Blood pressure and erythrocyte Na+ transport systems in a French urban male population.

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.

Erythrocyte cation transport systems and plasma lipids in a general male population.

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.

Influence of membrane sodium transport upon the relation between blood lead and blood pressure in a general male population.

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.

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.

Environmental exposure to cadmium and human birthweight.

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.

Placental aryl hydrocarbon hydroxylase activity and placental calcifications.

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.

Neuropsychological impairment among former microelectronics workers.

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.

Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years.

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.

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.

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.

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.

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.

Aryl hydrocarbon hydroxylase activity in human placenta and threatened preterm delivery.

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.

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.

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.

Vitamin B12 among parturients and their newborns and its relationship with birthweight.

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.

The combined effect of tobacco and alcohol consumption on the level of lead and cadmium in blood.

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.

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.

[Water hardness and cardiovascular mortality. Discussion of evidence from geographical pathology (author's transl)]. / Dureté de l'eau et mortalité cardiovasculaire. Analyse critique des arguments de pathologie géographique.

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.