The most pronounced effects (highest S-value) are then used to translate results into four categories which are defined as follows: Q ⩽ 0.8 or S 0–5: slightly irritating, Q > 0.8 to <1.2 or S 6–12: moderately irritating, Q ⩾ 1.2 to < 2.0 or S 13–15: irritating, Q ⩾ 2 or S 16–18: severely irritating (R41 or GHS Cat 1) (see Table 3). For the purpose of assessing test items for classification purposes, the categories “slightly irritating” and “moderately irritating” were combined into one single category termed “not irritating”, since both are analogous to non-classified results from in vivo tests. Tests were performed according p38 MAP Kinase pathway to GLP. Of the 20 products included in this study, three were alkaline (pH ⩾11.5; effectively between 12.7 and 13) and 17 acidic (pH ⩽2; effectively between 0.5 and 2.0) (see Table 1). Besides the extreme pH, selection criteria were the relevance of the products with regard to the market and risk management implications of the product use. In addition, nine individual compounds were tested in parallel in aqueous dilution (see Table 2) of which three selleck chemical were alkaline and four acidic in the extreme pH range. Two of the compounds, a solvent and a detergent,
do not have an extreme pH. The selection followed several criteria: (a) a frequent use in industrial products, (b) the concentration should be at the lower limit for classification (as irritating) according to DSD and (c) the concentration should also be in a realistic range that is often used in products. Based on provisions in chemicals legislation, we have implemented
a testing and assessment Selleckchem Paclitaxel scheme for industrial products with extreme pH values. The principle of weight of evidence is employed at each step of data generation/collection. Without any further information, a product with an extreme pH value should be considered as corrosive, unless further (converse) evidence is available. If there is an interest to further assess the irritating/corrosive properties, data generation usually starts with the determination of the alkali/acid reserve. Exonerative results from this method are then further verified or falsified by in vitro experiments. The first in vitro test is the human skin model test for corrosivity. Again, exonerative results require further investigation which is done by the human skin model test for skin irritation and the HET-CAM for eye irritation. Information gained by these experiments is always weighed by expert judgment in the overall context, taking into account the knowledge on the properties of the product ingredients, CCM and AR results and in vitro data. Details of the testing and assessment scheme are shown in Fig. 1. Testing would of course not be needed in cases where overriding data is available for a product, like human experience or animal data, or if bridging principles based on similar products that have already been tested are applicable.