In vivo genotoxic effects of smoking and occupational lead exposure in printing press workers

The objective of the present study was to evaluate the genotoxicity of a combination exposure to lead and smoking in workers from the printing industry and also to examine the possible interaction between the two agents. Individuals were classified into 4 different groups: control group, lead-exposed group, smokers and the double-exposure group. Chromosomal analysis was carried out according to conventional methods. Our preliminary study shows that lead-exposed individuals had a significantly increased frequency of sister chromatid exchanges. Further, double exposure to smoking and lead inhibits mitosis.     

Blood lead level and lead exposure of industrial workers in suburban Tokyo

Blood lead concentrations were determined at intervals between 1975 and 1980 from two groups of industrial workers, a group of highway repairmen, and workers from a lead-using electrical manufacturing plant in suburban Tokyo. The average blood lead content of the highway repairmen ranged from 9.6 ± 3.2 to 11.5 ± 4.7 μg/100 mol. The blood lead content of every factory worker employed as such for over 5 years was at least twice that of the highway repair crew members. Among the factory workers, variations in blood lead levels were greater between the workers in any given sampling period than those of an individual worker over the 5-year study period. The high, steady blood levels in the factory workers were attained within 6 months of employment.     

Effects of long-term lead exposure on monkey leukocyte chromosomes

Cynomolgus monkeys (Macaca irus) received daily doses of 1 or 5 mg of lead for a period of 12 months. Samples of venous blood were taken at 0, 7, 9 and 12 months, and cultured lymphocytes were analysed for the presence of chromosome aberrations. A few severe chromosome aberrations, such as dicentrics or translocations, appeared in the control animals as well as in the lead-treated ones, during the course of the experiment. However, lead treatment increased significantly the frequency of chromosome and chromatid gaps, and this result is in agreement with other previous results.     

A comparison of the diminution rates of lead in blood and lead mobilized by CaEDTA after termination of occupational exposure: a long-term observation in two lead workers

CaEDTA 20 mg/kg was administered weekly for 3.5 years after termination of occupational exposure to two lead workers. The diminution half-lives for lead in blood and urine lead mobilized by CaEDTA were 4.8 and 3.3 years respectively for subject 1 following 28 years exposure and 3.3 and 2.0 years respectively for subject 2 following 26 years exposure. The difference in the diminution rate between lead in blood and lead mobilized by CaEDTA was significant in subject 2 (p less than 0.05).     

Psychophysiologic effects of early lead exposure.

In several separate experiments neonatal rats were intubated daily with 9, 27 or 81 mg lead acetate/kg of body weight throughout their 3-week postnatal period of development. Based on average body weights, the total daily lead intake was 0.156, 0.454 or 1.384 mg lead per animal, respectively (in addition to normal lead intake from the environment). Subtle and specific behavioral changes, involving an inability to attenuate inappropriate behavior in a two-way shuttle or a habit-reversal operant task, occurred in offspring following exposure to a minimum of 0.454 mg lead per day. The specificity of this central dysfunction was such that motor activity was normal, stress responsiveness remained unaffected and simple learning ability was comparable to that of controls. The only indication of a central neurochemical modification accompanying this behavioral defect was a tendency for telencephalic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities to be depressed, suggesting a possible involvement of the cholinergic system. Steady-state levels of brain monoamines were unaltered. The experimental weanlings displayed an inhibition of blood delta-amino levulinic acid dehydratase (ALAD) activity, a parallel reduction in regional brain ALAD activity, a moderate reduction in hematocrit and hemoglobin and an increase in kidney weight. This latter effect occurred even at the lowest level of lead intake, 0.156 mg lead per day.     

Behavioral effects of nicotine exposure from secondhand tobacco smoke among bar and restaurant workers

This study explores the behavioral effects of nicotine exposure from secondhand tobacco smoke (SHS) on bar and restaurant workers. Baseline data were obtained from a longitudinal study of 105 bar and restaurant workers. Hair nicotine, self-reported SHS exposure, smoking status, symptoms of nicotine exposure after being exposed to a smoky environment, and nicotine dependence were assessed. Nonsmokers reporting four or more symptoms of nicotine exposure had higher hair nicotine levels than those reporting less than four symptoms. Nonsmokers with higher hair nicotine levels were 2.2 times more likely to report 4 or more behavioral symptoms. Self-reported secondhand tobacco smoke exposure and hair nicotine were not predictive of nicotine dependence among smokers. Nicotine exposure from secondhand tobacco smoke may have important behavioral outcomes in nonsmokers. This study provides further evidence for the importance of prohibiting smoking in hospitality venues to protect the health of workers.     

Behavioral effects of low level neonatal lead exposure

Rats exposed to lead via maternal milk were tested at various stages of development on a number of behavioral tasks. Beginning at paturition, the dams were given either tap water, 0.02%, or 0.10% lead acetate in the drinking water. Pups from all three groups were weaned to normal chow and tap water at 21 days of age. The mean lead concentration of the dam's blood and of neonatal (20 days of age) brain and blood were all below 50 microgram/100 ml. No significant differences were found between the high lead-exposed group and controls in general as measured by wheel running over a 21 day period beginning at 30 days of age. However, there was a significant difference in wheel running behavior during the first three hr of testing. Both lead-exposed groups were found to display significantly less aggressive behavior as measured by the shock-elicited aggression test. Low level lead exposure had no discernable effect on the acquisition and subsequent reversal of a successive brightness discrimination task. Lead exposure under these conditions appears to affect some aspects of emotional behavior, while having little effect on general activity or cognitive function.     

Neuropsychological effects of long-term exposure to organophosphate pesticides

Cholinesterase inhibitors, such as carbamates and organophosphates (OPs), are widely used as insecticides and pesticides and may be stored as biological weapons. The massive use of these products, along with a lack of personal protective equipment on the job, and accidental and intentional ingestions, has produced a great number of poisonings in farmers. A large part of the employment and income in southeastern Spain is concentrated in intensive greenhouse agriculture in which growers are exposed to a varying degree of subsymptomatic doses of a combination of pesticides, mainly OPs and carbamates. We conducted a cross-sectional survey of workers in high-exposure conditions to assess possible neurobehavioral deficits, using a wide array of tasks to test neuropsychological functioning and emotional status. Linear and logistic regression series revealed the importance of the variable "years working with pesticides" as a measure of cumulative exposure for risk of worsened perceptive function performance (odds ratio (OR)=6.93, 95% confidence interval (CI): 1.52-31.51), visuomotor praxis (OR=5.00, 95% CI: 1.22-20.40) and integrative task performance time (OR=4.12, 95% CI: 1.18-14.39) with no relation to plasma cholinesterase activity as a measure of recent exposure. This association was statistically significant after controlling for confounds (age and educational level). The findings showed association of long-term exposure and worse performance in neuropsychological functions, which is interpreted as evidence of a chronic effect of cumulative high exposure to OPs and carbamates.     

Neurobehavioral effects of a long-term exposure to tetraalkyllead

Employees of a factory producing antiknock additives for gasoline were examined psychologically after an exposure of an average of 14 years. A neurobehavioral symptom questionnaire, tests of single and choice reaction time, a cancellation task and a digit symbol test were the neurobehavioral variables. Total lead in urine and trimethyllead in urine showed different patterns of correlation with the neurobehavioral measures. Intellectual abilities (logical reasoning), age, and job years were controlled by partial correlation statistics as possible confounders. Referring to the low level of 21 μg lead per 100 ml blood and regarding the dose-response relations reported in the literature, the results support the hypothesis of a special neurotoxicity of the alkyllead compounds.     

Skeletal effects of developmental lead exposure in rats.

To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1)) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.     

Neurodevelopmental effects of postnatal lead exposure at very low levels

This study is among the first to examine specific neurobehavioral deficits in children exposed at very low lead levels. A systematic analysis for the presence of a threshold of lead exposure was conducted. The sample consisted of 246 African American, inner-city children from whom blood lead concentrations were assessed at 7.5 years of age. The results consistently show neurobehavioral deficits in relation to low levels of lead in the areas of intelligence, reaction time, visual-motor integration, fine motor skills, attention, including executive function, off-task behaviors, and teacher-reported withdrawn behaviors. Effects were identified in the specific domains of attention, executive function, visual-motor integration, social behavior, and motor skills, which have been previously suggested as part of lead's "behavioral signature". Visual inspection of nonparametric regression plots suggested a gradual linear dose-response relation for most endpoints. No threshold discontinuity was evident. Regression analyses in which lead exposure was dichotomized at 10 microg/dl were no more likely to be significant than analyses dichotomizing exposure at 5 microg/dl. Given that associations were found between lead levels as low as 3 microg/dl for multiple outcomes, these data provide additional evidence that there is no apparent lower bound threshold for postnatal lead exposure.     

Early behavioral effects of lead perinatal exposure in rat pups

Acoustic analysis of infants crying, a sensitive and selective index for measuring the effect of pre and perinatal lead exposure, may provide an early marker for central nervous system damage produced by the toxic. The present study evaluated the effects of exposure to low lead levels during perinatal and early postnatal periods on ultrasonic vocalization (USV), an early behavior of rat pups essential to their development. Non-sexually experienced females were gavaged daily with 8, 16 or 24 mg/kg of lead acetate or the control solution (1 ml/kg) for 30 days prior to breeding and until their pups were weaned. After crossover of dams, pups had been exposed to lead during pregnancy+lactation, pregnancy or lactation. The physiological variables measured on postnatal days 7 or 14 were USV, locomotion, rectal temperature, body weight and blood lead levels. Lead exposition during pregnancy+lactation, pregnancy or lactation induced a significant dose-dependent decrease of USV of 7-day-old pups. On the contrary, lead exposition during the different phases of pregnancy induced a significant dose-dependent increase of USV in 14-day-old rat pups. Blood lead levels varied from 5.7 to 36.5 microg/dl in pups. Body weight and temperature were not influenced by lead exposition. Lead-exposed 14-day-old pups were significantly more active. This study provides evidence of developmental changes in USV emission in rat pups exposed with low lead levels.     

Weight-of-evidence evaluation of long-term ozone exposure and cardiovascular effects

We conducted a weight-of-evidence (WoE) analysis to assess whether the current body of research supports a causal relationship between long-term ozone exposure (defined by EPA as at least 30 days in duration) at ambient levels and cardiovascular (CV) effects. We used a novel WoE framework based on the United States Environmental Protection Agency's National Ambient Air Quality Standards causal framework for this analysis. Specifically, we critically evaluated and integrated the relevant epidemiology and experimental animal data and classified a causal determination based on categories proposed by the Institute of Medicine's 2008 report, Improving the Presumptive Disability Decision-making Process for Veterans. We found that the risks of CV effects are largely null across human and experimental animal studies. The few positive associations reported in studies of CV morbidity and mortality are very small in magnitude, mainly reported in single-pollutant models, and likely attributable to bias, chance, or confounding. The few positive effects in experimental animal studies were observed mainly in ex vivo studies at high exposures, and even the in vivo findings are not likely relevant to humans. The available data also do not support a biologically plausible mechanism for the effects of ozone on the CV system. Overall, the current WoE provides no convincing case for a causal relationship between long-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation; thus, we categorize the strength of evidence for a causal relationship between long-term exposure to ozone and CV effects as “below equipoise.”     

Neurobehavioral effects of occupational exposure to acrylonitrile in Chinese workers

We examined neurobehavioral outcomes of Chinese workers exposed to acrylonitrile, a potentially neurotoxic substance. We used the WHO-recommended neurobehavioral core test battery to assess the neurobehavioral functions of all study subjects. We compared 81 workers in an acrylonitrile-monomer plant and 94 workers in an acrylic fibers plant with 174 workers with no workplace acrylonitrile exposure. Acrylonitrile workers reported increased tension, depression, anger, fatigue and confusion on the Profile of Mood States. Performances in the Simple Reaction Time, Digit Span, Benton Visual Retention and Pursuit Aiming II were also poorer among exposed workers compared to unexposed workers. Some of these poor performances in tests were also related to exposure duration. Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of neuropsychological impairment induced by exposure to acrylonitrile. Further studies are needed to characterize potential neurotoxicity from chronic and acute exposures to acrylonitrile.     

Effect of long-term exposure to pesticides on plasma esterases from plastic greenhouse workers

Previous reports in animals considered beta-glucuronidase activity as a novel biomarker of anticholinesterase (organophosphates and carbamates) pesticides exposure. Acid phosphatase activity was also shown to increase after organophosphates exposure. In addition, there is evidence that the paraoxonase status influences sensitivity to specific pesticides. In this study, activities of beta-glucuronidase, acid phosphatase, cholinesterase, and paraoxonase were measured in plasma from plastic greenhouse workers exposed over the long term to different pesticides, including organophosphates and carbamates, in order to evaluate the potential chronic toxicity of pesticides at occupational level. Our results show that activities of paraoxonase and cholinesterase were decreased in applicators of pesticides compared to non-applicators. Likewise, it was found that activities of beta-glucuronidase and acid phosphatase were associated with pesticide exposure in humans, and that both biochemical parameters were related to each other. Interestingly, the paraoxonase B allele (phenotyped in plasma) was associated with a higher risk of inhibition of cholinesterase activity above a 25% level, which supports the hypothesis that paraoxonase phenotypes are associated with susceptibility of humans to anticholinesterase pesticides toxicity.     

Neurotoxic effects of heavy lead exposure determined with psychological tests

Nine men exposed to high concentrations of lead in their work at a battery plant were examined with the aid of psychological tests. Intelligence tests indicated normal intellectual potential, but memory, attention, concentration and psychomotor performance were severely impaired. The clinical picture indicated an organic mental syndrome. Psychological tests are recommended for clinical evaluation of neurotoxic effects of lead exposure.     

Associations of lead exposure and dose measures with erythrocyte protein kinase C activity in 212 current Korean lead workers.

Lead can replace calcium in enzyme assays that measure protein kinase C activity and lead activates protein kinase C in human erythrocytes after exposure to lead in vitro. To examine the relevance of these observations to lead exposure in humans, we studied the associations of lead found in blood or tibia with activation of protein kinase C in erythrocytes isolated from workers in the lead industry. We examined erythrocytes among 212 lead workers, with a mean (+/-SD) age of 39.1 (10.0) years and exposure duration of 8.1 (6.5) years and measured protein kinase C activation by an in vitro back-phosphorylation assay. After adjustment for potential confounding factors (age and sex), tibia lead and exposure duration were significantly associated with erythrocyte protein kinase C activation (both p values < 0.05). No associations were observed between protein kinase C activation and blood-lead or zinc-protoporphyrin levels. These findings suggest that human exposure to lead results in activation of erythrocyte protein kinase C, which may be directly relevant to the neurotoxicity of lead.     

Manganese exposure and age: neurobehavioral performance among alloy production workers

Manganese (Mn) is associated with neurotoxic effects under certain conditions of exposure. A recent study on environmental Mn exposure showed an Mn × age interaction for several neurobehavioral functions. The objective of the present study was to examine the neurobehavioral test results in relation to age and Mn exposure, using an existing data set on 74 workers from an Mn alloy production plant and referents pair-matched for age (±3 years), educational level (±2 years), number of children, and smoking status. The pair differences between Mn-exposed workers and referents increased significantly with age for scores on Delayed Word Recall, Trail Making B, Cancellation H, Nine-Hole Hand Steadiness Test, and Vibratometer. These results suggest that for certain neurobehavioral functions, and in particular for information processing, Mn-related deficits increase with age. This outcome could not be explained by higher cumulative Mn exposure.     

Evaluation of lead exposure in battery‐manufacturing workers with focus on different biomarkers

The influence of exposure to lead on the frequency of micronuclei (MN), nuclear buds and nucleoplasmatic bridges was investigated in peripheral blood lymphocytes in 15 male battery‐manufacturing workers and 15 controls matched for age and smoking habits. In addition to MN test, blood lead (B‐Pb) and cadmium (B‐Cd), delta aminolevulinic acid dehydratase (ALAD) activity, erythrocyte protoporphyrin (EP), serum vitamin B₁₂ (S‐Vit B₁₂) and folate (S‐folate) were determined in all subjects. Lead‐exposed subjects had significantly higher MN frequency and B‐Pb concentrations than controls. In control smokers we found a significant negative correlation between B‐Pb concentration and frequency of nucleoplasmatic bridges, and nuclear division index. In control non‐smokers a significant positive correlation was observed only between age and nuclear buds frequency, and between S‐folate and B‐Pb level. In lead exposed smokers, significant positive correlations between MN frequency and S‐Vit B₁₂, S‐folate, and nuclear buds frequency were found. A positive correlation in exposed smokers was also found between nuclear buds frequency and S‐Vit B₁₂ concentration. A negative correlation was found between ALAD and EP, and B‐Pb in exposed smokers. Exposed non‐smokers showed significant negative correlation between MN frequency and B‐Cd, and ALAD and EP. The results indicate a genotoxicity of lead, pointing to a micronucleus assay as a relevant test for assessing genotoxic effects resulting from occupational exposure. The other indicators did not necessarily follow the results of THE MN test. Influence of smoking should be further investigated. Copyright © 2009 John Wiley & Sons, Ltd.     

Biochemical aspects of lead exposure in silver jewelry workers in western Maharashtra (India)

This study was conducted to examine the effect of blood lead (Lead) on heme biosynthesis, the hematopoietic system, oxidative stress, and antioxidant status of silver jewelry workers (SJW) in western Maharastra (India). The blood lead level of the SJW group (N = 30) was in the range of 30.2-64.7 microg dL(-1) (mean +/- SD, 48.56 +/- 7.39 microg dL(-1)), whereas that of non-occupational Lead-exposed normal healthy control subjects (N = 35) was 2.8-22.0 microg dL(-1) (mean +/- SD, 12.52 +/- 4.08 microg dL(-1)). Although the blood lead level of the SJW group increased significantly (p < 0.001) when compared with the control group, the urinary excretion of lead in the SJW group was not altered. In the SJW group, non-activated delta-aminolevulinic acid dehydratase (ALAD) activity significantly decreased (p < 0.05), and the ratio of activated/non-activated ALAD increased when compared with controls (p < 0.001), whereas activated ALAD activity was not altered significantly. Erythrocyte zinc protoporphyrin (ZPP) was not altered in SJW. The urinary excretion of delta-amino-levulinic acid (p < 0.001) and porpobilinogen (p < 0.05) of the SJW group increased significantly when compared with controls. Hematology parameters, such as the packed cell volume (p < .001) and total erythrocyte count (p < 0.05) significantly decreased, whereas the mean corpuscular hemoglobin concentration (p <.001) and total white blood cell count (p < .001) increased in the SJW group in comparison with controls. The serum malondialdehyde content significantly increased (p < .001), and the activities of antioxidant enzymes erythrocyte-SOD (p < .001), erythrocyte catalase (p < .05), and plasma ceruloplasmin (p < .001) significantly decreased in the SJW group compared with the controls. The results of the study clearly show an alteration of heme biosynthesis and cellular impairment of the pro-oxidants/antioxidants balance, resulting in oxidative damage in the silver jewelry workers group in western Maharashtra (India).