Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudyEmbryotoxicity and teratogenicity study with gamma-cyclodextrin in rabbits.
In a standard embryotoxicity/teratogenicity study, gamma-cyclodextrin (gamma-CD) was administered to groups of 16, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. A comparison group received a diet containing 20% lactose. Treatment started on day 0 of gestation and ended on day 29 when the animals were killed. ⋯ Uterine weight, placental weight, fetal weight, number of fetuses, sex ratio, number of implantation sites, resorptions, and corpora lutea did not differ among the groups. Visceral and skeletal examinations of the fetuses did not reveal any malformations, anomalies, or variations that could be attributed to treatment. It was concluded that dietary gamma-CD is well tolerated by pregnant rabbits, has no adverse effect on reproductive performance, and is not embryotoxic, fetotoxic, or teratogenic at dietary concentrations of up to 20%.
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Regul. Toxicol. Pharmacol. · Apr 1998
Subchronic (13-week) oral toxicity study of gamma-cyclodextrin in dogs.
The oral toxicity of gamma-cyclodextrin (gamma-CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received gamma-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs and no mortalities occurred. Transient diarrhea occurred in some dogs of the 5 and 10% dose groups and in all dogs of the 20% dose group. ⋯ These changes are well-known physiological responses to the presence of increased amounts of undigested, fermentable carbohydrates in the lower gut. At the high applied intakes an incomplete digestion of gamma-CD and/or a partial inhibition of pancreatic amylase by gamma-CD could account for these effects. It is concluded that daily gamma-CD consumption of up to 20% in the diet (approximately 7.7 g/kg body wt in male and 8.3 g/kg body wt in female dogs) was tolerated without any toxic effects.
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Regul. Toxicol. Pharmacol. · Apr 1998
Comparative StudySubchronic oral toxicity studies with gamma-cyclodextrin in rats.
The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of eight alpha-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered to groups of 5 male rats at dietary levels of 0, 5, 10, 15, and 20%. In the 13-week study, groups of 20 rats/sex received diets with 0, 1.5, 5, or 20% gamma-CD. ⋯ Except for a slight cecal enlargement, which is commonly observed in rodents upon ingestion of incompletely absorbed carbohydrates, organ weights did not exhibit relevant changes as a result of gamma-CD treatment. On histopathological examination (13-week study), no treatment-related abnormalities were found. In conclusion, the ingestion of gamma-CD for 13 weeks at dietary levels of up to 20% (corresponding to intakes of 11.4 and 12.7 g/kg body wt/day for male and female rats, respectively) was well tolerated and did not produce any signs of toxicity.
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Regul. Toxicol. Pharmacol. · Oct 1997
Review Comparative StudyHealth risk assessment of drinking water contaminants in Canada: the applicability of mixture risk assessment methods.
The objectives of this article are: (i) to review the current approaches of Health Canada to the risk assessment of drinking water contaminants, and (ii) to examine the applicability of mixture risk assessment methods to drinking water contaminants. Health Canada's current approaches to drinking water risk assessment, like those of many regulatory agencies, focus almost solely on the effects of individual chemicals. As such, no formal method is currently used for developing mixtures guidelines or for modifying guidelines of individual chemicals to account for the possibility of the occurrence of interactions (supraadditive or infraadditive). ⋯ Specifically, among the components-based approaches, dose-addition, response-addition, and the toxic equivalency factor approaches are the most applicable ones for drinking water contaminants. Until an interactions-based, mechanistic risk assessment approach (e.g., physiological model-based approach) becomes available for routine use, the components-based approaches remain the default methods for consideration. Progress in the development and validation of an interactions-based risk assessment methodology should facilitate a more realistic assessment of risk due to drinking water contaminants without increasing the levels of uncertainty in risk estimates above those associated with existing single-chemical methods.