Tolylfluanid permeates human skin slowly and as dimethylamino sulfotoluidid (DMST).

Tolylfluanid (TF) is a sensitizing biocide used in antifouling products and wood preservatives. Paint application is associated with skin exposure; however, the importance of this exposure route is uncertain as TF skin permeation rates are lacking in the peer-reviewed scientific literature. TF is a lipophilic powder that hydrolyses rapidly in contact with water to dimethylamino sulfotoluidid (DMST). DMST is also a TF metabolite. We characterized TF and DMST skin permeation using an ex vivo flow-through diffusion system with viable and frozen human skin. TF permeated as DMST with a low permeation rate (0.18 ± 0.05 μg/cm <sup>2</sup> /h) and a moderate time lag (7.1 ± 1.4 h) in viable human skin. Applying DMST gave a 3.5-fold lower permeation rate (0.05 ± 0.01 μg/cm <sup>2</sup> /h) compared to TF under a similar experimental setting. We simulated paint activities in an exposure chamber to understand a possible skin exposure from airborne TF concentrations. Although, paint can deposit onto the skin during work activities, TF permeation when paint was applied to human skin ex vivo was very low (as TF: 0.004 ± 0.005 μg/cm <sup>2</sup> /h, and as DMST: 0.02 ± 0.001 μg/cm <sup>2</sup> /h). Our results show that TF can permeate skin, and consequently, can contribute to sensitization, which support previous reports on sensitization in TF exposed workers

Influence of collection and storage materials on glycol ether concentrations in urine and blood.

Glycol ethers, such as propylene glycol monomethyl ether (PGME) and propylene glycol monobuthyl ether (PGBE) are solvents found in many professional and domestic products. In biomonitoring studies, the type of materials used to collect, store, and transport these samples can greatly influence the analytical results because materials can adsorb the analyte. Plastic tubes generally have a hydrophobic internal surface that can reduce the concentration of certain chemicals and result in an underestimation of workers' exposures. The aim of this study was to assess whether the storage of PGME and PGBE spiked blood and urine samples led to different PGME and PGBE concentrations in vials made of glass and common plastics (polypropylene (PP), polyethylene (PE) or polystyrene (PS)). Glycol ether concentrations were quantified with headspace gas chromatography equipped with a flame ionization detector. Our results show stable urinary PGME and PGBE concentrations in PP, while up to 15% variations in urinary PGME for PE and PS. For PGME and PGBE in blood, we observed no statistically significant losses in glass, while losses were recorded for all types of plastic tested (PS, PP and PE). We conclude that biomonitoring samples should be collected in glass for blood and PP for urine

Human skin permeation rates ex vivo following exposures to mixtures of glycol ethers.

Skin exposure to cleaning products in the general and occupational population are a public health concern. Among the most frequently identified amphiphilic organic solvents in cleaning products are propylene glycol monomethyl ether (PGME) and propylene glycol n-butyl ether (PGBE). Internal dose from skin exposure may be efficiently evaluated using in vitro flow-through diffusion cells with excised human skin. Our aim in this study was two-fold; 1) characterize the permeation rates (J), time lag (T <sub>lag</sub> ), and permeation coefficients (Kp) of PGME and PGBE in human ex-vivo skin permeation assays, and 2) determine a possible mixture effect on skin permeation characteristics when applied together. Our results showed a short T <sub>lag</sub> for PGME and was reduced further depending on the amount of PGBE in the mixture (T <sub>lag</sub> was reduced from 2 h to 1-1.7 h) for fresh skin. PGBE T <sub>lag</sub> slightly increased when mixed with 50 % or more PGME. Permeation rate decreased to half for both PGME and PGBE in mixture at any concentration. This substantial permeation was greater with previously frozen skin. This mixture effect could favor permeation of other compounds through human skin

Predicting human neurotoxicity of propylene glycol methyl ether (PGME) by implementing in vitro neurotoxicity results into toxicokinetic modelling

cells. However, we cannot exclude possible long-term neurodegenerative effects because inflammation was observed in vitro. Our simple TK model can be parameterized for other glycol ethers and used in parallel with in vitro data for systematically screening for neurotoxicity. If further developed, this approach could be adapted to predict brain neurotoxicity from exposure to organic solvents