Toxicological and cytogenetic assessment of a Salacia oblonga extract in a rat subchronic study.

Salacia oblonga holds potential as a natural method to mitigate the blood glucose response for people with diabetes by inhibiting the activity of intestinal alpha-glucosidases. As part of a safety evaluation of novel ingredients for use in blood glucose control, the toxicity of a S. oblonga root extract (SOE) was evaluated in a subchronic 90-day feeding study in rats. An in vivo-in vitro rat peripheral blood lymphocyte chromosomal aberrations assay was added at termination of the subchronic rat study to examine cultured lymphocytes for possible chromosomal aberration induction. This was conducted due to a previous weak; although reproducible, positive chromosomal aberrations response in cultured peripheral blood human lymphocytes after acute in vitro treatment with SOE. The present study results indicate that SOE was negative for the induction of chromosomal aberrations in cultured rat peripheral blood lymphocytes after 90 consecutive days of treatment with SOE. The no observable adverse effect level (NOAEL) was determined to be 2,500 mg/kg/day following daily subchronic oral gavage administrations to rats.

A developmental safety study in rats using DHA- and ARA-rich single-cell oils.

The long-chain omega-3 and omega-6 fatty acids, docosahexaenoic and arachidonic acids, are important in fetal development, but may be depleted from the mother during pregnancy as she transfers reserves to the developing fetus in utero and later to the infant through her breast milk. Pregnant women can increase their dietary intake of these nutrients to maintain adequate maternal reserves and ensure an optimal infant supply. DHASCO(R) and ARASCO(R) oils, concentrated sources of docosahexaenoic and arachidonic acids, respectively, have been tested in acute and subchronic studies without toxic effects. The present developmental toxicity study was undertaken to test for potential teratogenic activity of these oils to ensure their safe use during pregnancy. DHASCO and ARASCO oils were administered by oral gavage to pregnant rats at doses up to 1250 and 2500 mg/kg body weight/day, respectively, during the period of organogenesis. Caesarean sections and necropsies were performed on day 20 of gestation. Maternal reproductive outcomes were analyzed, and fetal external, soft and skeletal tissue were examined. Treatment with these oils did not produce overt maternal toxicity, nor did either oil result in changes in pre- or postimplantation losses, resorptions, live births or sex ratios. Neither oil caused fetal malformations. Increased frequencies of renal variations in development occurred in a non-dose-dependent manner and were not toxicologically significant. We conclude that these oils are not teratogenic at doses that represent a 100-fold safety factor over expected use levels.

An acute oral gavage study of 3beta-acetoxyandrost- 5-ene-7,17-dione (7-oxo-DHEA-acetate) in rats.

The present study was done to assess the tolerance of rats for 3-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate, 7-ODA) when administered as a single oral gavage dose. Five groups of Sprague-Dawley rats (Crl:CD (SD) BR VAF/Plus) (five/sex/group) were treated with 7-ODA at a dose level of 0 (control), 250, 500, 1000, or 2,000 mg/kg of body weight in a dose volume of 10 ml/kg. Food and water were provided ad libitum. All animals survived in good health to the scheduled sacrifice on Day 15. The single oral administration of 7-ODA had no apparent effects on body weight. Food consumption was significantly higher for all female treated groups during week two; however, the statistically significant differences were not considered to be of clinical consequence. Treatment caused no apparent changes of gross or microscopic anatomical structures of nine different organs. This study demonstrated that the no-observable adverse effect level for a single oral dose of 7-ODA in male and female rats was 2,000 mg/kg.

An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7, 17-dione (7-oxo-DHEA-acetate) in rhesus monkeys.

To test the effects of 7-oxo-dehydroepiandrosterone-3 acetate (hereafter 7-ODA) in Rhesus macaques the steroid was administered by oral gavage to two male and two female monkeys. Dose levels of 250, 500, and 1,000 mg/kg body weight (BW)/day were administered on days 1, 3, and 5 respectively, and 1,000 mg/kg on days 7 through 11. Each group received the dose in a volume of 10 ml/kg BW. All animals survived to the scheduled sacrifice on day 12. No adverse clinical effects of 7-ODA were observed at the 250 or 500 mg/kg doses. Females vomited on non-treatment days and all animals vomited on some days after being given the 1000 mg/kg dose. Excessive salivation was observed before or immediately after dosing on days 9 through 11. Appearance, behavior and body weights were not altered by the treatments. Visual examination of all body cavities, and macroscopic and microscopic examination of 42 different organs and tissues found no lesions or abnormalities.

Sucrose acetate isobutyrate (SAIB): three-generation reproduction study in the rat and teratology studies in the rat and rabbit.

A three-generation reproduction study of sucrose acetate isobutyrate (SAIB) in Fischer 344 rats and teratology studies in Fischer 344 rats and New Zealand white rabbits were performed. Dietary SAIB concentrations to provide dose levels of 0, 0.5, 1.0 and 2.0 g/kg body weight were used for the rat studies, and 0, 0.5, 0.85 and 1.2 g/kg body weight doses of SAIB in corn oil were administered by gavage in the rabbit studies. F0 generation male rats were fed SAIB for 10 wk, and female rats were fed SAIB for 2 wk prior to mating. F1 generation rats were raised on the test diets to maturity, mated to produce F2a litters, and remated to produce the F2b litters that were examined for teratology. F2a rats were mated to study fertility indices for the F3 pregnancy. A decrease in female fertility compared with controls was noted at the highest dose of SAIB during breeding of the F1 generation to produce the F2a litters. No difference in fertility rate between controls and treated animals was noted in the results of the other three matings that were performed, and it was concluded that the reduction in female fertility was not related to SAIB treatment. No morphological abnormalities of soft tissue or skeleton were observed in the rat or rabbit teratology studies. The highest dose levels administered, 2.0 g SAIB/kg body weight in the rat and 1.2 g SAIB/kg body weight in the rabbit, were considered to be no-observed-adverse effect levels (NOAEL).

Terminology of developmental abnormalities in common laboratory mammals (version 1).

This paper presents the first version of an internationally-developed glossary of terms for structural developmental abnormalities in common laboratory animals. The glossary is put forward by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology, and represents considerable progress toward harmonization of terminology in this area. The purpose of this effort is to provide a common vocabulary that will reduce confusion and ambiguity in the description of developmental effects, particularly in submissions to regulatory agencies worldwide. The glossary contains a primary term or phrase, a definition of the abnormality, and notes, where appropriate. Selected synonyms or related terms, which reflect a similar or closely related concept, are noted. Nonpreferred terms are indicated where their usage may be incorrect. Modifying terms used repeatedly in the glossary (e.g., absent, branched) are listed and defined separately, instead of repeating their definitions for each observation. Syndrome names are generally excluded from the glossary, but are listed separately in an appendix. The glossary is organized into broad sections for external, visceral, and skeletal observations, then subdivided into regions, structures, or organs in a general overall head to tail sequence. Numbering is sequential, and not in any regional or hierarchical order. Uses and misuses of the glossary are discussed. Comments, questions, suggestions, and additions from practitioners in the field of developmental toxicology are welcomed on the organization of the glossary as well as on the specific terms and definitions. Updates of the glossary are planned based on the comments received.