{'fraction_non_alphanumeric': 0.026439232409381664, 'fraction_numerical': 0.006823027718550106, 'mean_word_length': 5.571428571428571, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Reducing pre-clinical blood volumes for toxicokinetics: toxicologists, pathologists and bioanalysts unite.

Blood samples are taken from animals during general toxicology, reproductive toxicology and safety pharmacology studies with pharmaceutical and non-pharmaceutical chemicals to demonstrate that the compound is present in the groups of animals being tested and to understand how the degree of systemic exposure may be linked to any toxicological effects observed. The blood (plasma or serum) concentration data generated from each sample are used to derive toxicokinetic (TK) data and regulatory guidance dictates generally how and when these data are needed during compound development. A number of OECD and ICH documents [1–6] indicate the value of relating achieved exposure to toxicological findings and how this provides useful information for estimating safety margins for clinical trials and for supporting dose level selection for chronic toxicity studies. For pharmaceuticals, typically, a full concentration profile is needed at the start and end of a study, but there is some variation between organizations in the number of samples taken to generate a profile and whether all or selected control animals are sampled [7]. For non-pharmaceutical chemicals, the use of TK in toxicology studies is not generally required in the registration processes but is considered beneficial [8–10]. There are differences across industry sectors in how TK data are generated and used, but the advantages of monitoring exposure in toxicity studies are frequently discussed and agreed [11,12]. From a risk assessment perspective for non-pharmaceutical chemicals, actual animal exposure to parent and metabolites may be used to unravel the relevance of toxicological findings to human health, regardless of how the TK profile is generated (e.g. steady state determinations in dietary studies versus PK-like profiling in oral gavage studies) [13]. Other uses include comparing ‘external’ and ‘systemic’ “no observed adverse effect levels” across studies, setting an internal reference dose or chemical-specific uncertainty factors, enabling the use of physiologically based pharmacokinetic modeling [11]. Exposure data are useful where different doses, species, strains, gender and life stages are compared at the end of a toxicology program [14].