The combined effects of preservative chemicals in consumer products: an analysis using embryonic and adult zebrafish.

Benzisothiazolinone (BIT) and propyl paraben (PP) are preservatives in cleaning products; however, their toxicities are not well understood. In this study, zebrafish embryos were exposed to BIT, PP, and mixtures of both for 96 h to investigate the effects on growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the transcription of 19 genes related to the GH/IGFs axis. Concentrations of BIT and PP were measured in the whole body of larvae. Zebrafish pairs were also exposed to BIT, PP, and mixtures for 21 d to evaluate the effects on sex hormones, histology in gonad, and transcription of 22 genes related to the hypothalamus-pituitary-gonad axis and vitellogenin. The mixtures had potentiation effects on development, reproduction, hormones, and gene transcripts than individual exposure. Larvae exposed to 229 μg L-1 BIT, 64.5 μg L-1 PP, and mixtures showed reduced growth. Decreased GH and IGF-1 levels were supported by gene regulation associated with the GH/IGFs axis. In larvae, reactive oxygen species, superoxide dismutase, catalase, and glutathione peroxidase levels were increased under all exposures. The gonadosomatic index in males and number of eggs decreased after mixture exposure. In females exposed to mixtures, the percentage of atretic follicle in ovary was significantly increased. The significant decrease in testosterone in males and significant decrease in 17β-estradiol in females exposed to mixtures suggest anti-estrogenic and anti-androgenic potential. Thus, preservative mixtures in consumer products may be more toxic than the individual substances, which is important for managing the risks of mixing preservatives.