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Use of Generalized Additive Model to Detect the Threshold of ?-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.

ABSTRACT: BACKGROUND:Lead inhibits the enzymes in heme biosynthesis, mainly reducing ?-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of ?-aminolevulinic acid dehydratase activity reduced by lead exposure. METHODS:We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. ALAD activity was determined by the standardized method of the European Community. ALAD G177C (rs1800435) genotyping was conducted using the polymerase chain reaction and restricted fragment length polymorphism (PCR-RFLP) method. In order to find a threshold effect, we used generalized additive models (GAMs) and scatter plots with smoothing curves, in addition to multiple regression methods. RESULTS:There were 229 ALAD1-1 homozygotes and 9 ALAD1-2 heterozygotes identified, and no ALAD2-2 homozygotes. Lead workers had significantly lower ALAD activity than non-exposed workers (41.6 ± 22.1 vs. 63.3 ± 14.0 U/L, p < 0.001). The results of multiple regressions showed that the blood lead level (BLL) was an important factor inversely associated with ALAD activity. The possible threshold of BLL affecting ALAD activity was around 5 ?g/dL. CONCLUSIONS:ALAD activity was inhibited by blood lead at a possible threshold of 5 ?g/dL, which suggests that ALAD activity could be used as an indicator for lead exposure regulation.

SUBMITTER: Huang CC

PROVIDER: S-EPMC7460038 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Use of Generalized Additive Model to Detect the Threshold of δ-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.

Huang Chan-Ching CC Yang Chen-Cheng CC Liu Te-Yu TY Dai Chia-Yen CY Wang Chao-Ling CL Chuang Hung-Yi HY

International journal of environmental research and public health 20200807 16

<h4>Background</h4>Lead inhibits the enzymes in heme biosynthesis, mainly reducing δ-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure.<h4>Methods</h4>We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. ALAD activity was determined by the standardized method of the European Comm ...[more]

PMID: 32784669

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Project description:ObjectiveTo determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults.MethodsThe authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele.ResultsSixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status.ConclusionsAlthough not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak.

Project description:BackgroundExposure to lead (Pb) affects multiple health outcomes and physiological systems. In adults, even small increases in blood Pb levels have been associated with decreased glomerular filtration rate, increased risk of hypertension and increased incidence of essential tremor. To date, there have been few Pb-exposure assessments using the United States Occupational Health and Safety Administration (OSHA) regulations.ObjectiveThe aim of the present study was to assess Pb-exposure in terms of elevated blood lead levels (BLL) and urinary-δ-aminolevulinic acid (U-δ-ALA) levels of workers exposed to Pb in the lead acid battery industry in Tamil Nadu, India based on Pb exposure regulations set by the American Conference of Governmental Industrial Hygienists (ACGIH) and OSHA.Materials and methodsBLLs and U-δ-ALA were estimated in 449 male workers exposed to Pb across ten different job categories in a lead acid battery factory. Worker BLLs were estimated using atomic absorption spectrophotometry and U-δ-ALA was estimated using spectrophotometry.ResultsThe Biological Exposure Index of the American Conference of Governmental Industrial Hygienists (BEI-ACGIH) were used to assess Pb exposure. BLLs <30 μg/dL were found in 63.5% of workers, and 36.5% of workers had BLLs>30 μg/dL. The present study also assessed Pb exposure using OSHA regulations and found that 83.3% of workers had BLLs <40 μg/dL and 16.7% of workers had BLLs>40 μg/dL. Among these workers, 0.7% of workers had BLLs >60 μg/dL. An excessive excretion of U-δ-ALA (20-40 mg/L) was noted in pasting area workers (2.6%) followed by executives (2.2%) and assembly workers (0.9%).ConclusionsWorkers in the job categories of pasting and assembly, as well as executives, are at high risk of Pb exposure compared to other job categories. We recommend placing humidifiers on the roof and keeping a water bath closer the to plate cutting area to reduce fugitive Pb dust emissions. We recommended workers with BLLs >60 μg/dL be removed from jobs involving Pb exposure and return to work only when their BLLs are <40 μg/dL.Participant consentObtained.Ethics approvalThe study was approved by the ethics committee of the Regional Occupational Health Centre (Southern) Bengaluru, part of the National Institute of Occupational Health of India.Competing interestsThe authors declare no competing financial interests.

Dataset Information

Use of Generalized Additive Model to Detect the Threshold of ?-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.

Publications

Use of Generalized Additive Model to Detect the Threshold of δ-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.

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