Institution: | 1. Aqaba International Laboratories/BENHAYYAN, ASEZA, Aqaba 77110, Jordan;2. Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands;3. Philadelphia University, Faculty of Pharmacy, P.O. Box 1, Amman 19392, Jordan;4. Department of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands |
Abstract: | The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1′-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7–15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10?5 mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000–385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable. |