Dermal irritancy assessment of microbial toxins and pesticidal contaminants found in recreational water using two- and three-dimensional human skin models

Dermal exposure to freshwaters contaminated with pesticides and microbial toxins may result in toxicity. This study assessed the in vitro dermal irritancy of selected pesticides and microbial toxins using two- (2D) and three-dimensional (3D) human skin models. The 2D model was normal human keratinocytes. The 3D model was EpiDerm, derived from normal human keratinocytes that forms a multi-layered differentiated human epidermal model. Pesticides included dimethipin, α-1,2,3,4,5,6-hexachlorocylohexane, oxyfluorfen, permethrin, profenofos, and tribufos. Toxins included cylindrospermopsin and microcystin-LA, -LR, and -RR. Exposure to contaminants was either 1 or 24 h. Viability was assessed by the MTT assay. Results were determined relative to negative control. Significant effects in viability were observed in both models and time points. The greatest significant decrease in viability in the 2D model was tribufos at 1 h (23%) and cylindrospermopsin (37%) at 24 h. In the 3D model, the greatest significant decrease was microcystin-LA (16%) at 1 h and microcystin-RR (32%) at 24 h. Several microbial toxins and pesticides were cytotoxic in both models and time points. However, no contaminant tested in the 3D model for 1 h was > 50% cytotoxic, which would categorize a chemical as a dermal irritant (Organisation for Economic Cooperation and Development Test Guideline 439 for skin irritation). The 24 h exposure time point had a greater number of cytotoxic contaminants in both models, particularly the 2D model. Screening potential irritants in the 2D model for 24 h may prioritize chemicals for further assessment in the 3D model.