ABSTRACT
The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays.
Subject(s)
Animal Testing Alternatives , Teratogens/toxicity , Toxicity Tests/methods , Animals , Aromatase/metabolism , Biological Assay , Cell Line , Cells, Cultured , Embryo, Nonmammalian/drug effects , Embryonic Stem Cells/drug effects , Humans , Mice , Rats , Receptors, Steroid/metabolism , Reproducibility of Results , Reproduction , Steroid 17-alpha-Hydroxylase/metabolism , ZebrafishABSTRACT
BACKGROUND: Psychotic symptoms have been linked to religious experience, but empirical evidence is scarce. We have investigated the impact of the Welsh religious revival (RR) of 1904-1905 on the number of admissions to the regional psychiatric hospital, their diagnostic features and lifelong course. METHOD: All case-notes of patients admitted to the North Wales Hospital between 1902 and 1907 were included. RESULTS: There was a significant increase in admissions for brief polymorphic psychoses (BPP; ICD-10: F23.0 and F23.1) in the revival years, but the number of first admissions for other mental disorders did not change. The vast majority of BPP admissions were linked to a revival meeting and did not result in further admissions. CONCLUSIONS: Intensive religious experience can lead to transient psychotic episodes. Our data also support the view that BPP triggered by life events rarely lead to chronic mental illness, distinguishing them from other psychoses and supporting the validity of the concept of reactive psychosis.
