This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for these toxic substances described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. CAS# 7439-92-1

https://stacks.cdc.gov/view/cdc/37676/cdc_37676_DS1.pdf

Toxicological Profile for Lead

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

/pdf/pb-neurotoxicity-neuropsychological-effects-of-lead-toxicity-5hjafm7t6k.pdf

Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

Purpose To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments. Patients and Methods Patients with breast cancer exposed to chemotherapy (n = 60; mean age, 51.7 years) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1, 6, and 18 months after treatment. Patients not exposed to chemotherapy (n = 72; mean age, 56.6 years) and healthy controls (n = 45; mean age, 52.9 years) were assessed at matched intervals. Results Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains. For Processing Speed, a three-way interaction among treatment group, age, and baseline cognitive reserve (P < .001) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy (P = .003) and controls (P < .001). A significa...

/pdf/longitudinal-assessment-of-cognitive-changes-associated-with-3v2asyab4n.pdf

Longitudinal Assessment of Cognitive Changes Associated With Adjuvant Treatment for Breast Cancer: Impact of Age and Cognitive Reserve

Pb Neurotoxicity: Neuropsychological Effec ts of Lead Toxicity

Background: In the United States, one in six children are affected by neurodevelopmental disorders, and polybrominated diphenyl ethers (PBDEs) in flame-retardant chemicals are measured ubiquitously...

/pdf/developmental-pbde-exposure-and-iq-adhd-in-childhood-a-2mdyb500si.pdf

Developmental PBDE Exposure and IQ/ADHD in Childhood: A Systematic Review and Meta-analysis

To assess the effects of low-level organic solvent exposure on olfactory function, a cross-sectional study in paint manufacturing workers was undertaken. Workers in two paint manufacturing facilities (N = 187) were tested using the University of Pennsylvania Smell Identification Test (UPSIT), a standardized, quantitative test of olfactory function. Industrial hygiene air samples over the past 13-15 years revealed that average solvent exposures in these plants were 2-40% of the existing threshold limit values for the three chemicals measured. Stratification by smoking status revealed evidence of dose-related decrements in olfactory function (p = .01) only in non-smokers. Furthermore, those nonsmoking workers in the highest exposure category had UPSIT scores below the fifth percentile for their age. These results suggest that solvents may cause nervous system dysfunction at lower levels than previously suspected, and that the olfactory system may be a critical target organ for the neurotoxic effects of solvents and other chemicals.

Solvent‐associated decrements in olfactory function in paint manufacturing workers

The goals were to determine if lead exposure is associated with cerebral white matter changes (WMC) and if so, does WMC mediate the relation between lead and psychomotor slowing as measured by Grooved Pegboard (GP). In the literature, age is the strongest predictor of WMC and therefore 61 lead smelter workers age 50 and under were included in the study population. Mean (range) age was 40 (23-50) years, years of education was 9 (0-13), duration of employment was 19 (1-26), current blood lead (PbB) was 29 (16-42) μg/dl, working lifetime weighted integrated blood lead (IBL) was 826(65-1451) μg year/dl, working lifetime weighted average blood lead (TWA) was 42 (17-59) μg/dl, and bone lead (PbBn) was 39 (-12-90) μg Pb/g bone mineral. WMC, recorded as hyperintensities on T2-weighted MRI of the brain were graded. Lead variables were entered in a logistic regression attempting to differentiate normal versus abnormal MRI, after controlling for age and cerebrovascular risk factors. Direct effects of lead on GP and indirect effects of lead on GP through WMC was modeled using multiple linear regression analyses after controlling for the covariates. WMC were present in 23% of MRIs. Logistic regression of WMC on lead exposure metrics demonstrated significantly elevated odds ratios for IBL, TWA, and PbBn after the covariates. Of the lead exposure variables, IBL (β = 0.339, p < 0.10) had a larger direct effect on GP after adjusting for the covariates than PbBn (β = 0.265, p < 0.10). After adjusting for the lead term and covariates WMC accounted for an additional effect on GP performance after PbBn (β = 0.261, p < 0.10) and after IBL (β = 0.278, p < 0.05). Path analysis demonstrated that some of the relationship of both PbBn and IBL with GP is mediated by WMC.

The association of lead exposure and motor performance mediated by cerebral white matter change.

Background: Cognitive reserve (CR)—a construct studied in many neurologic disorders—refers to the maintenance of cognitive performance in spite of ongoing underlying brain pathology. Objective: We hypothesized that a dose-effect relationship would exist between chronic occupational lead exposure and cognitive effects in workers with low CR but not in workers with high CR and identical lead exposure, and that level of CR would not influence the relationship between lead exposure and motor performance. Methods: We stratified currently employed lead smelter workers by Wide Range Achievement Test-R for reading (WRAT), a recognized measure of CR, into loCR and hiCR groups. From these two groups we matched 56 pairs on working lifetime weighted blood lead (TWA). We performed a factor analysis on 14 neuropsychological outcome variables. Within each CR group regression analyses after adjusting for age, alcohol use, and depression scale score tested for dose-effect relationships between TWA and outcome variables. Results: Both CR groups had comparable age, years employed, alcohol use, and current blood lead levels. Factor analysis provided three factors and five tests used in the regression analyses. Significant dose-effect relationships between TWA and cognitive tests present only in the loCR group included Attention Factor and Digit Symbol. Both CR groups demonstrated significant dose-effect relationships on the Motor Factor. Conclusion: This study found that cognitive reserve protects against the effect of chronic lead exposure on select measures of cognitive performance but not on motor performance.

IMPACT OF COGNITIVE RESERVE ON THE RELATIONSHIP OF LEAD EXPOSURE AND NEUROBEHAVIORAL PERFORMANCE. Authors' reply

In this study we investigated the effect of recent and chronic lead exposure, and its interaction with ergonomic stressors, on peripheral nerve function In a cross-sectional design, we used retrospective exposure data on 74 primary lead smelter workers We measured blood and bone lead levels and, from historical records, calculated lead dose metrics reflecting cumulative lead exposure: working-lifetime integrated blood lead (IBL) and working-lifetime weighted-average blood lead (TWA) We additionally created five metrics related to IBL that cumulated exposure only above increasing blood lead levels ranging from 20 to 60 microg/dL (IBL20-IBL60) Current perception threshold (CPT) assessed large myelinated (CPT2000), small myelinated (CPT250), and unmyelinated (CPT5) sensory nerve fibers Using multiple linear regression, we modeled CPT on the different measures of lead dose after adjusting for relevant covariates CPT had a curvilinear relationship with TWA, with a minimum at a TWA of 28 microg/dL Both TWA and IBL accounted for a significant percentage of the variance of CPT2000 (DeltaR2 = 87% and 39%, respectively) As the criterion blood lead level increased from IBL20 through IBL60, so did the percentage of CPT2000 variance explained, with DeltaR2 ranging from 58% (p < 003) for IBL20 to 233% (p < 000) for IBL60 IBL60 also significantly contributed to the explanation of variance of CPT250 and significantly interacted with ergonomic stressors Measures of chronic blood lead exposure are associated with impairment of large and small myelinated sensory nerve fibers This effect is enhanced at the highest doses by ergonomic stressors

https://www.jstor.org/stable/pdfplus/3436743.pdf

Effect of lead exposure and ergonomic stressors on peripheral nerve function.

The effect of lead exposure on neurobehavioral performance is modified by age Whether educational achievement can serve as an effect modifier on the lead-cognitive performance relationship is examined The Mini-Mental State Examination (MMSE) and the reading section of the Wide Range Achievement Test-Revised (WRAT-R), a measure of educational achievement, were administered to 256 lead smelter workers The workers had a mean (standard deviation) age of 41 (79) years, education of 10 (28) years, employment duration of 17 (81) years, current blood lead of 28 (88) micrograms/dL, and working lifetime integrated blood lead index (IBL) of 725 (434) micrograms-yr/dL The median (range) MMSE score was 29 (19 to 30) Multiple linear regression assessed the contribution of age, WRAT-R, education, alcohol intake, cigarette use, IBL, and IBL x WRAT-R on MMSE performance A significant IBL x WRAT-R interaction examined by stratification found a significant dose-effect relationship between IBL and MMSE, but only in the 78 workers with a WRAT-R reading grade level below 6 years Workers with higher educational achievement compensated for the effect of lead on cognitive performance

The interaction of education and cumulative lead exposure on the Mini-Mental State Examination.

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