy scales of children's abilities were used at 3 and 6 years. After adjustment for potential confounding co-factors (child's gender, mother's educational level), negative relationships were observed between cord blood Mn levels and several psychomotor sub-scales at age of 3 years: "attention" (partial r=-0.33, P<0.001), "non-verbal memory" (partial r=-0.28, P<0.01), and "hand skills" (partial r=-0.22, P<0.05). No significant relationships were observed between Mn measures at birth and the general psychomotor indices, Brunet-Lézine developmental quotient (DQ) at 9 months or McCarthy general cognitive index (GCI) at 3 and 6 years. Maternal blood Mn levels were negatively associated with foetal plasma HVA and 5-HIAA concentrations (adjusted for labour duration, child's gender, and smoking during pregnancy), but the adjustment for monoamine levels at birth did not change the association between the Mn levels and the psychomotor scores. These results suggest that environmental Mn exposure in utero could affect early psychomotor development.
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I Annesi-Maesano, R Pollitt, G King, J Bousquet, G Hellier, J Sahuquillo, G Huel (2003)  In utero exposure to lead and cord blood total IgE. Is there a connection?   Allergy 58: 7. 589-594 Jul  
Abstract: BACKGROUND: Lead exposure and total immunoglobulin E (IgE) have been shown to be positively related in animals and humans even at lead levels below those recognized as toxic. In the last decades, exposure to lead has become more frequent in urban areas of industrialized as well as of developing countries where IgE-mediated allergy prevalence has also increased. METHODS: We examined for the first time the relationship between in utero exposure to lead and cord blood total IgE in two samples of 137 and 237 mother-newborn pairs, respectively, recruited in Paris. RESULTS: Cord blood IgE was positively related to hair lead level at birth, providing an integrated measure of long-term exposure in utero, in each cohort (Spearman's coefficient r = 0.32, P < 0.001 and r = 0.19, P < 0.01, respectively) and in the combined cohort (r = 0.21; P < 0.01). The relationship appeared to be more pronounced in newborns of nonallergic mothers (r = 0.24; P < 0.01) than in those of allergic mothers (r = 0.12). This could be due to the fact that familial history of allergy, the strongest determinant of IgE development, may overshadow the influence of lead on IgE in the offspring. CONCLUSIONS: Our findings suggest a possible intervention of environmental exposure besides genetic factors in early life development of IgE production. Further studies are needed to confirm the finding.
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Larissa Takser, Dave Campagna, Phillippe Blot, Guy Huel (2003)  Could monoamine plasma levels and erythrocyte membrane ATPase activities at birth be predictive for future hand performance?   Pediatr Res 54: 3. 358-363 Sep  
Abstract: The monoamine and intracellular calcium systems are two major elements of nervous system functions. However, their role in human brain development is unclear. We studied the association between activity of monoamine and intracellular calcium systems during prenatal life and subsequent psychomotor performances in healthy children. We used prospective data from 247 children followed from birth through 6 y of age. Among those, 195 were examined at 9 mo using the Brunet-Lézine Scales, whereas 126 were examined at 3 y and 100 at 6 y using the McCarthy Scales of Children's Ability. A blood sample was collected from the umbilical cord to measure levels of dopamine and serotonin metabolites (homovanillic acid and 5-hydroxyindoleacetic acid, respectively) and ATPase activities (Na+K+-ATPase and Ca2+Mg2+-ATPase). The hand skill score at 6 y of age was significantly and negatively correlated with ATPase activities and with monoamine metabolite concentrations. No other cognitive score was related to biochemical measures at birth. Results were adjusted for child's sex, mother's educational level, duration of labor, and tea consumption. Composite scores of ATPase activities and monoamine metabolite concentrations measured at birth explained 29% of hand skill score variance at 6 y. Our results demonstrate the importance of prenatal factors on monoaminergic and ATPase activities in early human psychomotor development. This study also suggests that specific psychometric measures such as fine motor tests may be a better developmental measurement to correlate with biochemical factors than general cognitive scales.
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2002
Audrey Smargiassi, Larissa Takser, André Masse, Martin Sergerie, Donna Mergler, Geneviève St-Amour, Philippe Blot, Georgette Hellier, Guy Huel (2002)  A comparative study of manganese and lead levels in human umbilical cords and maternal blood from two urban centers exposed to different gasoline additives.   Sci Total Environ 290: 1-3. 157-164 May  
Abstract: Manganese (Mn) and lead (Pb) are two neurotoxic chemicals and experimental evidence suggests that they can cross the placental barrier. Tetraethyl lead was still in use as an antiknock agent in Paris during the sampling period of the study, while it has been replaced by methylcyclopentadienyl manganese tricarbonyl (MMT) in Canada since 1977. By 1990, MMT was in 100% of gasoline in Canada. In a study of 160 pairs of mothers-neonates in Montreal and 206 pairs in Paris, we compared levels of Mn and Pb in the umbilical cord and in maternal blood. Neonates and mothers had significantly higher Pb levels in Paris where lead additives were still used in gasoline. Geometric mean maternal blood Pb levels were 5.4 microg/dl compared to 2.1 microg/dl in Montreal and cord blood Pb levels were 3.2 microg/dl in Parisian mothers compared to 1.7 microg/dl in Montreal. The prevalence of Paris Pb values superior to the 95th percentile of the Montreal distribution was highly elevated in all media studied. The prevalence of high Mn levels in umbilical cord blood was also significantly higher in Montreal. Surveillance programs are important to limit Pb overexposure and associated neurological effects in neonates where tetraethyl Pb is still in use as a gasoline additive. Since Mn is an essential element and dietary Mn intake may differ between Montreal and Paris, the difference observed with regard to high Mn values between Montreal and Paris cannot, at this time, be attributed to MMT in Montreal's gasoline. Further studies are needed to infer an association between Mn emissions from MMT and prenatal exposure to Mn.
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G Huel, N Fréry, L Takser, M Jouan, G Hellier, J Sahuquillo, J P Giordanella (2002)  Evolution of blood lead levels in urban French population (1979-1995).   Rev Epidemiol Sante Publique 50: 3. 287-295 Jun  
Abstract: BACKGROUND: The aim of the Council Directive of 29 March 1977 of the European Union was to measure non-occupational lead exposure levels in the general adult populations of European countries through biological monitoring. In France, such measurements were carried out during 1979 and 1982 in eight metropolitan areas (having more than 500 000 inhabitants), a period during which the lead content of petrol was decreased. The aim of this study conduct in 1995 was to evaluate the exposure trend to lead. METHODS: In 1995 this measurement was repeated, only in the three largest urban areas (Paris, Marseilles and Lyons). The same sampling method used in the first two campaigns was retained to ensure that the results of 1995 could be compared with those from 1979 and 1982. RESULTS: In these three metropolitan areas, the average blood lead levels decreased by the order of 60 microg/l between the beginning of the 1980's and 1995. This represents a fall of more than 50%. CONCLUSIONS: Certainly car pollution is not the only vector of dissemination of lead in the centre of urban zones, but it is there that the most sustained efforts at eradication have been made. The improvement we have observed is probably due to the policy of eliminating lead from petrol. In conclusion, the blood lead levels in French urban populations seem to have greatly decreased from those of the early 1980s.
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Larissa Takser, Georges Dellatolas, Rosemarie Bowler, Nathalie Laplante, Guy Huel (2002)  Predictive factors of manual dexterity and cognitive performance at 17 years: a 10-year longitudinal study in a rural area of France.   Percept Mot Skills 95: 1. 15-26 Aug  
Abstract: Studies of predictive factors of manual dexterity in adolescents and young adults are lacking. The present longitudinal study reports the relationship between cognitive and behavioural assessments at age 7 years and the schooling, cognitive performance, and manual dexterity at age 17 years. The participants were 65 schoolchildren, 30 boys and 35 girls, from a rural area in France. Assessment at age 7 years included the McCarthy scales and questionnaires measuring the behavior of the child, completed by the mother, the teacher, and the assessing psychologist. Assessment at age 17 years included schooling situation (whether they were in high school or not), cognitive testing (WAIS-R, Trail Making, Verbal Fluency, Cancel H, Stroop, Memory Assessment Scales), and manual dexterity testing (dynamometer, Finger Tapping, Santa Ana Test, Purdue Pegboard). After controlling for effects of parental education and IQ, a negative teachers' rating of children's behaviour and abilities in first-grade (7 years) was correlated with early cessation of schooling, but also, unexpectedly, with higher scores for manual dexterity at 17 years. Manual dexterity was not related to cognitive performance at 17 years. It is suggested that the relationship between manual and cognitive performance varies during development. Although manual exploratory behaviour is an important correlate of early cognitive development, manual dexterity is probably not related to later academic performance.
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2001
D Campagna, B Stengel, D Mergler, J C Limasset, F Diebold, D Michard, G Huel (2001)  Color vision and occupational toluene exposure.   Neurotoxicol Teratol 23: 5. 473-480 Sep/Oct  
Abstract: We examined the relationship between acquired color vision loss and exposure to toluene and total hydrocarbons among 125 male workers. Seventy-two toluene-exposed printers were compared with 34 workers from the same photogravure plant with ambient background exposure, and with 19 workers from a bookbinding plant located in the same town (nonexposed). Environmental mean toluene exposure level at workstation was estimated from individual 8-h sampling. Historic exposure data from the last 30 years were used to construct two cumulative exposure indices, one for toluene and one for total hydrocarbons. Airborne toluene levels were overall lower than the current Threshold Limit Value (TLV) of 50 ppm. Color vision was assessed by the Lanthony D-15 desaturated panel. Color vision loss was quantitatively established by the Color Confusion Index (CCI) and classified by type of acquired dyschromatopsia according to Verriest's classification. CCI was positively related to current airborne toluene levels, and cumulative exposure indices for toluene and total hydrocarbons (.18< or =r< or =.35). Odds ratios of acquired dyschromatopsia were significant for current airborne toluene, toluene, and total hydrocarbon past exposure (1.27 [1.02-1.58], 1.21 [1.04-1.39], 1.15 [1.02-1.31], respectively). In conclusion, this study suggests that the Lanthony D-15 desaturated panel detects early neurotoxic effects among workers exposed to toluene.
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2000
D Campagna, G Huel, G Hellier, F Girard, J Sahuquillo, A Fagot-Campagna, J Godin, P Blot (2000)  Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns.   Life Sci 68: 2. 203-215 Dec  
Abstract: Lead poisoning induces hematological, gastrointestinal and neurological dysfunctions. One of the potential mechanisms is the inhibition of calcium-pump (Ca-pump), a transport protein. We investigated the effects of an environmental low lead exposure on Ca-pump activity in 247 mothers and their newborns. Maternal and cord blood, and newborn and mother hair, were sampled at delivery. Geometric means for mother and cord blood lead (Pb-B), and for mother and newborn hair lead (Pb-H), were 6.3 and 4.8 microg/dl, and 1.7 and 1.1 microg/g. Means for mother and cord basal Ca-pump activities were 2,442 and 2,675 nM/mg/hr. Mother enzymatic activity was negatively related to her Pb-B and Pb-H and to the cord Pb-B and newborn Pb-H levels. Newborn enzymatic activity was negatively related to his Pb-H level only. Adjustment for gestational age, child's sex, mother's age at delivery, alcohol, coffee and tea consumption, and smoking habits during pregnancy did not modify these relationships. Our findings support the hypothesis that lead toxicity could be in part mediated by a reduction of Ca-pump activity. This effect could be observed at low environmental exposure, in mothers and newborns.
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G Huel, D Campagna, F Girard, T Moreau, P Blot (2000)  Does selenium reduce the risk of threatened preterm delivery associated with placental cytochrome P450-1A1 activity?   Environ Res 84: 3. 228-233 Nov  
Abstract: Selenium (Se), an essential trace element in human nutrition, is thought to have an important role in the prevention of oxygen damage by organic hydroperoxides generated by oxidative metabolism. Epidemiological studies have shown an association between placental cytochrome P450-1A1 (CYP1) activity and threatened preterm delivery (TPD), and other experimental studies have shown alterations in fetal development with CYP1 activity or toxicity. The present study examined the possible protective effect of selenium on the potential toxicity of maternal exposure to polycyclic aromatic hydrocarbons (PAHs) on the normal course of pregnancy. Placental CYP1 activity was used as a risk factor resulting from maternal exposure to PAHs. TPD occurrence was used as a general indicator of troubles in the normal course of pregnancy. A group of TPD patients and a group of controls were selected from 178 pregnant women attending obstetrical care in a maternity hospital. Selenium concentrations in maternal plasma were lower in the TPD group: 63.7 ng/ml (CI 95% confidence bounds = 43.6-82.2) vs 69.2 ng/ml (CI 95% confidence bounds = 49. 3-96.3) (t test, P<0.01). When placental CYP1 was induced, an association between TPD and selenium was found, with an increase of 10 ng/ml for the latter. An adjusted odds ratio of 0.55 (CI 95% confidence bounds = 0.34-0.88; chi(2), P<0.01) was estimated. When placental CYP1 was not activated, the odds ratio was estimated at 0.99 (CI 95% confidence bounds=0.95-1.03; NS). This epidemiologic finding suggests that antioxidant Se status may be a protective factor against the potential toxic effect of PAHs on the normal course of pregnancy. The downward trend that we observed supports the hypothesis that the one-electron pathway metabolism of PAHs may explain a large fraction of TPD and some preterm deliveries.
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1999
M P Oryszczyn, I Annesi-Maesano, D Campagna, J Sahuquillo, G Huel, F Kauffmann (1999)  Head circumference at birth and maternal factors related to cord blood total IgE.   Clin Exp Allergy 29: 3. 334-341 Mar  
Abstract: BACKGROUND: A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE. OBJECTIVES: To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account. METHODS: Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications. RESULTS: In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs >/= 37 cm, respectively, P = 0. 03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0. 38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B). CONCLUSIONS: Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE.
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H W Tang, G Huel, D Campagna, G Hellier, C Boissinot, P Blot (1999)  Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters.   J Appl Toxicol 19: 3. 167-172 May/Jun  
Abstract: The objective of this work is to investigate the neurotoxicty of low-level lead exposure in utero on infants and the possible involvement of dopaminergic and serotonergic neurotransmitters. The correlation analysis for cord blood lead level, the concentrations of dopamine metabolite homovanillic acid (HVA) and serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cord plasma and the neurodevelopmental scales of infants were conducted on 244 9-month-old children. Both score of sociability subscale and 5-HIAA concentration were correlated with cord blood lead level. The sociability score was negatively correlated with the concentration of HVA, whereas both the coordination score and the global score were negatively correlated with the concentration of 5-HIAA. With partial correlation analysis, after taking HVA into account, the significant negative correlation between the sociability score and the cord blood lead level that existed in the linear correlation analysis disappeared, and the score of global scale correlated negatively with lead level in cord blood. When taking 5-HIAA into account, the scores of all the neurodevelopmental subscales except the language subscale were significantly negatively correlated with lead level in cord blood. The results indicated that low-level lead exposure in utero could produce a neurotoxic effect on the developing serotonergic system in infants. The neurotoxicity of low-level lead exposure in utero may affect the sociability of infants. Serotonergic activity was shown to have a potential effect on neurodevelopmental assessment. It may interfere with the association between low-level lead exposure in utero and other neurodevelopmental performances of 9-month-old children.
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D Campagna, G Huel, F Girard, J Sahuquillo, P Blot (1999)  Environmental lead exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in maternal and cord blood.   Toxicology 134: 2-3. 143-152 Jun  
Abstract: The hypothesis that environmental lead exposure measured from blood (Pb-B) inhibits delta-aminolevulinic acid dehydratase activity (ALA-D) from whole blood was tested in 241 urban mothers and their newborns. Geometric means and (5th and 95th Percentiles) for maternal and cord Pb-B were 6.4 microg dl(-1) (3.4-11.9) and 4.6 microg dl(-1) (2.8-9.2). Spearman correlations between mother and cord Pb-B and ALA-D were all negative but statistically significant only for cord Pb-B and mother ALA-D. A potential lead threshold, was identified between 3.2 and 4.8 microg dl(-1), above which ALA-D may be inhibited by lead, and below which ALA-D may be insensitive or even activated. In conclusion, low environmental exposure to lead is responsible for a demonstrable biochemical effect. This potential ALA-D inhibition may lead to neurotoxic effects, especially in newborns who have high level of neurogenesis.
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1997
R M Bowler, L Ngo, C Hartney, K Lloyd, I Tager, J Midtling, G Huel (1997)  Epidemiological health study of a town exposed to chemicals.   Environ Res 72: 2. 93-108 Feb  
Abstract: The purpose of this survey was to assess the health status of community residents exposed to a 16-day release of Catacarb from a nearby refinery and to document the prevalence rates of symptoms and illnesses of this town. The health status of the exposed residents was compared to that of unexposed residents of a demographically similar control town. An epidemiologic study design was used and questionnaires were mailed to all households in both towns. Response rate was 43%. Household cluster effects, gender, education, and race were controlled in the analysis. Questionnaire health data reveal increased reporting of symptoms in the exposed, specifically headaches, respiratory, visual, gastrointestinal, and dermatologic with odds ratios ranging between 1.3 and 3. Exposure relationships with increased symptoms and worsening of illnesses was found.
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1996
D Campagna, F Gobba, D Mergler, T Moreau, C Galassi, A Cavalleri, G Huel (1996)  Color vision loss among styrene-exposed workers neurotoxicological threshold assessment.   Neurotoxicology 17: 2. 367-373  
Abstract: Styrene represents nowadays one of the most used organic solvent. The current exposure limit proposed for this chemical differs significantly from country to country: the Threshold Limit Value-Time Weighted Average (TLV-TWA) proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) is 50 ppm while the German, Finnish and Swedish occupational exposure limit is 20 ppm. Nevertheless, effects on the nervous system were recently reported in workers exposed at TWA styrene levels below the current TLV. Neuro-optic pathways have been shown to be particularly vulnerable to organic solvent exposure. Analysis and measurements of visual functions can provide important information on early neurotoxic effects. Previous studies support the hypothesis that styrene exposure can induce a dose-dependent color vision loss. The aim of this study is to assess a threshold level below which no detectable effect occurs for color vision. We applied a sub-application of the change point problem in two-phase regression considering one phase as a constant line. In accordance with this model the maximum-likelihood technique was used as a method to examine the dose- effect relationship between external styrene exposure and chromatic discrimination. The present article presents a joint analysis of data from two previously published studies, one carried out in Canada and the other in Italy. The age and seniority of the workers from both countries were remarkably similar, as were the process type, the chemicals used and the work-tasks of exposed subjects. The mathematical method presented here shows the existence of a statistically significant threshold. This finding shows that, in fiberglass-reinforced plastics industry, visual color impairment could be significantly detected above 4 ppm (upper limit of the confidence interval at 5% = 26 ppm). The exact clinical meaning of this effect, and also the progress of the impairment in exposed workers, is still to be assessed in further studies. The results of our study support the need of a reduction of the occupational limits for styrene in workplaces to values close to or lower than German, Finnish or Swedish exposure limits.
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D Mergler, G Huel, S Bélanger, R M Bowler, G Truchon, D Drolet, C Ostiguy (1996)  Surveillance of early neurotoxic dysfunction.   Neurotoxicology 17: 3-4. 803-812 Fall/Winter  
Abstract: Surveillance of early neurotoxic alterations was undertaken in 3 reinforced plastics plants, with a view to preventive intervention. Using a longitudinal study design, exposure parameters (environmental styrene in the respiratory zone of each worker and end-shift mandelic acid (MA)) and neurobehavioral performance (Neurobehavioral Core Test Battery and Field Assessment: Sensory Tests), were assessed at time zero (T0); recommendations were made to reduce exposure at jobsites with the highest risk. Reassessment was made two years later (T2). Complete exposure data was available for 118 workers at T0; 75 were still employed at T2; of these, 57 (76%) returned for testing. Those who returned had more seniority (p < 0.001) and higher MA (p < 0.01) and styrene (p < 0.05) levels at T0 than the others. Analyses, performed on the T0-T2 differences, showed improvement in exposure parameters in Plant 3, where lower levels were observed at T2 for styrene (p < 0.05) and MA (p < 0.001). workers in Plant 3 (n = 29) performed better (p < 0.05) at T2 for short term memory, perceptuo-motor speed, motor precision and manual dexterity; they reported more vigor (p < 0.05) and less anger (p = 0.07). This was not the case for the workers from the other plants. Generally, the T0-T2 difference in MA was associated (Spearman's Rho) with differences in color vision (p < 0.001), simple reaction time (mean and standard deviation), digit span forward, tension, fatigue and the number of symptoms (p < 0.05); aiming precision showed a similar tendency (p < 0.10). These findings suggest that group surveillance of early nervous system changes for jobs with exposure to neurotoxins, using a sensitive neurofunctional test battery, may be useful for preventive intervention.
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R M Bowler, G Huel, D Mergler, J E Cone, S S Rauch, C Hartney (1996)  Symptom base rates after chemical exposure for white, Hispanic and African-Americans.   Neurotoxicology 17: 3-4. 793-802 Fall/Winter  
Abstract: The results of a symptom checklist of three matched-pair studies (N = 460) of the following exposed groups are presented: Study 1, a primarily white community (N = 220) environmentally exposed to the pesticide metam sodium; Study 2, a Hispanic group (N = 180) who worked in a microelectronics plant and had extensive past exposure (M = 6.7 yrs) to multiple organic hydrocarbon solvents; and Study 3, an African-American group (N = 168) environmentally exposed to sulfuric acid. Each exposed group was compared to a matched (race, age +/- 3 years, gender, education +/- 2 years and number of children) unexposed reference group, resulting in 90 pairs for the white metam sodium group, 62 pairs for the Hispanic organic solvent group, and 78 pairs for the African-American sulfuric acid group. Symptom prevalence rates and relative risk ratios show very strong associations: in Study 1, the relative risk for all 33 symptoms ranged from 1.5 to 37; in Study 2, the relative risk for 31 of the symptoms ranged from 1.5 to 11.1; and in Study 3, the relative risk for 16 of the symptoms ranged from 1.5 to 6. Mann Whitney U results of each symptom indicate significantly greater symptomatology in the exposed vs. the reference groups in all three studies: in Study 1, at p < .01 for all 33 symptoms; in Study 2, at p < .01 for 31 symptoms, and p < .05 for one additional symptom; and in Study 3, at p < .01 for 24 symptoms and p < .05 for another three symptoms. These results suggest a robust symptom complex following chemical exposure regardless of specific chemical.
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1995
A M Lee, G Huel, J Godin, G Hellier, J Sahuquillo, T Moreau, P Blot (1995)  Inter-individual variation of selenium in maternal plasma, cord plasma and placenta.   Sci Total Environ 159: 2-3. 119-127 Jan  
Abstract: Selenium (Se) in high doses has been known to cause injury to the fetus and newborn. The major difficulty in assessing the effects of selenium on human reproduction stems from the need for a suitable means of estimating maternal and fetal exposure. The present investigation, therefore, examines the respective reliability of maternal plasma, cord plasma and placenta as epidemiological indicators as well as inter-individual variation of this trace element. An unselected population of 128 pregnancies was studied. Obstetrical characteristics were noted. Selenium concentrations were determined for maternal plasma, cord plasma, and placental tissue by fluorometric analysis. Maternal plasma selenium concentrations (Se-Bm) were significantly greater than fetal concentrations (Se-Bc). Placental selenium (Se-Pl) levels were four times that of fetal levels. Variability of Se-Bc is best explained by placental concentrations. Maternal weight and ethnic origin are significantly correlated with Se-Bc. Female newborn have higher selenium levels than male newborn. The present study demonstrates the significance of the placenta as an indicator of fetal selenium exposure.
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D Campagna, D Mergler, G Huel, S Bélanger, G Truchon, C Ostiguy, D Drolet (1995)  Visual dysfunction among styrene-exposed workers.   Scand J Work Environ Health 21: 5. 382-390 Oct  
Abstract: OBJECTIVES--The present study was undertaken to examine the relation between visual functions and occupational exposure to styrene. METHODS--A total of 128 workers (85% of the total population), from three glass-reinforced plastics plants in Canada, agreed to participate in the study. Environmental and biological measures were made on the day(s) prior to the assessment of near visual acuity (National Optical Visual Chart), chromatic discrimination (Lanthony D-15 desaturated panel), and near contrast sensitivity (Vistech 6000). The analyses were performed on 81 workers with near visual acuity of at least 1 min of arc at 0.5 m. RESULTS--The subjects were relatively young [29 (SD 8) years], with little seniority [5 (SD 4) years]. Styrene exposure for 8 h ranged from 6 to 937 (first quartile 21 mg.m-3, third quartile 303 mg.m-3), depending on the job site. The end-shift concentrations of urinary mandelic acid ranged from nondetectable to 1.90 mmol.mmol creatinine-1. Significant positive relations were found between the internal and external styrene exposure measurements and color vision loss adjusted for age, alcohol consumption, and seniority in a multiple regression analysis. The multiple regression analysis is also showed that the end-shift concentration of urinary mandelic acid was inversely related to contrast sensitivity at 6 and 12 cycles.degree-1. Logistic multiple regression models indicated that the end-shift concentration of urinary mandelic acid was related to the prevalences of blurred vision, tearing, and eye irritation. CONCLUSIONS--These findings suggest that there is a positive relation between styrene exposure and early color and contrast vision dysfunction.
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D Campagna, D Mergler, A Picot, J Sahuquillo, S Belanger, C Pleven, A Brun, M P Leclerc-Marzin, G Lamotte, G Huel (1995)  Monitoring neurotoxic effects among laboratory personnel working with organic solvents   Rev Epidemiol Sante Publique 43: 6. 519-532 Dec  
Abstract: The relationship between organic solvent exposure and central nervous disorders make early detection of neurophysiologic et neuropsychologic alterations in organic solvent exposed workers a priority. Moreover, the variability in the frequency of exposure and the numerous organic solvents encountered in scientific laboratories render the environmental and biological measurements used in medical surveys almost impossible. The present study was undertaken to appreciate the potential neurotoxic effects of organic solvents handling in laboratory employees. Neurophysiological and neuropsychological tests batteries were used with each worker and data were adjusted for potential confounding factors (age and education level). A Principal Components Analysis were performed to reduce the information and the first five factors corresponded to: mood states, speed coding, contrast vision in high frequencies, manual dexterity and contrast vision in low frequencies. These five factors were compared between the daily manipulators of at least one solvent (n = 75) and the non or occasional solvent users (n = 35). The results from this study showed that subjects directly in contact with solvents had a poorer mood state than those who were not or rarely exposed (p < 0.01) and that independently of the "work activity". Mood state impairment in chronic solvent exposed workers has been shown by many authors, with or without psychomotor alteration, and may reflect possible over-exposure. Detection of this instability may lead to early neurophysiologic alteration in exposed workers and permit health services to intervene before the development of irreversible effects.
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1994
D Mergler, G Huel, R Bowler, A Iregren, S Bélanger, M Baldwin, R Tardif, A Smargiassi, L Martin (1994)  Nervous system dysfunction among workers with long-term exposure to manganese.   Environ Res 64: 2. 151-180 Feb  
Abstract: Neurological disorders, bearing many similarities to Parkinson's disease, have been associated with environmental and occupational exposure to manganese (Mn). To document early nervous system dysfunction associated with long-term exposure to Mn, a battery of neurofunctional tests was administered to workers employed in Mn alloy production. Study participation was 95% (n = 115). A matched pair design was used; actively working men, with no history of workplace exposure to neurotoxins, were recruited from the region as referents. Matching was done on the variables: age (+/- 3 years), educational level (+/- 2 years), smoking status, and number of children. Stationary environmental sampling indicated that Mn levels varied widely (geometric means: Mn dust, 0.89 mg/m3; respirable Mn, 0.04 mg/m3). The alloy workers had significantly higher levels of whole blood Mn (geometric mean: 1.03 microgram/100 ml vs 0.68 microgram/100 ml); no differences were observed for urinary Mn. Univariate analysis (paired t test, Signed Rank and McNemar) and multivariate analysis of variance (Hotelling-Lawley statistic) revealed that the pairs differed on symptom reporting, emotional state, motor functions, cognitive flexibility, and olfactory perception threshold; verbal fluency, basic mathematics, reading capability, and attentional capacity were similar. These findings are consistent with current knowledge on brain Mn activity and suggest that manifestations of early manganism can be observed in well designed population studies, using sensitive testing methods.
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R M Bowler, D Mergler, G Huel, J E Cone (1994)  Aftermath of a chemical spill: psychological and physiological sequelae.   Neurotoxicology 15: 3. 723-729  
Abstract: Psychological, and psychophysiological sequelae were studied in a community which had experienced a railroad chemical spill of 19,000 gallons of the toxic pesticide metam sodium. Information was collected on 350 persons living in the area of the spill (spill residents) and 114 nonexposed controls, recruited using a randomized sampling strategy, from a nearby similar, but unexposed control town. Psychological measures used were the MMPI-2, POMS, IES Scale, Environmental Worry, Perceived Social Support and Perceived Control Scale. Physiological measurements were two measurements of blood pressure, pulse, and salivary cortisol level, taken both at the beginning and the conclusion of the study. Demographic and medical information was asked in a Questionnaire. Results indicate greater levels of depression, anxiety, and somatic symptoms in the spill residents in addition to greater environmental worry and lower perceived social support. Spill odor perception was related to increased psychological and physiological sequelae. The spill residents had higher blood pressure and less fluctuation of cortisol levels than the controls. Comparison of spill residents who were litigants and those who were not, indicates no differences for blood pressure, pulse, and cortisol, MMPI-2, Environmental Worry and the Control Scale. Litigants scored slightly higher on the IES, Intrusion and the POMS scales. No dose/response relationship between distance to the river and evacuation status was obtained. The chemical spills was associated with a wide variety of psychological and physiological reactions.
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R M Bowler, D Mergler, G Huel, J E Cone (1994)  Psychological, psychosocial, and psychophysiological sequelae in a community affected by a railroad chemical disaster.   J Trauma Stress 7: 4. 601-624 Oct  
Abstract: Psychological, psychosocial, and psychophysiological sequelae were studied in a community which had experienced a railroad chemical spill of 19,000 gallons of the toxic pesticide metam sodium. Two hundred twenty exposed residents were compared to 114 controls and paired on age, education, gender, race, and number of children. A clinical interview and physiological measurements (blood pressure, pulse, and cortisol level) were taken, the MMPI-2, IES Scale, Mood Scale, Environmental Worry, Perceived Social Support, and Perceived Control Scale and a questionnaire were administered. Results indicated greater levels of depression, anxiety, and somatic symptoms in the spill residents in addition to greater environmental worry and lower perceived social support. Spill residents had higher blood pressure and less fluctuation of cortisol levels than controls. No difference on litigation status was obtained except on the IES, Intrusion and the POMS scales. Chemical disasters are associated with a wide variety of psychological, psychosocial, and physiological distress.
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1993
N Fréry, C Nessmann, F Girard, J Lafond, T Moreau, P Blot, J Lellouch, G Huel (1993)  Environmental exposure to cadmium and human birthweight.   Toxicology 79: 2. 109-118 Apr  
Abstract: Fetal toxicity of cadmium (Cd) is well documented in rodents. However, little information is available regarding the human fetus. To investigate the effect of low levels of Cd on the human placenta and the consequences on birthweight, we conducted a study of 102 mothers and their newborns in an obstetrical care unit. Placental and hair samples were collected at delivery to determine Cd concentrations. The main finding of this study was the relationship between a decrease in birthweight and an increase of newborn hair Cd which varied in the presence of placental calcification. In cases of parenchymal calcifications, placental Cd levels were higher (Wilcoxon test, P < 0.05) and newborn hair Cd levels were lower (Wilcoxon test, P < 0.01) than in the absence of calcification. These relationships remained significant even after taking into account smoking habits and gestational age. In the presence of calcification, an increase in the level of Cd in newborn hair was related to a decrease in birthweight which was independent of placental Cd concentration (rpartial = -0.49, P < 0.01). In the absence of calcification, a decrease in birthweight was observed for the upper values of newborn hair Cd (r = -0.44, P < 0.05 when Cd > or = 0.3 ppm). The difference in birthweight between infants in the first and last quartiles of newborn hair Cd was 472 g in cases of calcifications and 122 g in the absence of calcification. Other placental parameters were not significantly related to placental Cd concentration.
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G Huel, J Godin, N Frery, F Girard, T Moreau, C Nessmann, P Blot (1993)  Aryl hydrocarbon hydroxylase activity in human placenta and threatened preterm delivery.   J Expo Anal Environ Epidemiol 3 Suppl 1: 187-199  
Abstract: Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta has been well documented. This enzyme may be induced by a variety of Polycyclic Aromatic Hydrocarbons (PAHs) and the AHH inducibility is associated with harmful effects of environmental chemicals. Toxic effects of PAHs in tissues such as placenta have been demonstrated to be due to their metabolites, epoxides, which interact with DNA. Thus, environmental PAHs may be related to its alterations in fetal development. Founded on these findings the PAH metabolites could interfere with the normal course of the pregnancy and may be an aborticide, a teratogen or a carcinogen. We hypothesize that low increased activity of placental Aryl Hydrocarbon Hydroxylase (AHH) may be an important determinant of human fetotoxicity. The present investigation was designed to examine the possible implications of PAH exposure at environmental exposure levels on the normal course of the pregnancy using AHH induction as an indicator of PAH exposure. Threatened Preterm Delivery (TPD) was used as an index of problems in the normal course of pregnancy. A group of forty pregnancies at term with TPD was compared with eighty controls for placental AHH induction. Macroscopic placental examination was also performed. A significant increase in prevalence of placental AHH induction with TPD was shown (Odds-Ratio = 2.8; 95% confidence bounds [1.3-6.2]; chi 2 = 6.7 p < 0.01). No such increases were found associated with placental pathology. When taking into account the group of placenta without basal plate calcifications, the significant increase in prevalence of placental AHH induction with TPD above mentioned was greatly increased (Odds-Ratio = 8.9; 95% confidence bounds [2.4-32.9]; chi 2 = 11.1 p < 0.001) controlling for gestational age. The increase in prevalence of placental AHH induction with TPD disappeared when taking into account the subgroup with basal plate or parenchyma calcifications. It is hypothesized that the high estrogen and progesterone at term may explain these associations.
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1992
G Huel, P Tubert, N Frery, T Moreau, J Dreyfus (1992)  Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years.   Neurotoxicology 13: 1. 249-254  
Abstract: A prospective study has been carried out to assess the psychomotor deficit resulting from a moderate decrease in gestational age and pre-natal lead exposure. The general cognitive index of the McCarthy psychometric scale (adjusted for confounders) in six-year-old children was related to gestational age. Most of the psychomotor scores showed smoothing variations with gestational age ranging from 37 to 39 weeks, whereas sharp changes occurred between 39 to 40 weeks, with plateau values above such a cut-off for all spheres of development examined. Maternal hair lead content, used as an indicator of lead exposure during pregnancy, was found to be negatively related to general cognitive, verbal, quantitative, and memory subscales (p less than 0.01), whereas its relationship with perceptual and motor subscales was close to 0.05 significance level. Control for gestational age did not change the significance level of the associations. When controlling for maternal hair lead levels, the significance of the association between gestational age and the McCarthy subscales also remained stable, only the general cognitive index and verbal subscale reaching the conventional significance level.
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G Huel, F Girard, C Nessmann, J Godin, P Blot, G Bréart, T Moreau (1992)  Placental aryl hydrocarbon hydroxylase activity and placental calcifications.   Toxicology 71: 3. 257-266  
Abstract: Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta as a result of maternal exposure to polycyclic aromatic hydrocarbons contained in cigarette smoke has been well documented. Furthermore, calcifications are more prevalent in the placentas of pregnant smokers than in those of non-smokers. The present study examines whether this latter relationship could be explained by the induction of AHH activity in the placenta. AHH levels were determined at birth in 141 unselected pregnant women admitted for delivery. Macroscopic placental examination was performed for vascular lesions, abnormalities of placental shape, of the cord and parameters of placental maturity such as basal and parenchymatous calcifications. Significant increases in the prevalence of calcifications of the placental basal plates and parenchyma with the induction of placental AHH were found. A similar significant association between smoking and AHH activation was also observed. These findings remained unchanged when controlling for smoking status assessed both by questionnaire and presence of cotinine in mother's urine. Moreover, the apparent association between smoking 'factor' and calcifications disappeared when controlling for AHH induction. Therefore, the association between smoking and placental calcifications previously related could be mediated by the AHH induction.
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N Fréry, G Huel, M Leroy, T Moreau, R Savard, P Blot, J Lellouch (1992)  Vitamin B12 among parturients and their newborns and its relationship with birthweight.   Eur J Obstet Gynecol Reprod Biol 45: 3. 155-163 Jul  
Abstract: Vitamin B12 (Cobalamin) is an essential nutrient in the diet of humans, particularly during pregnancy, nevertheless very few epidemiological studies have been reported, particularly concerning variation factors. The purpose of this study is to assess the role of vitamin B12 on birthweight after taking into account potential confounders, such as obstetrical, socioeconomic, and biological factors which will be identified. This study was conducted on 188 single births occurring during a 5-month period in an obstetrical care unit in Paris. Vitamin B12 plasma levels and folate plasma levels of mothers and cords along with haematological parameters were measured. Social and obstetrical features of the mothers as well as their tobacco exposure and alcohol consumption were recorded. Cord blood vitamin B12 levels were highly correlated with maternal levels (r = 0.63, P less than 0.001) and were 2-3-fold higher. Three variation factors of vitamin B12 were identified: maternal age, ethnicity and tobacco exposure. Negative correlations between birthweight and vitamin B12 levels were observed only among the smoker group (r mothers = -0.46, P less than 0.05 and r cords = -0.42, P less than 0.05). After adjustment for ethnicity and parity, birthweight remained negatively linked to vitamin B12 in smokers. This relationship could suggest that the availability of vitamin B12 for fetal development depends on certain biological factors present only in mothers who smoked. We hypothesized this relationship could be explained, in part, by lipid metabolism, particular to smokers.
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1991
R M Bowler, D Mergler, G Huel, R Harrison, J Cone (1991)  Neuropsychological impairment among former microelectronics workers.   Neurotoxicology 12: 1. 87-103  
Abstract: Although chemicals posing potential neurotoxic hazards are commonly used in the microelectronics industry, there has been no systematic study of possible chronic nervous system effects in microelectronics workers. The objective of the present study was to assess neuropsychological functions of a group of former microelectronics plant assembly workers and a group of referents, using a matched pair design. During employment, the former microelectronics workers had been exposed to multiple organic solvents, including trichloroethylene, xylene, chlorofluorocarbons and trichloroethane. Referents were recruited from the same geographic region. From a pool of 180 former workers and 157 referents, 67 pairs were matched on the basis of age, sex, ethnicity, educational level, sex and number of children. Comparison of results on the subtests of the California Neuropsychological Screening Battery-Revised (CNS-R) revealed significantly lower performance by the former microelectronics workers on tests of attention/concentration, verbal ability, memory functions, visuospatial functions, visuomotor speed, cognitive flexibility, psychomotor speed, and reaction time (t-test for pairs or Wilcoxon Signed Rank p less than 0.05). No significant differences were observed for performance on tests assessing mental status, visual recall, tactile function and learning. This overall pattern of impairment is consistent with organic solvent-related chronic toxic encephalopathy, and possible early stages of dementia. These findings underline the need for more studies among workers currently or previously employed in microelectronics industries.
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D Mergler, G Huel, R Bowler, B Frenette, J Cone (1991)  Visual dysfunction among former microelectronics assembly workers.   Arch Environ Health 46: 6. 326-334 Nov/Dec  
Abstract: Although known neurotoxins with potential ophthalmotoxic properties are commonly used in microelectronics assembly, there has been no systematic study of visual disturbances among past or present workers in this industry. The objective of the present study was to compare visual functions, using a matched-pair design, between former workers from a microelectronics plant and a local reference population. From an initial population of 180 former workers and 157 potential referents, 54 pairs were matched for age (+/- 3 y), education (+/- 2 y), sex, ethnic origin, and number of children. Near and far visual acuity, chromatic discrimination, and near contrast sensitivity were assessed monocularly. Paired comparisons (Signed-rank Wilcoxon test) revealed that the former microelectronics workers had significantly lower contrast sensitivity, particularly in the intermediate frequencies, independently of near visual acuity loss. There were no differences for far visual acuity in both eyes. Even though near visual acuity and color vision were compromised among the former workers, the differences were only significant for one eye, as was the prevalence of acquired dyschromatopsia (chi-square for matched pairs, p less than .001). These findings suggest a pattern of contrast sensitivity deficits consistent with impairment to foveal and/or neuro-optic pathways among these former microelectronics workers. Exposure to ophthalmotoxic chemicals is proposed as the most probable risk factor.
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1990
S Hajem, T Moreau, P Hannaert, J Lellouch, G Orssaud, G Huel, J R Claude, R P Garay (1990)  Erythrocyte cation transport systems and plasma lipids in a general male population.   J Hypertens 8: 10. 891-896 Oct  
Abstract: The relationships between five erythrocyte cation transport systems (Na(+)-K+ pump, Na(+)-K+ cotransport, Na(+)-Li+ countertransport and Na+ and K+ passive permeabilities) and plasma lipids (total plasma cholesterol, high-density lipoprotein cholesterol and triglycerides) were investigated in 129 male adult subjects with no known history of hypertension. Na+ and K+ erythrocyte contents were also considered for their possible relationships with plasma lipids. Na(+)-K+ cotransport and passive Na+ permeability were both significantly correlated with plasma triglycerides. Conversely, no significant correlation was found between erythrocyte cation transport systems or erythrocyte cation contents and total cholesterol. These findings suggest that plasma lipids can modulate erythrocyte ion transport activity in the general population.
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G Huel, D Mergler, R Bowler (1990)  Evidence for adverse reproductive outcomes among women microelectronic assembly workers.   Br J Ind Med 47: 6. 400-404 Jun  
Abstract: Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents.
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S Hajem, T Moreau, P Hannaert, J Lellouch, G Huel, G Hellier, G Orssaud, J R Claude, B Juguet, B Festy (1990)  Influence of environmental lead on membrane ion transport in a French urban male population.   Environ Res 53: 2. 105-118 Dec  
Abstract: Red cell cation transports (Na(+)-K+ pump, Na(+)-K+ cotransport system, Na(+)-Li+ countertransport, and Na+ and K+ passive permeabilities) and blood and hair lead levels were measured in 129 healthy adult Caucasians not occupationally exposed to lead. In agreement with previously reported in vitro results showing a lead-induced Na(+)-K+ ATPase inhibition, Na(+)-K+ pump activity was inversely correlated with hair lead (r = -0.18, P less than 0.05); it was not significantly correlated with blood lead. Na(+)-K+ cotransport activity was inversely correlated with blood lead contents (r = -0.23, P less than 0.05) but not with hair lead. No significant correlation was found between the remaining cation transport pathways and lead levels. It is hypothesized that environmental, long-term exposure to lead may result in pump inhibition, while a recent exposition to lead may result in inhibition of the Na(+)-K+ cotransport system. Further research is required in order to determine if red cell Na(+)-K+ pump and Na(+)-K+ cotransport activities are sensitive indicators of chronic and recent exposures to lead, respectively.
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1989
G Huel, J Godin, T Moreau, F Girard, J Sahuquillo, G Hellier, P Blot (1989)  Aryl hydrocarbon hydroxylase activity in human placenta of passive smokers.   Environ Res 50: 1. 173-183 Oct  
Abstract: The levels of smoke components and metabolites in maternal blood and urine are useful in assessing direct exposure but they do not appear to be sufficiently sensitive as a long-term indicator of passive smoke exposure. Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta as a result of maternal smoking has been well documented. This enzyme oxidizes various polycyclic aromatic hydrocarbons abundantly present in cigarette smoke. We hypothesized that passively inhaled tobacco smoke may induce placental AHH activity. Placental AHH levels were determined in 207 pregnancies at birth. As has been found in previous studies, we demonstrated that smoking during pregnancy is associated with a marked increase in placental AHH activity. A relationship was found between the recorded number of cigarettes smoked per day and the placental AHH activity. Moreover, AHH activity was significantly higher in pregnant women passively exposed to tobacco smoke relative to controls. The usefulness of analysis of placental AHH activity as a biological marker of in utero smoke exposure in epidemiological studies is considered.
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1988
T Moreau, P Hannaert, G Orssaud, G Huel, R P Garay, J R Claude, B Juguet, B Festy, J Lellouch (1988)  Influence of membrane sodium transport upon the relation between blood lead and blood pressure in a general male population.   Environ Health Perspect 78: 47-51 Jun  
Abstract: Five red blood cell cation transport systems (RBCTS), together with blood lead level and blood pressure, were measured in 129 male adult subjects who were not occupationally exposed to lead or subsequent to a course of treatment for hypertension. Blood lead was positively related with systolic blood pressure, and to a lesser degree with diastolic blood pressure. Blood lead was found significantly negatively related to one of the RBCTS, Na+,K+ cotransport, and in addition, Na+,K+ cotransport appeared negatively related to blood pressure. Final results showed that blood lead no longer accounts for an increase in systolic blood pressure when Na+,K+ cotransport was taken into account; the same trend was observed with diastolic blood pressure. These findings suggest that a blood lead-related Na+,K+ cotransport impairment could explain the blood pressure increase observed to parallel the blood lead increase.
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P A Hannaert, T Moreau, G Huel, G Orssaud, J Lellouch, J R Claude, J Sahuquillo, R P Garay (1988)  Blood pressure and erythrocyte Na+ transport systems in a French urban male population.   J Hypertens 6: 11. 905-911 Nov  
Abstract: This paper reports an investigation of blood pressure (taken as a continuous variable) as a function of: erythrocyte Na+ content; Na+,K+ pump; Na+,K+ cotransport and Na+,Li+ countertransport fluxes, and passive cation permeabilities in fresh erythrocytes from 129 French males who were living in an urban area and were not under treatment for any medical condition (after allowing for the effects of age, body mass index, alcohol and tobacco consumption). In contrast with previous findings in a North American population, we were unable to confirm that blood pressure was correlated with erythrocyte Na+ content and Na+,K+-AT-Pase activity. Conversely, the only transport parameter correlated (negatively) with blood pressure was outward Na+,K+ cotransport [r = -0.20, P less than 0.05 and r = -0.19, P less than 0.05, for systolic (SAP) and diastolic arterial pressure (DAP), respectively; n = 114]. When allowing for age, body mass index and alcohol consumption, the correlation coefficient between the Na+,K+ cotransport system and blood pressure increased from -0.20 to -0.28 (P less than 0.01) for SAP and from -0.19 to -0.28 (P less than 0.01) for DAP (n = 105). We conclude that the correlations between blood pressure and erythrocyte Na+ transport function could differ between North American and French (or Mediterranean) populations. In any case, a decreased pump or outward Na+,K+ cotransport activity may lead hypertensive subjects to a similar increase in cell Na+ (and Ca2+) content in the vascular wall.
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1986
C Bonithon-Kopp, G Huel, T Moreau, R Wendling (1986)  Prenatal exposure to lead and cadmium and psychomotor development of the child at 6 years.   Neurobehav Toxicol Teratol 8: 3. 307-310 May/Jun  
Abstract: In 1977, a hair sample was taken from 26 newborn babies and their mothers and analysed for lead and cadmium. Six years later, each of these 26 children was given a psychometric test (McCarthy Scales of Children's Abilities). Statistical analysis shows a significant negative relationship between the degree of in utero exposure to cadmium and lead and the child's motor and perceptual abilities. Any effect on memory or verbal skills was not statistically significant. Allowing for the confounding variables does not consistently affect these results.
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C Bonithon-Kopp, G Huel, C Grasmick, H Sarmini, T Moreau (1986)  Effects of pregnancy on the inter-individual variations in blood levels of lead, cadmium and mercury.   Biol Res Pregnancy Perinatol 7: 1. 37-42  
Abstract: Blood samples to be analysed for lead, cadmium and mercury were taken from 417 pregnant women not occupationally exposed to these metals. Each subject was paired with a non-pregnant woman of the same age (+/- 2 years), socio-economic status, alcohol and tobacco status. Most of the inter-individual variations observed in earlier studies were confirmed in the control group. Among the pregnant women, however, such variations in blood metal levels appeared to be somewhat different compared to the control women according to the parameters studied: age of the women, alcohol and tobacco consumption. Furthermore, the study of the evolution of blood levels of lead, cadmium and mercury throughout pregnancy revealed a significant decrease in cadmium levels during the first half of pregnancy. A similar tendency was observed for lead but this did not attain statistical significance.
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G Huel, C Boudène, M Jouan, P Lazar (1986)  Assessment of exposure to lead of the general population in the French community through biological monitoring.   Int Arch Occup Environ Health 58: 2. 131-139  
Abstract: The aim of the council directive of 29 March 1977 of the European Community (1) is the screening for non-work-related lead exposure levels in the general populations of European (member) countries. In France, such testing was carried out in eight metropolitan areas (having more than 500,000 inhabitants), another eight "critical" areas surrounding industrial emission sources and one area (Vosges) having a high level of lead contamination in the water. In view of the reference values (maximum 35 micrograms/dl in an individual blood sample) adopted by the directive, the situation is most serious in the area where the exposure is due to the lead contamination in the water. Individuals here run a seven times greater risk of exceeding the 35 micrograms/dl blood-lead limit relative to urban populations where the lead comes mostly from vehicle emissions into the atmosphere (i.e. 9.3% of the blood-lead values of the Vosgian sample exceed 35 micrograms/dl; 3.5% for the industrial complexes which deal with lead and 1.4% for the urban zone). While these vehicle exhausts are the subject of much current concern, in perspective, the problem of lead pipe contaminated drinking water appears to be of far greater importance.
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G Huel, J F Petiot, P Lazar (1986)  Algorithm for the grouping of contiguous geographical zones.   Stat Med 5: 2. 171-181 Mar/Apr  
Abstract: In geographical epidemiology, the correlation between two variables is often studied, using as basic units those zones for which these variables are available. However, because of their geographical contiguity, it could be misleading to consider each of these zones as independent statistical units. Moreover, spatial distributions (either of the factor or of the disease) are often distributed in relatively simple patterns; these patterns may induce strong correlations. Thus, the general pattern of the spatial distribution of the variables should be investigated before any attempt to infer epidemiological interpretation of a relationship. This paper presents an algorithm to construct contiguous groupings which are similar enough with regard to one of the two variables considered and to thus divide the original set of geographical areas into contrasting zones. The algorithm is easy to compute and allows mapping of the geographical distribution of the variable studied. It also lessens the risk of duplication of basic information by reducing the autocorrelation of one of the variables.
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1985
C Grasmick, G Huel, T Moreau, H Sarmini (1985)  The combined effect of tobacco and alcohol consumption on the level of lead and cadmium in blood.   Sci Total Environ 41: 3. 207-217 Mar  
Abstract: This study deals with the person-to-person variation in the levels of lead and cadmium in the blood of 6437 subjects (2883 men and 3554 women). The lead level (Pb-B) is clearly higher in men than in women, and the cadmium level (Cd-B) is a little higher in men than in women. Only the Pb-B varies according to age for both sexes. The results reveal that the consumption of alcohol could play an important part in the variation of lead and cadmium levels in the blood; the consumption of alcohol is associated with an increase in Pb-B but a decrease in Cd-B. These variations involving alcohol consumption remain significant regardless of smoking habits. On the other hand, an increase in Pb-B and Cd-B has been noted among smokers and, to a lesser degree, among former smokers, compared with non-smokers.
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1984
G Huel, R B Everson, I Menger (1984)  Increased hair cadmium in newborns of women occupationally exposed to heavy metals.   Environ Res 35: 1. 115-121 Oct  
Abstract: Newborn and maternal hair samples were obtained from subjects occupationally exposed to heavy metals and from matched controls. The geometric means of levels of cadmium and lead in hair from exposed mothers and of cadmium in hair from transplacentally exposed newborns were twice as high as levels present in samples from controls. There was a positive correlation between levels of cadmium in maternal and newborn's hair, but no such correlation for lead. Despite statistically significant evidence of increased exposure to cadmium, no adverse health effects were documented in the small group of exposed newborns included in this study. Problems associated with exogenous contamination of hair by heavy metals and potential advantages of hair sampling for measuring fetal exposures to heavy metals are discussed.
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1981
L Awad, G Huel, P Lazar, C Boudene (1981)  Factors of interindividual variations of blood lead levels (author's transl)   Rev Epidemiol Sante Publique 29: 2. 113-124  
Abstract: The blood lead levels of 1.877 persons living in 8 large French cities or in their suburbs were measured. Blood lead level varies with sex, age, tobacco, wine consumption and date of construction of the house. The specific effect of each of these variables can be quantified. The slope of the regression of blood lead level on age is approximatively 1 microgram/dl per 14 years. Blood lead level increases by 1 microgram for people living in houses built before 1945. The effect of tobacco and wine consumption is greater among males than females. For males the increase is about 3 microgram/dl between non smokers and heavy smokers whereas for females it is about 2 microgram/dl. Wine effect is about 2 microgram/dl among males and 1 microgram/dl among females. These findings are discussed in terms of differences in lead supply or modifications in the number and condition of red blood cells.
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G Huel, C Boudene, M A Ibrahim (1981)  Cadmium and lead content of maternal and newborn hair: relationship to parity, birth weight, and hypertension.   Arch Environ Health 36: 5. 221-227 Sep/Oct  
Abstract: Head hair samples were taken from 110 mothers and their newborns at delivery and analyzed for cadmium and lead content. Positive association for cadmium content, but not lead, was found between mothers and newborns. Correlation between the two metals was observed in the babies' hair. Lead levels in the mothers' hair were higher in mothers of parity three or greater than in primiparous mothers. Inverse relationships were found (1) between the cadmium content in babies' hair and their birthweight and (2) between the lead content in mothers' hair and the babies' gestational age. Cadmium levels in babies of hypertensive mothers were 3 times as high as in the hypertensive mothers themselves. A possible change in the permeability of the placenta during pregnancy was postulated.
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1978
G Huel, R Thomazeau, F Derriennic, P Lazar (1978)  Water hardness and cardiovascular mortality. A study of 947 alsatian communities (author's transl)   Rev Epidemiol Sante Publique 26: 5. 381-390  
Abstract: In Alsace (France) drinking water is supplied from two different sources. This situation is favourable to study the effects on human health of various water characteristics, among which hardness. However it would be misleading to consider the 947 towns or villages as independent units of observation because of their geographical adjacencies. An aggregation algorithm of these units has been set up. It consists in a progressive regrouping of adjacent areas, similar "enough" from the point of view of the parameters studied, the aim of the procedure being to get final areas with contrasted values of water characteristics. This partition is then used to compute rank correlation coefficients between water parameters and various mortality rates. With this method, no significant correlation was found between water hardness and mortality, in spite of the existence of a sharp gradient of hardness.
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G Huel, F Derriennic, P Ducimetière, P Lazar (1978)  Water hardness and cardiovascular mortality. Discussion of evidence from geographical pathology (author's transl)   Rev Epidemiol Sante Publique 26: 4. 349-359 Dec  
Abstract: The existence of a significant negative correlation between hardness of drinking water and mortality rates from cardiovascular disease has been established by numerous authors. The intensity of this relationship varies according to the country concerned, the size of the areas studied, and the confounding factors taken into consideration. Nevertheless, the problem concerning the interpretation of the correlation has not yet been resolved. In particular the methodological problem resulting from the contiguity of the geographic units has been generally neglected. It is shown that these difficulties weaken the conviction that the relationship is a causal one.
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1977
C Rumeau-Rouquette, J Goujard, G Huel (1977)  Possible teratogenic effect of phenothiazines in human beings.   Teratology 15: 1. 57-64 Feb  
Abstract: A prospective survey was carried out by the French National Institute of Health and Medical Research (INSERM) in 12 University hospitals in Paris and included 12,764 women; 189 gave birth to babies with unequivocal, non-chromosomally based, malformations. There was a significant excess of malformed infants when women had taken phenothiazines during the first three months after the last menstrual period. This association did not seem due to chance or to bias and could not be explained by the influence of the outcome of previous pregnancies. These data are to be added to results of recent surveys showing a significant increase of malformations in children exposed in utero to anticonvulsants, carbamates, benzodiazepines, tricyclic antidepressants, and amphetamines.
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1976
1975
1974
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