Estimation of Dermal Exposure to Volatile Organic Compounds (VOCs) from Feminine Hygiene Products: Integrating Measurement Data and Physiologically Based Toxicokinetic (PBTK) Model

Abstract

Background: An increasing number of studies have reported noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs).

Objectives: This study sought to address the gap in understanding the absorption, distribution, metabolism, and excretion dynamics of dermal exposure to VOCs from FHPs and to identify chemicals and products that could cause significant body burden.

Methods: We used measured contents of eight widely present VOCs across five categories of FHPs to estimate dermal exposure, and applied a physiologically based toxicokinetic (PBTK) modeling approach to elucidate VOC toxicokinetics in human body tissues. Inhalation exposure estimates were derived from 20 air samples collected via passive sampling and analyzed using a thermal desorption system coupled with gas chromatography-mass spectrometry. Predicted urinary VOC concentrations based on dermal and inhalation exposure were validated against 99 measurements from 25 females.

Results: Via skin absorption, the estimated levels of most target VOCs in nearly all tissues, except adipose and the rest of the body, rapidly peaked within an hour of product use. Specifically, $p$-cymene was estimated to reach $\sim 2.23\text{ng}/\mathrm{mL}$ in adipose tissue before decreasing over several hours due to efficient excretion pathways, including liver metabolism and exhalation. The model estimated that although the majority of absorbed VOCs (78.9%) were eliminated via liver metabolism, exhalation, and urine excretion, VOCs with $\log K_{\text{ow}}$ higher than 3.5, such as $p$-cymene, hexane, and $n$-nonane, exhibited a potential cumulative trend in adipose tissue. This trend resulted in the estimated VOC concentrations in adipose tissue being 1 to 4 orders of magnitude higher than those estimated in other tissues. In certain cases, $n$-nonane posed a potential noncancer risk (up to 0.07), and benzene presented a notable cancer risk (up to $1.82\times {10}^{-7}$), primarily attributed to washes and moisturizers, respectively.

Discussion: These findings reveal potential significant body burden and health risks associated with dermal exposure to VOCs from FHPs, warranting further research and regulatory measures. Comprehensive assessment of internal exposure by integrating with toxicokinetic modeling to elucidate chemical distribution in various tissues is recommended, rather than by measuring only one type of biomarker, to illustrate exposure variances and ensure accurate risk assessment. https://doi.org/10.1289/EHP15418.

Figure 1.

The schematic study design. The image in the figure was taken by the authors, and the graphics were created using Adobe Illustrator 2020 (Adobe Inc.). Note: $C_{\text{AT}}$, $C_{\mathrm{B}}$, $C_{\text{RB}}$ and $C_{\text{urine}}$, chemical concentration in the adipose tissue, blood, rest of body and urine, respectively; $K_{\text{renal}}$, the renal excretion coefficient; $P_{\text{adipose}/\text{blood}}$ and $P_{\text{rest\hspace{0.17em}of\hspace{0.17em}body}/\text{blood}}$, partition coefficients of corresponding tissues to blood; $Q_{\text{AT}}$, $Q_{\mathrm{K}}$ and $Q_{\text{RB}}$, blood flow to adipose tissue, kidney and rest of body, respectively; $V_{\text{AT}}$ and $V_{\text{RB}}$, volume of adipose tissue and rest of body; $V_{\text{urine}}$, volume of urine produced per unit time.

Figure 2.

Schematic diagram of PBTK model implemented in this study. Concentrations in skin and lung (in dashed boxes) were not predicted, and they are shown in the schematic diagram to indicate the exposure routes. Note: $C_{\mathrm{B}}$, chemical concentration in blood; $K_{\mathrm{m}}$, Michaelis constant; $K_{\mathrm{p}}$, permeability coefficient; $K_{\text{renal}}$, the renal excretion coefficient; PBTK, physiologically based toxicokinetic; $Q_{\text{AT}}$, $Q_{\mathrm{C}}$, $Q_{\mathrm{K}}$, $Q_{\mathrm{L}}$, and $Q_{\text{RB}}$, blood flow to adipose tissue, cardiac output, kidney, liver, lung and rest of body, respectively; $Q_{\mathrm{P}}$, alveolar ventilation volume per hour; $v_{\text{max}}$, maximum biotransformation rate in liver.

Figure 3.

(A) The estimated skin absorption amount dynamics of eight target VOCs from four categories of feminine hygiene products during a 28-d menstrual cycle. (B) Contribution dynamics of four categories of feminine hygiene products to the estimated skin absorption amounts of eight target VOCs during a 28-d menstrual cycle. All the data are shown in Supplemental Excel Tables S2–S3. Note: VOC, volatile organic compound.

Figure 4.

(A) Sankey diagram illustrating the relative contributions of VOCs absorbed from four categories of feminine hygiene products during the first 28-d menstrual cycle and their distribution in human body at the end of a menstrual cycle based on PBTK model. (B) Scatter diagram between $\log K_{\text{ow}}$ and proportion in adipose after skin absorption of VOCs from four categories of feminine hygiene products during the first 28-d menstrual cycle and the trend line based on PBTK model. The correlation was tested by Spearman analysis. All the data are shown in Supplemental Excel Tables S4–S5. Note: $\log K_{\text{ow}}$, logarithm of the octanol-water partition coefficient; PBTK, physiologically based toxicokinetic; VOC, volatile organic compound.

Figure 5.

(A) VOC concentration dynamics in different tissues using four categories of feminine hygiene products in the first 8 h of a menstrual cycle based on PBTK model. (B) VOC concentration dynamics in different tissues using four categories of feminine hygiene products during 28 d of a menstrual cycle based on PBTK model. All the data are shown in Supplemental Excel Table S6. Note: PBTK, physiologically based toxicokinetic; VOC, volatile organic compound.

Figure 6.

VOC concentration dynamics in urine using individual feminine hygiene products during first 8 h of menstrual period based on PBTK model. All the data are shown in Supplemental Excel Table S7. Note: PBTK, physiologically based toxicokinetic; VOC, volatile organic compound.

Figure 7.

(A) Comparison of the estimated and measured VOC concentrations in urine. The estimates were derived from using best-guess exposure scenario with both dermal exposure from using feminine hygiene products and inhalation exposure from indoor air, with the error bars showing the highest and lowest exposure scenarios. These estimates correspond to the mean levels in 505th to 512th h, the 73rd to 80th h, the 169th to 176th h, and the 337th to 344th h of the 28-d menstrual cycle in the model. The measurements ($n=25$ for each mean value, except $n=24$ for the first time point) were from the urine of 25 females collected at four time points: 7 d before menstruation and 3, 7, and 14 d after the first day of menstruation. Each dot (mean with SD) in the comparison represents the value at each time point. (B) Uncertainty analysis results of urinary concentrations using probability bounds analysis based on PBTK model. The column is the estimated concentration using best-guess exposure scenario with both dermal exposure from using feminine hygiene products and inhalation exposure from indoor air. The minus bar indicates the lowest exposure scenario when using 95th body weight value among the US females 20–29 y of age, the associated kinetic and physiological data, and only one-fourth exposure dose. The plus bar indicates the highest exposure scenario when using fifth body weight value among the US females 20–29 y of age, the associated kinetic and physiological data, and double exposure dose. All the data are shown in Supplemental Excel Tables S9–S10. Note: PBTK, physiologically based toxicokinetic; SD, standard deviation; VOC, volatile organic compounds.