Categorization of Chemicals According to Their Relative Human Skin Sensitizing Potency

Abstract

Although adoption of skin sensitization in vivo assays for hazard identification is likely to be successful in the next few years, this does not replace their use in potency prediction. Notably, measurement of potency of skin sensitizers in the local lymph node assay has been important. However, this local lymph node assay potency measure has not been formally assessed against a range of substances of known human sensitizing potential, because the latter is lacking. Accordingly, criteria for human data have been established that characterize 6 categories of human sensitizing potency, with 1 the most potent and 5 the least potent; category 6 represents true nonsensitizers. The literature has been searched, and 131 chemicals assigned into these categories according to their intrinsic potency judged only by the available human information. The criteria and data set generated provide a basis for examination of the capacity of nonanimal approaches for the determination of human sensitization potency.

Integrated testing strategies (ITS) for safety assessment

“…This was possible because many chemicals are well characterized with regard to their sensitization properties. In future this can be even further expanded by considering the corresponding human response (Basketter et al, 2014). While highlighting the importance of defining a set of reference substances for ITS development, this fact also highlights the difficulties in compiling a proper list of reference substances for other endpoints, such as reproductive toxicity, (developmental)neurotoxicity (Smirnova et al, 2014) and so on, when only in vivo animal data are available.…”

Improvement of human cell line activation test (h-CLAT) using short-time exposure methods for prevention of false-negative results

“…Therefore, LP medium exposure may be unsuitable for evaluating pro-haptens correctly. HCA was classified as a weaker skin sensitizer than predicted by LLNA (Basketter et al, 2014). It possesses a low capacity to induce skin sensitization under consumer-exposure conditions (Basketter et al, 2015).…”

“…Comparisons of the predictive performance of the h-CLAT alone and of this tiered system with that of LLNA using a previous data set (Ashikaga et al, 2010;Nukada et al, 2011;Takenouchi et al, 2013) are sum- marized in Tables 2 and 3. However, methylchloroisothiazolinone/methylisothiazolinone, NiSO 4 , and dextran (whose LogK ow values could not be calculated by KOW-WIN) and tocopherol (for which false positive results in LLNA have been reported [Basketter et al, 2014]), were excluded. Notably, this tiered system provided a sensitivity of 95% (overall chemicals) or 93% (chemicals with a LogK ow > 2.0) and an accuracy of 88% (overall chemicals) or 81% (chemicals with a LogK ow >2.0).…”

An economic approach to non-animal toxicity testing for skin sensitisation

“…The non-animal testing methods include the DPRA (Gerberick et al, 2007), the OECD profiler toolbox v3.2 (denoted hereinafter as "OECD Toolbox"; (OECD, 2012d)), the ARE-Nrf2 luciferase method covered by KeratinoSens TM (Emter et al, 2010) and LuSens (Ramirez et al, 2014), and the h-CLAT (Sakaguchi et al, 2006). The predictive capacities of all the non-animal testing methods and the LLNA were evaluated on human data (subset B in (Urbisch et al, 2015a), derived mainly from (Basketter et al, 2014)), using a sample of 114 substances (Table 3.4). In the skin sensitisation AOP, the DPRA captures the first key event (protein binding), KeratinoSens TM and LuSens the second key event (epithelial responses), and the h-CLAT captures the third key event (dendritic cell activation; (OECD, 2012a)).…”

“…The VOI is calculated for a set of individual non-animal testing methods, including in vitro, in silico and in chemico methods, seven battery combinations, 62 two-test and 174 three test sequential combinations of these non-animal testing methods (Urbisch et al, 2015a). Their VOIs are compared to the VOI of the local lymph node assay (LLNA) as the animal test (Mehling et al, 2012;Basketter et al, 2014;Urbisch et al, 2015a).…”