Acute mixture toxicity of halogenated chemicals and their next generation counterparts on zebrafish embryos.

Perfluorinated chemicals and flame retardants are halogenated compounds commonly used in food packaging and in clothing and electronics, respectively. Due to the hazardous effects of many of these chemicals, manufacturers are developing next generation potential less toxic alternatives. The objective of this study was to assess the toxicity of potentially "safer" alternatives, singly and in mixtures, in relation to their first generation counterparts. We used zebrafish embryos as our model organism due to its high structural and functional homology to other vertebrates and its suitability for early developmental studies. We tested three well studied halogens, perfluorooctanoic acid (PFOA), tris (1,3-dichloro-2-propyl) phosphate (TDCPP) and tetrabromobisphenal A (TBBPA), and two less-studied next generation chemicals, 9,10-Dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) and perfluorobutyric acid (PFBA). First, we identified their lethal concentration (LC50) under 96 h exposures using zebrafish embryos; chemical LC50 values ranged from 1.3 to 13,795 ppm. Next, we tested the toxicity of tertiary mixtures containing the estimated LC50 values for each chemical which ranged from 126 to 5,094 ppm. We found that chemicals within these mixtures displayed concentration addition suggesting a similar mode of toxic action. Importantly, next generation chemicals were less acutely toxic singly and in mixtures than their first generation counterpart.