Use of the benchmark dose approach for evaluation of dose and time-dependent response to 7-hydroxycoumarin 90-day exposure in rat females
Journal Title: Український журнал сучасних проблем токсикології - Year 2018, Vol 81, Issue 1
Abstract
Benchmark dose (BMD) analysis of existing data sets from experimental studies on animal for which NOAEL/LOAEL information is available allows to satisfy the need for quantifiable, scientifically justifiable approach to risk assessment. Previous study of 7-hydroxycoumarin (7-HOC) 3 months toxicity on rats revealed carbohydrates and lipids metabolism disturbance (blood glucose level (BGL) decrease, serum triglyceride level (STL) rise) as biologically relevant parameters to set up NOEL (20 mg/kg). Purpose. To conduct the dose and time of exposure effect dependence comparative analysis of BGL and STL published data set of 7-HOC subchronic toxicity in rats using BMD and NOAEL/LOAEL methodologies. Materials and methods. The available continuous data of STL and BGL from subchronic 7-HOC toxicity study data set for rat females were analyzed by means United States Environmental Protection Agency proposed software, BMDS 2.6.0.1. The response level was set as 10 %. Results. Hill’s model appropriately reflected BGL and STL dependence on 7-HOC dose. The BMDs estimates of STL rise were similar (46–49 mg/kg) in 1, 2, and 3 months of exposure. Coincident dependence was foundfor the lower-bound confidence limits on the BMDs (BMDLs) ranged 21–22 mg/kg at all the studied time points, whereas NOEL for this end point was defined as 50, 20, and 20 mg/kg in 1, 2, and 3 months respectively. BMDs of the BGL decrease were rising with time of exposure amounting 48, 93, 486 mg/kg after 1, 2, and 3 months respectively. BMDLs estimates were 24, 21, 207 mg/kg in 1, 2, and 3 months respectively, while NOEL for this end point were 50, 200, and 200 mg/kg at correspond time points. Conclusion. The benchmark dose method was more powerful statistical tool to analyze 7-HOC effects dose dependence in comparison to traditional approach. The observed BMDs and theirs derivatives changes indicated no enhancement of studied treatment related responses within the exposure time.
Authors and Affiliations
M. L. Zinovieva, P. G. Zhminko, M. G. Prodanchuk
Keywords
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