Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways

• DOI: 10.1021/acs.est.3c05026
• Publication Date: 2023-08-29T12:14:45Z
• Authors: Haoqi Nina Zhao; Sydney P. Thomas; Mark J. Zylka; Pieter C. Dorrestein; Wenxin Hu
• Keywords: Retinoid X receptor; Developmental toxicity

The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg or investigate urine excretion transfer. Female male exhibited sex difference profiles 6PPDQ. Urine concentrations were one order magnitude lower than those 6PPD, suggesting higher bioaccumulation In from embryonic day 11.5 15.5, showed ∼1.5–8 times placenta, embryo body, brain, Using vitro dual-luciferase reporter assays, revealed that activated human retinoic acid receptor α (RARα) retinoid X (RXRα) at as low 0.3 μM, which was ∼10-fold detected urines. RXRα 1.2 μM. These results demonstrate exposure risks during pregnancy emphasize need for further toxicological epidemiological investigations.