Isothiazolinone Detection in Dish Soap and Personal Care Products: Comparison of Lovibond Isothiazolinone Test Kit and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Isothiazolinones are commonly used preservatives, which may cause allergic contact dermatitis. The Lovibond Isothiazolinone Test Kit (LITK) has been reported to successfully identify clinically relevant, occult isothiazolinones in patient personal care products. OBJECTIVE: The aim of the study was to analyze dish soaps and personal care products that do not declare isothiazolinones ("no-ISO") for the presence of isothiazolinones via 2 methods: LITK and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). METHODS: No-ISO dish soaps (n = 9), a convenience sample of patient products (n = 6), and controls (positive [isothiazolinone declared], n = 5; negative, n = 2) were tested with LITK (X3) and UHPLC-MS/MS. RESULTS: Several no-ISO dish soaps and personal products were positive for isothiazolinones (LITK, n = 12; UHPLC-MS/MS, n = 3). Ultrahigh-performance liquid chromatography-tandem mass spectrometry specifically identified methylisothiazolinone alone in 1 no-ISO dish soap, methylchloroisothiazolinone in another, and both in a third. Using UHPLC-MS/MS as the criterion standard, we observed the accuracy of LITK for 9 dish soaps was poor (sensitivity, 66.7%; specificity, 20%) and very poor for 6 personal care products (sensitivity, 0%; specificity, 0%). CONCLUSIONS: Personal products may contain undeclared isothiazolinones. The current study found that LITK had poor accuracy for testing dish soap and personal care products. Clinicians should be aware of these factors when managing patients with contact allergy to isothiazolinones.

Isothiazolinone Content of US Consumer Adhesives: Ultrahigh-Performance Liquid Chromatographic Mass Spectrometry Analysis.

BACKGROUND: There are limited data regarding the prevalence and concentration of isothiazolinone preservatives in consumer adhesives. OBJECTIVES: The aim of this study was to determine the prevalence and concentration of 5 specific isothiazolinones (methylisothiazolinone [MI], methylchloroisothiazolinone [MCI], benzisothiazolinone [BIT], butyl BIT, and octylisothiazolinone) in US adhesives. METHODS: Thirty-eight consumer adhesives were analyzed using ultrahigh-performance liquid chromatographic-mass spectrometry. Fisher exact tests were used to test for isothiazolinone content and: 1) glue format (2) application purpose and 3) extraction method. RESULTS: Nineteen adhesives (50%) had at least 1 isothiazolinone, and 15 contained 2 isothiazolinones. Frequencies and concentrations were as follows: MI (44.7%; 4-133 ppm), MCI (31.6%; 7-27 ppm), BIT (15.8%; 10-86 ppm), and octylisothiazolinone (2.6%; 1 ppm). Butyl BIT was not detected in any of the adhesives. Format (stick vs liquid) was not statistically associated with isothiazolinone presence. At least half of adhesives in the following application purposes had at least 1 isothiazolinone: shoe, craft, fabric, and school. All-purpose glues had a statistically significant lower concentration of MI and MCI, whereas craft glues were associated with higher concentrations of MI and MCI. Compared with other glues, fabric adhesives were associated with a higher risk of containing BIT. CONCLUSIONS: Half of the tested adhesives contained at least 1 isothiazolinone. Methylisothiazolinone and MCI were the most common. Consumers and dermatologists should be aware of adhesives as a source of isothiazolinones.

Isothiazolinone in Residential Interior Wall Paint: A High-Performance Liquid Chromatographic-Mass Spectrometry Analysis.

BACKGROUND: There is limited information regarding isothiazolinone content in residential wall paints in the United States. OBJECTIVE: The aim of this study was to evaluate the prevalence of 5 isothiazolinones-methylisothiazolinone (MI), methylchloroisothiazolinone, benzisothiazolinone (BIT), butyl BIT, and octylisothiazolinone-in US residential wall paints. METHODS: Forty-seven paints were obtained from retailers in Minneapolis/St Paul, Minnesota. Paint samples were assessed for the presence of the 5 isothiazolinones using high-performance liquid chromatographic-mass spectrometry. RESULTS: At least 1 isothiazolinone was detected in all 47 paints. However, no paint contained butyl BIT, and only 1 paint had octylisothiazolinone. The MI and BIT were found in 96% and 94% of the paints, respectively. Methylisothiazolinone ranged in concentration from 17 to 358 ppm, whereas BIT varied from 29 to 1111 ppm. Methylchloroisothiazolinone was found solely in oil-based paints. Isothiazolinones were declared in 15% of Safety Data Sheets but did not correlate with high-performance liquid chromatographic-mass spectrometry. One "preservative-free" paint had BIT at 71.5 ppm. Paint sheen was not statistically associated with BIT or MI concentrations. Unpigmented paints and paints with volatile organic compound claims had significantly lower concentrations of MI, but not BIT. CONCLUSIONS: All paints contained at least 1 isothiazolinone. Methylisothiazolinone and BIT were the most common. Safety Data Sheets are insufficient for ascertaining isothiazolinone content in US paints.

In vitro dermal penetration of 4-chloro-3-methylphenol from commercial metal working fluid and aqueous vehicles.

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.

Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride.

The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to reversibly inhibit the activity of acetylcholinesterase. The inactivation of the enzyme was detected by monitoring the accumulation of yellow color produced from the reaction between thiocholine and dithiobisnitrobenzoate ion. The kinetic parameter, Km for the substrate (acetylthiocholine), was found to be 0.216 mM and Ki for MPTP inactivation of acetylcholinesterase was found to be 2.14 mM. The inactivation of enzyme by MPTP was found to be dose-dependent. It was found that MPTP is neither a substrate of AChE nor the time-dependent inactivator. The studies of reaction kinetics indicate the inactivation of AChE to be a linear mixed-type inhibition. The dilution assays indicate that MPTP is a reversible inhibitor for AChE. These data suggest that once MPTP enters the basal ganglia of the brain, it can inactivate the acetylcholinesterase enzyme and thereby increase the acetylcholine level in the basal ganglia of brain, leading to potential cell dysfunction. It appears that the nigrostriatal toxicity by MPTP leading to Parkinson's disease-like syndrome may, in part, be mediated via the acetylcholinesterase inactivation.

Effect of chlorogenic acid on hydroxyl radical.

Chlorogenic acid (CGA) is considered to act as an antioxidant. However, the inhibitory effects of CGA on specific radical species are not well understood. Electron spin resonance (ESR) in combination with spin trapping techniques was utilized to detect free radicals. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was used as a spin trapping reagent while the Fenton reaction was used as a source of hydroxyl radical (*OH). We found that CGA scavenges *OH in a dose-dependent manner. The kinetic parameters, IC50 and Vmax, for CGA scavenging of *OH were 110 and 1.27 microM/sec, respectively. The rate constant for the scavenging of *OH by CGA was 7.73 x 10(9) M(-1) sec(-1). Our studies suggest that the antioxidant properties of CGA may involve a direct scavenging effect of CGA on *OH.

Determination of alachlor and its metabolites in rat plasma and urine by liquid chromatography-electrospray ionization mass spectrometry.

A method based on liquid chromatography (LC) in combination with mass spectrometry (MS) for the analysis of alachlor (ALA) and its metabolites, 2-chloro-N-[2,6-diethylphenyl]acetamide (CDEPA) and 2,6-diethylaniline (DEA), in rat plasma and urine has been developed. 13C-labeled ALA was used as the internal standard for quantitation. The analyte in plasma or urine was isolated using a Waters Oasis HLB extraction plate. The mass spectrometer was operated in the ESI MS-SIM mode with a programming procedure. The retention times for ALA, CDEPA and DEA were 1.84, 3.11 and 4.12 min, respectively. The limits of quantification (LOQ) for ALA, CDEPA and DEA were 2.3, 0.8 and 0.8 ng per injection, respectively. The linear fit of analyte to mass response had an R2 of 0.99. Reproducibility of the sample handling and LC-MS analysis had a RSD of < or = 10%. The average recoveries for these analytes in rat plasma were better than 90%. Similar results were obtained with rat urine.