Pharmacokinetics of transdermal methyl-, ethyl-, and propylparaben in humans following single dermal administration

Mi-Yeon Shin; Jeong Weon Choi; Seungho Lee; Sungmin Kim; Younglim Kho; Kyungho Choi; Sungkyoon Kim

doi:10.1016/j.chemosphere.2022.136689

Pharmacokinetics of transdermal methyl-, ethyl-, and propylparaben in humans following single dermal administration

Chemosphere. 2023 Jan:310:136689. doi: 10.1016/j.chemosphere.2022.136689. Epub 2022 Oct 8.

Authors

Mi-Yeon Shin¹, Jeong Weon Choi², Seungho Lee³, Sungmin Kim⁴, Younglim Kho⁴, Kyungho Choi⁵, Sungkyoon Kim⁶

Affiliations

¹ Graduate School of Public Health, Seoul National University, Seoul, South Korea; Office of Dental Education, School of Dentistry, Seoul National University, Seoul, South Korea.
² Graduate School of Public Health, Seoul National University, Seoul, South Korea.
³ Department of Preventive Medicine, College of Medicine, Dong-A University, Busan, South Korea.
⁴ Department of Health, Environmental and Safety, School of Human and Environmental Sciences, Eulji University, Seongnam-si, Gyeonggi-do, South Korea.
⁵ Graduate School of Public Health, Seoul National University, Seoul, South Korea; Institute of Health and Environment, Graduated School of Public Health, Seoul National University, Seoul, South Korea.
⁶ Graduate School of Public Health, Seoul National University, Seoul, South Korea; Institute of Health and Environment, Graduated School of Public Health, Seoul National University, Seoul, South Korea. Electronic address: ddram2@snu.ac.kr.

PMID: 36220432
DOI: 10.1016/j.chemosphere.2022.136689

Abstract

Parabens are common chemicals used as preservatives in foods, cosmetics, and personal care products. Although transdermal exposure to parabens occurs, studies on human pharmacokinetics (PK) following dermal exposure to parabens are scarce. In this study, the PK following dermal exposure to parabens was determined and compared with our previous findings on oral exposure. A paraben mixture cream containing 0.8% deuterated methyl-, ethyl-, and propylparaben (MeP-d₄ 0.26%; EtP-d₄ 0.26%, and PrP-d₄ 0.28%) was dermally applied to the whole arm of five male volunteers at a dose of 24 g/person over 30 min. Blood and urine samples were collected at several intervals over the course of 48 h to measure the levels of MeP-d₄, EtP-d₄, and PrP-d₄ and their conjugated metabolites using HPLC-MS/MS. As a result of non-compartmental analysis, the average peak values of total (sum of conjugated and unconjugated metabolites) MeP-d₄, EtP-d_4, and PrP-d₄ were reached at 7.8 h, 10.5 h, and 5.3 h, indicating a slower absorption rate compared to that of oral exposure (<2 h). The terminal elimination half-lives of MeP-d₄, EtP-d₄, and PrP-d₄ were 12.2 h, 12.0 h, and 9.3 h, respectively. Fractional urinary excretion (F_ue) of total MeP-d₄, EtP-d₄, and PrP-d₄ was 1.7%, 2.3%, and 1.9%, respectively. The F_ue of total and unconjugated PrP-d₄ following dermal exposure was five times lower and three times higher, respectively, compared with those after oral exposure, suggesting that PrP is relatively less metabolized to the conjugated form after dermal exposure. Taken together, dermal exposure to paraben leads to a longer apparent half-life and results in higher proportions of biologically active unconjugated parabens in the systemic circulation as compared to oral exposure. This study provides insights into the kinetic properties of parabens and their metabolites in humans.

Keywords: Dermal exposure; Methylparaben; Paraben; Pharmacokinetics; Propylparaben.

MeSH terms

Administration, Cutaneous
Cosmetics* / analysis
Environmental Exposure / analysis
Humans
Male
Parabens* / analysis
Tandem Mass Spectrometry

Substances

propylparaben
Parabens
Cosmetics