title: In vitro dermal penetration of 4-chloro-3-methylphenol from commercial metal working fluid and aqueous vehicles.
abstract: The biocide 4-chloro-3-methylphenol (CMP, CAS number 59-50-7) is a common additive to metal-working fluids (MWF) and building materials. National Institute for Occupational Safety and Health (NIOSH) researchers previously identified and quantified CMP in a commercial water-soluble MWF, TRIM VX, and demonstrated irritancy and sensitization potential of both TRIM VX and CMP alone after dermal exposure in a murine model. In the current study, the in vitro human epidermal permeability of CMP contained in a working dilution of TRIM VX (20% in water) was evaluated and, for comparison, permeability from an aqueous buffer was also assessed. CMP penetration was also measured from transient exposures to 20% TRIM VX. To address differences in penetration rates from 20% TRIM VX and from buffer, the role of thermodynamic activity of CMP in the 2 vehicles on dermal penetration was investigated. Static headspace gas chromatography was used to measure vapor pressures and infer fractional thermodynamic activities of CMP in the mixtures. Permeability coefficient (k(p)) of CMP from 20% TRIM VX was (4.1 +/- 0.8) x 10(-3) cm/h (mean +/- SD, n = 5), and CMP was found at a concentration of 3555 +/- 191 microg/ml in this donor. In contrast, k(p) was 0.18 +/- 0.03 cm/h (n = 5) at a similar concentration (3919 +/- 240) from buffer donor. Steady-state fluxes from 20% TRIM VX and buffer were comparable when expressed as functions of thermodynamic activity of CMP in the donor, rather than as concentrations. Transient (20 or 40 min) exposures of epidermal membranes to 20% TRIM VX (n = 4) resulted in total penetration of 4.2 +/- 1.2 and 7.3 +/- 0.8 microg/cm(2), respectively; these amounts are comparable to amounts predicted using a simple algebraic equation.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA. HFrasch@cdc.gov
authors.forename: H Frederick
authors.initials: HF
authors.lastname: Frasch
authors.forename: Lun-Yi
authors.initials: LY
authors.lastname: Zang
authors.forename: Ana M
authors.initials: AM
authors.lastname: Barbero
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D002849:Chromatography, Gas; D003408:Cresols / Q000493:pharmacokinetics*; D020405:Dermis / Q000378:metabolism*; D004202:Disinfectants / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008420:Manufactured Materials / Q000032:analysis; D008670:Metals / Q000737:chemistry*; D008875:Middle Aged; D016273:Occupational Exposure; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D012869:Skin Absorption / Q000502:physiology*; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry; D055815:Young Adult
chemical_list: D003408:Cresols; D004202:Disinfectants; D008670:Metals; D014677:Pharmaceutical Vehicles; D012996:Solutions; D014867:Water; C006984:chlorocresol