In utero exposure to lead and cord blood total IgE. Is there a connection?

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.

[Biological materials collection within population of pregnant women at delivery]. / Recueil de tissus biologiques au sein d'une population de femmes parturientes.

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.

Evolution of blood lead levels in urban French population (1979-1995).

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.

Color vision and occupational toluene exposure.

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.

Does selenium reduce the risk of threatened preterm delivery associated with placental cytochrome P450-1A1 activity?

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.

Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns.

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.

Environmental lead exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in maternal and cord blood.

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.

Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters.

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.

Head circumference at birth and maternal factors related to cord blood total IgE.

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.

Epidemiological health study of a town exposed to chemicals.

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.

Symptom base rates after chemical exposure for white, Hispanic and African-Americans.

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.

Surveillance of early neurotoxic dysfunction.

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.

Color vision loss among styrene-exposed workers neurotoxicological threshold assessment.

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.

[Monitoring neurotoxic effects among laboratory personnel working with organic solvents]. / Appréciation d'effets neurotoxiques associés à l'utilisation des solvants organiques chez les personnels de laboratoire.

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.

Visual dysfunction among styrene-exposed workers.

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.

Inter-individual variation of selenium in maternal plasma, cord plasma and placenta.

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.

Psychological, psychosocial, and psychophysiological sequelae in a community affected by a railroad chemical disaster.

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.

Nervous system dysfunction among workers with long-term exposure to manganese.

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.

Aftermath of a chemical spill: psychological and physiological sequelae.

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.