Regulatory Toxicology and Pharmacology

This information is provided to augment the tables and figures in the manuscript and to provide additional information about methods used in this study.

Microsoft Excel workbook. "List" sheet includes all FDA reviews of New Drug Applications included in analysis linked to individual sheets for each review as well as the number of single dose acute toxicity, local tolerance and skin sensitization studies reported. "Summary" summarizes information captured in individual sheets and contains most of the information used in preparation of the manuscript. "Multiples" lists all FDA reviews in which more than one of any study type was reported indicating how the studies differed.

mean expression levels and standard deviations for herbicide sprayed and unsprayed GE breeding stacks

The file include the number of Individual case safety reports for ICSRs contained in the World Health Organization (WHO) global database of individual case safety reports (VigiBase) in which the following MedDRA preferred terms (PTs): “Cataract”, “Cataract cortical”, “Cataract nuclear” and “Cataract subcapsular” were reported for HMG-CoA reductase inhibitors according to the anatomical therapeutic chemical classification (ATC: C10AA) between inception on Nov 14, 1967, and Jan 15, 2019. Fixed-dose combinations of statins with other drugs were not considered. We also searched for ICSRs for the PTs mentioned above and prednisolone as a positive control – a drug previously known to cause cataract- and paracetamol/acetaminophen which served as a negative control -a drug not likely to be related with the occurrence of cataracts. Furthermore, we searched ICSRs of cataracts related to other lipid-lowering drugs classes different from statins: fibrates (ATC: C10AB), ezetimibe (ATC: C10AX09) and proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies (ATC C10AX13, C10AX14). Disproportional reporting was investigated through the calculation of the Reporting Odds Ratio with their 95% Confidence Interval using Woolf’s method. Subgroup analysis of the ROR of statins as a drug class were performed by sex and by age groups (more or less than 65 years old).

Tanimoto coefficients for the data set analysed

Supporting Information for 'A defined approach for predicting skin sensitisation hazard and potency based on the guided integration of in silico, in chemico and in vitro data using exclusion criteria'