Developmental toxicity testing of unsubstituted and methylated 4- and 5-ring polycyclic aromatic hydrocarbons using the zebrafish embryotoxicity test

The present study evaluates the in vitro developmental toxicity of 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs) including benz[a]anthracene (BaA) and benzo[a]pyrene (BaP) and six of their monomethylated congeners, and dibenz[a,h]anthracene (DB[a,h]A) using the zebrafish embryotoxicity test (ZET). In general, the tested PAHs induced various developmental effects in the zebrafish embryos including unhatched embryos, no movement and circulation, yolk sac and pericardial edemas, deformed body shape, and cumulative mortality at 96 h post fertilization (hpf). The methyl substituent on different positions of the aromatic ring of the PAHs appeared to change their in vitro developmental toxicity. Comparison to a previously reported molecular docking study showed that the methyl substituents may affect the interaction of the PAHs with the aryl hydrocarbon receptor (AhR) which is known to play a role in the developmental toxicity of some PAHs. Taken together, our results show that methylation can either increase or decrease the developmental toxicity of PAHs, and suggest this may in part relate to effects on the molecular dimensions and resulting consequences for interactions with the AhR.