Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Dec 2010
Investigation of endogenous soybean food allergens by using a 2-dimensional gel electrophoresis approach.
As part of the safety assessment of genetically modified (GM) soybean, 2-dimensional gel electrophoresis analyses were performed with the isoxaflutole and glyphosate tolerant soybean FG72, its non-GM near-isogenic counterpart (Jack) and three commercial non-GM soybean lines. The objective was to compare the known endogenous human food allergens in seeds in the five different soybean lines in order to evaluate any potential unintended effect(s) of the genetic modification. In total, 37 protein spots representing five well known soybean food allergen groups were quantified in each genotype. ⋯ Overall, there was no significant increase in the level of allergens in FG72 soybean seeds. Therefore, the FG72 soybean can be considered as safe as its non-GM counterpart with regards to endogenous allergenicity. Additional research is needed to evaluate the biological variability in the levels of endogenous soybean allergens and the correlation between level of allergens and allergenic potential in order to improve the interpretation of these data in the safety assessment of GM soybean context.
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Regul. Toxicol. Pharmacol. · Nov 2010
Proposal of new uncertainty factor application to derive tolerable daily intake.
We propose new uncertainty factors (UFs) and a new subdivision of default factors in chemical risk assessment using a probabilistic approach based on the latest applicable information. Rounded values of 150 for mice, 100 for hamsters and rats, and 40 for rabbits, monkeys and dogs for inter- and intra-species differences (UF(AH)) were derived from the probabilistic combination of two log-normal distributions. Further calculation of additional UFs when chronic data (UF(S)) or NOAEL (UF(L)) are lacking was conducted using available log-normal distribution information. ⋯ The default contributions of inter-species difference (UF(A)) and intra-species difference (UF(H)) to the UF(AH) of 100 for hamsters and rats as an example are considered to be 25 and 4, respectively. The UF(A) of 25 was subdivided into 25(0.6) (i.e., 7.0) for pharmacokinetics (PK) (UF(A,PK)) and 25(0.4) (i.e., 3.6) for pharmacodynamics (PD) (UF(A,PD)), and the UF(H) of 4 was evenly subdivided into 4(0.5) (i.e., 2) (UF(H,PK) and UF(H,PD)), to account for chemical-specific difference data between humans and laboratory animals for PK and/or PD. These default UFs, which come from actual experimental data, may be more appropriate than previous default UFs to derive tolerable daily intake values.
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Regul. Toxicol. Pharmacol. · Nov 2010
Comparative StudyToxicity study of a new camptothecin anti-cancer agent CKD-602 in dogs: 4-week continuous intravenous dose by infusion pump and 4-week repeated intravenous dose.
In evaluating toxicity, one of the most important factors is the administration method, because it can affect the exposure and absorbance level of the test article, and, consequently, influence the interpretation of toxicity test results. Continuous intravenous (IV) administration is a widely used administration method for anti-cancer drugs in clinical settings. Previous studies have reported the toxic effects of the test article following repeated IV dosing of CKD-602, a novel camptothecin-derivative anti-tumor agent that was developed by Chong Kun Dang Pharmaceutical Corporation in Seoul, Korea. ⋯ Higher mortality, more severe clinical symptoms, increased complete blood count, serum biochemistry, and histopathology were demonstrated when CKD-602 was administered using the 4-week continuous IV infusion pump method compared with the repeated IV administration method. Based on these results, we conclude that the administration of CKD-602 using the 4-week continuous IV infusion pump method can elicit more severe toxicity than that using 4-week repeated IV dosing method. Thus, more attention should be paid to the administration of CKD-602 using continuous IV infusion in the clinical setting.
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Regul. Toxicol. Pharmacol. · Oct 2010
Comparison of potential risks of lactic acidosis induction by biguanides in rats.
Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. ⋯ In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level.
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Regul. Toxicol. Pharmacol. · Jul 2010
Randomized Controlled TrialAcute effects of cigarette smoking on pulmonary function.
Chronic smoking related changes in pulmonary function are reflected as accelerated decrease in FEV1 although histologic changes occur in the peripheral bronchi earlier. More sensitive pulmonary function parameters might mirror those early changes and might show a dose response. ⋯ The data indicate acute and reversible effects of cigarette smoke exposures and no-smoking on mid to small size pulmonary airways in a dose dependent manner.