Regulatory toxicology and pharmacology : RTP
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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.
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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.
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summary“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)
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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.
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Regul. Toxicol. Pharmacol. · Jun 2004
Allometric principles for interspecies extrapolation in toxicological risk assessment--empirical investigations.
Four types of data (toxicokinetic data of pharmaceuticals from six species including humans, LD(50) values from eight animal species, long-term NOAEL values of pesticides from mice, rats, and dogs, and toxicity data on anti-neoplastic agents from six species including humans) were used for interspecies comparisons. Species differences with regard to kinetic parameters and toxicity were evaluated and the concordance with predictions by allometric scaling according to caloric demand (allometric exponent 0.75) or to body weight (allometric exponent 1) was checked. For LD(50) values, agreement was poor for both allometric concepts. ⋯ The other three datasets are clearly in agreement with the allometric scaling according to caloric demand. Caloric demand scaling is thus proposed as a generic interspecies extrapolation method in the absence of substance-specific data. Moreover, the evaluated data make it possible to describe uncertainty associated with the process of interspecies extrapolation by allometric rules.