Using physiologically-based pharmacokinetic modeling to assess the efficacy of glove materials in reducing internal doses and potential hazards of N-methylpyrrolidone during paint stripping

The Toxic Substances Control Act (TSCA) empowers the EPA to regulate chemical substances. In 2015, the USEPA released a risk assessment for NMP in paint strippers, utilizing PBPK modeling and considering PPE like gloves to reduce exposure. While the EPA found glove use effective, they didn't evaluate specific glove efficacy, highlighting the need for this study. The efficacy of glove materials in preventing NMP permeation varies significantly, spanning almost three orders of magnitude in measured permeation rates. The USEPA's assessment identified eight occupational scenarios with unacceptable hazard (MOE < 30), motivating this refined risk assessment to quantify the protection offered by different glove materials using PBPK modeling within the USEPA's defined exposure scenarios. This study aims to improve the risk assessment by focusing on the efficacy of different glove types in reducing the potential hazards.

Several studies investigated NMP permeation through various glove materials. Zellers and Sulewski [2] assessed temperature dependence, finding butyl rubber gloves impermeable. Stull et al. [3] evaluated glove resistance to multi-chemical paint strippers, identifying butyl rubber and plastic laminate as most effective. Crook and Simpson [4] tested 20 glove types, also concluding butyl rubber and laminate gloves provided the best protection. These studies showed permeation rates varying widely across glove materials, underscoring the need for a comprehensive evaluation of glove efficacy in reducing NMP exposure.

This study utilized USEPA's margin of exposure (MOE) approach: MOE = IDTA/IDEA, where IDTA is the internal dose at the point of departure (POD) from toxicity assessment, and IDEA is the internal dose from the exposure assessment. USEPA's toxicity assessment for NMP, focusing on developmental effects, was unchanged. Acute exposure used peak blood concentration (Cmax), while chronic exposure used area under the curve (AUC) in blood. The eight occupational scenarios with MOE < 30 from the USEPA assessment were reassessed. Three glove categories were established based on NMP permeation rates: minimal, moderate, and maximal protection. NMP steady-state permeation rates from the literature were converted to permeability coefficients (Kp) using equation (2). The net permeability coefficient for gloved hands (Kpnet) was calculated using equation (3), accounting for both skin and glove permeability. The PBPK model was used to simulate NMP internal doses for each glove category in the eight scenarios, with and without respirators. Glove protection factor (PF) was calculated (equation 4) by comparing internal doses with and without gloves for the dermal liquid pathway alone.

The reassessment using PBPK modeling and considering different glove materials revealed significant differences in the effectiveness of the protective equipment. For acute exposures, moderate protection gloves resulted in acceptable MOE values (≥30) for half of the scenarios, while maximal protection gloves resulted in acceptable MOEs for all scenarios. For chronic exposures, maximal protection gloves resulted in acceptable MOE values for all but one scenario. The calculated glove protection factors (PFs) ranged widely from 1.1 to 1900, demonstrating a substantial variation in the degree of protection offered by different glove materials depending on the glove material, NMP formulation and internal dose measure. These findings highlight the importance of selecting appropriate PPE based on the specific exposure scenario and the type of NMP formulation used.

This refined risk assessment demonstrates the significant impact of glove material selection on reducing NMP exposure during paint stripping. The large range of protection factors emphasizes the critical need for selecting appropriate gloves based on the specific work task and NMP concentration. The results support the use of NMP-containing paint strippers when proper PPE, especially gloves with maximal protection, are used. This study provides crucial data to support risk-reduction strategies, such as improved product labeling and MSDS instructions emphasizing suitable glove materials, offering viable alternatives to a complete NMP ban under TSCA.

This study provides a refined risk assessment for NMP exposure during paint stripping, highlighting the critical role of glove selection in mitigating hazards. The findings support the continued use of NMP in paint strippers with appropriate PPE, emphasizing the need for clear guidelines on glove material selection based on NMP formulation and exposure scenario. Future research could focus on evaluating the long-term durability and degradation of different glove materials under actual working conditions, and on assessing the permeation of NMP through different glove types under varied environmental conditions and prolonged exposures.

The study relies on permeation data from previous studies which may not perfectly represent real-world scenarios, and the accuracy of predictions depends on the accuracy of the PBPK model parameters and assumptions. There is a potential for variability in glove performance due to differences in manufacturing and quality control. Also, the study focused solely on the dermal exposure pathway and did not account for any potential synergistic effects from co-exposure to other chemicals. Additional research is needed to fully characterize the impact of all potential exposure routes under different working conditions.