Regulatory toxicology and pharmacology : RTP
-
Regul. Toxicol. Pharmacol. · Aug 2004
Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats.
The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to be pregnant in the control, low-, mid-, and high-dose group, respectively. ⋯ Examination of the fetuses for external, visceral, and skeletal changes did not reveal any fetotoxic, embryotoxic or teratogenic effects of NHDC. In conclusion, no adverse effects were observed at NHDC levels of up to 5% of the diet, the highest dose level tested, at which the rats consumed about 3.3g/kg body weight/day. The observed cecal enlargement is a well-known physiological, adaptive response to the ingestion of high doses of a low-digestible substance and is generally accepted to lack toxicological relevance.
-
Regul. Toxicol. Pharmacol. · Aug 2004
Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats.
Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium acetate complex (HMRlignan; potassium acetate level approximately 20% w/w within the preparation) for days 0-21 of gestation. Test substance intake was calculated to be 0.14-0.18, 0.46-0.74, and 1.19-2.93 g/kg body weight/day for the low, mid, and high-dose groups, respectively. ⋯ Body weights of the remaining animals of the high-dose group were decreased. Food consumption was decreased in all treatment groups during the first three days of the gestation period as a result of decreased palatability of the feed. In conclusion, the no-observed-effect level (NOEL) for maternal effects was 1%, whereas the NOEL for fetal development following daily oral HMRlignan administration throughout the gestation was equivalent to 4% in the diet.
-
Regul. Toxicol. Pharmacol. · Jun 2004
Disposition of 14C-alpha-cyclodextrin in germ-free and conventional rats.
The absorption, disposition, metabolism, and excretion of uniformly (14)C-labeled alpha-cyclodextrin ((14)C-alpha-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, (14)C-alpha-CD (25 microCi, 50 mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, (14)C-alpha-CD (25 microCi, 200 mg/kg bw) was given by gavage to four male and four female germ-free rats. ⋯ No (14)C-alpha-CD was found in the feces. It is concluded from the data that ingested (14)C-alpha-CD is not digested in the small intestine of rats but is fermented completely by the intestinal microbiota to absorbable short-chain fatty acids. Therefore, the metabolism of alpha-CD resembles closely that of resistant starch or other fermentable dietary fibers.
-
“Cyclodextrin is frequently used in foods and cosmetics because it can change the physical properties of various compounds by their encapsulation within the cyclic structure. The average person is thought to ingest about 4 g of gamma-cyclodextrin per day from food. ... even people who have never received sugammadex may be sensitised by food and cosmetics.” (Mertes 2019)
-
Regul. Toxicol. Pharmacol. · Jun 2004
Subchronic (13-week) oral toxicity study of alpha-cyclodextrin in dogs.
The oral toxicity of alpha-cyclodextrin (alpha-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received alpha-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4 dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no mortalities occurred. Diarrhea occurred in all alpha-CD groups. ⋯ These changes are well-known physiological responses to the presence of high amounts of not digested, fermentable carbohydrates in the lower gut. They are known to be reversible on cessation of the treatment and are not associated with histological alterations of the intestinal tissues. It is concluded, therefore, that the high dose level, at which the male and female dogs consumed about 9.8 and 10.4 g alpha-CD/kg bw/d, respectively, is the NOAEL of this 13-week toxicity study.