Probabilistic pharmacokinetic modeling of airborne lead corresponding to toxicologically relevant blood lead levels in workers

Sweeney, Lisa

doi:10.1016/j.yrtph.2021.104894

Regulatory Toxicology and Pharmacology

2021

DOI: 10.1016/j.yrtph.2021.104894

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Probabilistic pharmacokinetic modeling of airborne lead corresponding to toxicologically relevant blood lead levels in workers

Lisa Sweeney

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Cited by 6 publications

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References 21 publications

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“…The DoD-O'Flaherty biokinetic model, 35,36 based on a model first developed by O'Flaherty, differed from the Leggett+ model by relying on somewhat different physiological assumptions and by considering the impact of a worker's birth year and accumulated lifetime lead exposure to assess the impact of adult workplace lead exposure. It predicted the blood lead distribution that would have existed in the DoD workforce on January 1, 2018, had the current DoD workforce, composed of men and women of various ages, been historically exposed full time to specified levels of airborne lead since they were 18 years of age.…”

mentioning

confidence: 99%

ACOEM Position Statement

Kosnett¹,

Berenji²,

Burton³

et al. 2023

J Occup Environ Med

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mentioning

confidence: 99%

ACOEM Position Statement

Kosnett¹,

Berenji²,

Burton³

et al. 2023

J Occup Environ Med

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Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace – Part II adjustments to the adult exposure model, confirmation of Leggett+, and modeling of workplace exposure

Vork

Brown

Carlisle

2023

Journal of Occupational and Environmental Hygiene

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Rapid Review of Dermal Penetration and Absorption of Inorganic Lead Compounds for Occupational Risk Assessment

Niemeier

Maier²,

Reichard

2021

Annals of Work Exposures and Health

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Lead (Pb) exposure continues to be a significant public health issue in both occupational and non-occupational settings. The vast majority of exposure and toxicological studies have focused on effects related to inhalation and gastrointestinal exposure routes. Exposure to inorganic Pb compounds through dermal absorption has been less well studied, perhaps due to the assumption that the dermal pathway is a minor contributor to aggregate exposures to Pb compounds. The aim of this rapid review was to identify and evaluate published literature on dermal exposures to support the estimation of key percutaneous absorption parameters (Kp, flux, diffusion rate) for use in occupational risk assessment. Eleven articles were identified containing information from both in vitro and in vivo systems relevant to percutaneous absorption kinetics. These articles provided 24 individual study summaries and information for seven inorganic Pb compounds. The vast majority of study summaries evaluated (n = 22, 92%) reported detectable amounts of dermal absorption of inorganic Pb. Data were identified for four Pb compounds (Pb acetate, Pb nitrate, Pb oxide, and Pb metal) that may be sufficient to use in evaluating physiologically based pharmacokinetic models. Average calculated diffusion rates for the pool of animal and human skin data ranged from 10−7 to 10−4 mg cm−2 h−1, and Kp values ranged from 10−7 to 10−5 cm h−1. Study design and documentation were highly variable, and only one of the studies identified was conducted using standard test guideline-compliant methodologies. Two studies provided quality estimates on the impacts of dermal absorption from water-insoluble Pb compounds on blood Pb levels. These two studies reported that exposures via dermal routes could elevate blood Pb by over 6 µg dl−1. This estimation could represent over 100% of 5 µg dl−1, the blood Pb associated with adverse health effects in adults. The utility of these estimates to occupational dermal exposures is limited, because the confidence in the estimates is not high. The literature, while of limited quality, overall strongly suggests inorganic Pb has the potential for dermal uptake in meaningful amounts associated with negative health outcomes based on upper bound diffusion rate estimates. Future standard test guideline-compliant studies are needed to provide high-confidence estimates of dermal uptake. Such data are needed to allow for improved evaluation of Pb exposures in an occupational risk assessment context.

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Probabilistic pharmacokinetic modeling of airborne lead corresponding to toxicologically relevant blood lead levels in workers

Cited by 6 publications

References 21 publications

ACOEM Position Statement

ACOEM Position Statement

Evaluation and updates to the Leggett model for pharmacokinetic modeling of exposure to lead in the workplace – Part II adjustments to the adult exposure model, confirmation of Leggett+, and modeling of workplace exposure

Rapid Review of Dermal Penetration and Absorption of Inorganic Lead Compounds for Occupational Risk Assessment

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