Exploration of the GARD™skin applicability domain: Indirectly acting haptens, hydrophobic substances and UVCBs.

Hazard assessments of skin sensitizers are increasingly performed using new approach methodologies (NAMs), with several in chemico, in vitro, and most recently, also defined approaches accepted for regulatory use. However, keeping track of potential limitations of each method to define applicability domains remains a crucial component to ensure adequate predictivity and to facilitate the appropriate selection of method(s) for each hazard assessment task. The objective of this report is to share test results generated with the GARD™skin assay on chemicals that have traditionally been considered difficult to test in some of the conventional in vitro and in chemico OECD Test Guidelines for skin sensitization.

The effect of a selective CXCR2 antagonist (AZD5069) on human blood neutrophil count and innate immune functions.

Aims: The aim of the present study was to investigate whether selective antagonism of the cysteine-X-cysteine chemokine receptor-2 (CXCR2) receptor has any adverse effects on the key innate effector functions of human neutrophils for defence against microbial pathogens.

Methods: In a double-blind, crossover study, 30 healthy volunteers were randomized to treatment with the CXCR2 antagonist AZD5069 (100 mg) or placebo, twice daily orally for 6 days. The peripheral blood neutrophil count was assessed at baseline, daily during treatment and in response to exercise challenge and subcutaneous injection of granulocyte-colony stimulating factor (G-CSF).

Recent developments in the risk assessment of potentially genotoxic impurities in pharmaceutical drug substances.

Controlling the quality of medicines is just as important as demonstrating efficacy. The International Conference on Harmonisation has published general guidance on the quality and safety assessment of impurities in pharmaceutical drug substances and drug products. More recently, the European Medicines Evaluation Agency has published a guideline focusing on limits for genotoxic impurities.

A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity.

The synthesis of pharmaceutical products frequently involves the use of reactive reagents and the formation of intermediates and by-products. Low levels of some of these may be present in the final drug substance and drug product as impurities. Such chemically reactive impurities may have at the same time the potential for unwanted toxicities including genotoxicity and carcinogenicity and hence can have an impact on product risk assessment.