Abstract
1,2-Benzisothiazolin-3-one (BIT) is a commonly used organic biocide containing an isothiazolone ring. However, it may have adverse effects on human health and its risk needs to be properly evaluated. Dermal exposure is the main route of BIT exposure, and co-exposed substances may affect its absorption. The dermal permeation profile of BIT has not been well-studied. This study aimed to investigate the dermal permeation profiles of BIT with or without cosmetic use. Dermal permeation profiles of BIT were investigated after infinite- (100 μg/cm2), or a finite-dose (10 μg/cm2) application with or without cosmetics using a minipig skin and Strat-M®, an artificial membrane. A cream, lotion, and essence (namely, face serum) were pre-treated as representative cosmetics on minipig skin for 30 min, with BIT treatment afterward. After the treatment, BIT left on the skin surface was collected by cotton swabbing, BIT in the stratum corneum, by sequential tape stripping, and BIT retained in the remaining skin was extracted after cutting the skin into pieces before LC-MS/MS analysis. When an infinite dose was applied, permeation coefficients (Kp, cm/h) for minipig skin and Strat-M® were 2.63 × 10−3 and 19.94 × 10−3, respectively, reflecting that skin permeation was seven to eight times higher in Strat-M® than in the minipig skin. BIT, in the presence of cosmetics, rapidly permeated the skin, while the amount in the stratum corneum and skin deposit was reduced. We performed a risk assessment of dermally applied BIT in the absence or presence of cosmetics by calculating the skin absorption rate at 10 h based on the toxicological data from several references. The risk level was higher in the presence of essence as compared to lotion, which was higher than cream, which was higher than the control (non-treated). However, all of the margins of safety values obtained were greater than 100, suggesting that BIT is safe for use in dermally exposed consumer products. We believe that this research contributes to a greater understanding of the risk assessment of isothiazolinone biocides.
Highlights
Isothiazolone biocides are widely used in a variety of industrial water treatment applications to control microbial growth and biofouling [1]
We aimed to use in vitro approaches to determine the profile of percutaneous absorption of BIT using a minipig skin and Strat-M® membrane based on OECD Test guidance
The permeation coefficient (Kp ) of BIT was calculated as the percutaneous penetration index when an infinite dose was applied
Summary
Isothiazolone biocides are widely used in a variety of industrial water treatment applications to control microbial growth and biofouling [1]. Many factors play important roles in dermal absorption, including the molecular weight and charge of the chemical ingredient, lipophilicity of the formulation, thickness of keratin and constituents (dependent on the body part), duration of exposure, area of the skin onto which a chemical was applied, the concentration of application, other substances pretreated on the skin, and other factors [18]. The use of skin-care products, including cream, lotion, and essence, is one of the significant factors affecting dermal absorption. Many of these products contain chemicals that enhance dermal penetration [19]. Hoffman et al showed that the dermal absorption of harmful substances in several products increases after the use of hand sanitizers [19], indicating a significant impact of skincare products on the skin penetration of harmful chemicals. We studied the effect of skincare products (cream, lotion, and essence (or face serum)) pretreatment on the dermal absorption of BIT, and conducted a risk assessment of dermally exposed BIT with or without skincare products
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