Regulatory toxicology and pharmacology : RTP
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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.
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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.
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Regul. Toxicol. Pharmacol. · Jun 2004
Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rats.
The embryotoxicity/teratogenicity of alpha-cyclodextrin (alpha-CD) was examined in Wistar Crl:(WI)WU BR rats. alpha-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The additions to the diet of alpha-CD and lactose were made at the expense of pregelatinized potato starch. ⋯ Maternal reproductive performance was not affected by the alpha-CD treatment. Examination of the fetuses for external, visceral and skeletal changes did not reveal any fetotoxic, embryotoxic, or teratogenic effects of alpha-CD. In conclusion, no adverse effects were observed at alpha-CD intakes of up to 20% of the diet, the highest dose level tested at which the rats consumed about 13 g/kg bw/day.
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Regul. Toxicol. Pharmacol. · Apr 2004
Health effect levels for risk assessment of childhood exposure to arsenic.
Health risks to children from chemicals in soil and consumer products have become a regulatory focus in the U. S. This study reviews short-term health effect levels for arsenic exposure in young children (i.e., 0-6 years old). ⋯ The available data collectively indicate a lowest-observed-adverse-effect level around 0.05mg/kg-day for both acute and subchronic exposure. At low doses, children do not appear to be more sensitive than adults on a dose-per-body-weight basis, although data for acute exposures are limited and uncertainties exist for quantifying potential neurological or vascular effects at low-level subchronic exposures. Based on these data, possible reference levels for acute and subchronic exposure in young children are 0.015 and 0.005mg/kg-day, respectively.