Exposure to the synthetic phenolic antioxidant 4,4'-thiobis(6-t-butyl-m-cresol) disrupts early development in the frog Silurana tropicalis. 2022

Yol Monica Reyes, and Stacey A Robinson, and Amila O De Silva, and Cassandra Brinovcar, and Vance L Trudeau
Department of Biology, University of Ottawa, 30 Marie-Curie Private, Ottawa, ON K1N 9B4, Canada. Electronic address: yreye078@uottawa.ca.

Many chemicals in commonly used household and industrial products are being released into the environment, yet their toxicity is poorly understood. The synthetic phenolic antioxidant, 4,4'-thiobis(6-t-butyl-m-cresol) (CAS 96-69-5; TBBC) is present in many common products made of rubber and plastic. Yet, this phenolic antioxidant has not been tested for potential toxicity and developmental disruption in amphibians, a sensitive and susceptible class. We investigated whether acute and chronic exposure to TBBC would interfere with thyroid hormone-dependent developmental processes in the frog Silurana tropicalis and thus affect its early life-stage development. We exposed S. tropicalis embryos at the Nieuwkoop-Faber (NF) 9-10 stage to TBBC at nominal concentrations (0, 25, 50, 75, 100, 200 and 400 μg/L) to determine the 96h lethal concentrations and sublethal effects. We conducted a chronic exposure starting at stage NF47-48 to three sublethal TBBC nominal concentrations (0, 0.002, 0.1 and 5 μg/L) for 48-52 days to evaluate effects on growth and metamorphosis. The 96h lethal and effective (malformations) TBBC concentrations (LC50 and EC50) were 70.5 and 76.5 μg/L, respectively. Acute exposure to all TBBC concentrations affected S. tropicalis growth and was lethal at 200 and 400 μg/L. Chronic exposure to sublethal TBBC concentrations reduced body size by 8% at 5 μg/L and body mass by 17% at 0.002 μg/L when metamorphosis was completed. This study demonstrates that TBBC is toxic, induces malformations and inhibits tadpole growth after acute and chronic exposures. These findings call for further investigations on the mode of actions of TBBC and related antioxidants for developmental disruption in amphibians.

UI MeSH Term Description Entries
D007814 Larva Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. Maggots,Tadpoles,Larvae,Maggot,Tadpole
D008675 Metamorphosis, Biological Profound physical changes during maturation of living organisms from the immature forms to the adult forms, such as from TADPOLES to frogs; caterpillars to BUTTERFLIES. Biological Metamorphosis,Biological Metamorphoses,Metamorphoses, Biological
D003408 Cresols Any of three isomeric crystalline aromatic methylphenols, also known as hydroxytoluenes.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D001001 Anura An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae. Bombina,Frogs and Toads,Salientia,Toad, Fire-Bellied,Toads and Frogs,Anuras,Fire-Bellied Toad,Fire-Bellied Toads,Salientias,Toad, Fire Bellied,Toads, Fire-Bellied

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