RESUMEN
Implementation of reliable methodologies allowing Reduction, Refinement, and Replacement (3Rs) of animal testing is a process that takes several decades and is still not complete. Reliable methods are essential for regulatory hazard assessment of chemicals where differences in test protocol can influence the test outcomes and thus affect the confidence in the predictive value of the organisms used as an alternative for mammals. Although test guidelines are common for mammalian studies, they are scarce for non-vertebrate organisms that would allow for the 3Rs of animal testing. Here, we present a set of 30 reporting criteria as the basis for such a guideline for Developmental and Reproductive Toxicology (DART) testing in the nematode Caenorhabditis elegans. Small organisms like C. elegans are upcoming in new approach methodologies for hazard assessment; thus, reliable and robust test protocols are urgently needed. A literature assessment of the fulfilment of the reporting criteria demonstrates that although studies describe methodological details, essential information such as compound purity and lot/batch number or type of container is often not reported. The formulated set of reporting criteria for C. elegans testing can be used by (i) researchers to describe essential experimental details (ii) data scientists that aggregate information to assess data quality and include data in aggregated databases (iii) regulators to assess study data for inclusion in regulatory hazard assessment of chemicals.
RESUMEN
BACKGROUND: Studies on the effects of (-)-hydroxycitric acid (HCA) in humans are controversial. As differences in the HCA preparations may contribute to this apparent discrepancy, the aim of the current study is to compare different HCA-containing preparations in adult Wistar rats. DESIGN: The effects of 3 different HCA-containing preparations (Regulator, Citrin K, Super CitriMax HCA-600-SXS, all used at an effective HCA dose of 150 and 300 mg/kg, administered intragastrically) on food intake and body weight were studied in adult male Wistar rats. The efficacy was tested under 2 different experimental conditions: 1) after a single dose administration and 2) during repeated administration for 4 subsequent days. RESULTS: Regulator and Citrin K significantly reduced food intake in both experimental setups, while Super CitriMax HCA-600-SXS was less effective. When administered for 4 subsequent days Regulator and Citrin K diminished body weight gain. CONCLUSION: Regulator and Citrin K were shown to be potent inhibitors of food intake in rats, whereas Super CitriMax HCA-600-SXS showed only small and more inconsistent effects. The striking differences in efficacy between these 3 preparations indicate that low doses of a relatively low-effective HCA preparation may have contributed to the lack of efficacy as found in several human studies.