The purpose of the present investigation is to analyze the in vivo genotoxicity doseresponse data of ethylene oxide (EO) and the applicability of the derived point-ofdeparture (PoD) values when estimating permitted daily exposure (PDE) values. A total of 40 data sets were identified from the literature, and benchmark dose analyses were

Male B6C3F1 mice were administered styrene monomer by oral gavage for 29 consecutive days at dose levels of 0, 75, 150, or 300 mg/kg/day. The highest dose level represented the maximum tolerated dose based on findings in a 28‐day dose range‐finding study, in which the bioavailability of orally administered styrene was also confirmed. The positive control group received ethyl nitrosourea (ENU; 51.7 mg/kg/day) on Study Days 1–3 and ethyl methanesulfonate (EMS; 150 mg/kg/day) on Study Days 27–29 by oral gavage. Approximately 3 h following the final dose, blood was collected to assess erythrocyte Pig‐a mutant and micronucleus frequencies. DNA strand breakage was assessed in glandular stomach, duodenum, kidney, liver, and lung tissues using the alkaline comet assay. The %tail DNA for stomach, liver, lung, and kidney in the comet assay among the styrene‐treated groups was neither significantly different from the respective vehicle controls nor was there any dose‐related increasing trend in any of the tissues; results for duodenum were interpreted to be inconclusive because of technical issues. The Pig‐a and micronucleus frequencies among styrene‐treated groups also did not show significant increases relative to the vehicle controls and there was also no evidence for a dose‐related increasing trend. Thus, orally administered styrene did not induce DNA damage, mutagenesis, or clastogenesis/aneugenesis in these Organization of Economic Co‐operation and Development test guideline‐compliant genotoxicity studies. Data from these studies can contribute to the overall assessment of genotoxic hazard and risk posed to humans potentially exposed to styrene.

Highly inbred strains of mice have contrasting means and low ranges for the trait of gonosomal univalency at diakinesis-metaphase I. Randomly bred and mixed strains have wider ranges. The inbred strain DBA/2J has a high mean, and this character is evidently transmitted through the male parent. This material may provide a valuable model for study of genetic control of XY pairing.

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