Acetaminophen affects the survivor, pigmentation and development of craniofacial structures in zebrafish (Danio rerio) embryos

In spite of its toxic effects, N-acetyl-p-aminophenol (APAP), also commonly known as acetaminophen or paracetamol, is one of the most widely used analgesic and antipyretic agents. It can be obtained without a medical prescription. To test the effect over the zebrafish embryonic development, a Fish Embryo acute Toxicity (FET) test was carried out with acetaminophen to establish the range of concentrations that cause a harmful effect on the zebrafish development. Diminished pigmentation (in embryos treated from 0 h post-fertilization) and blockage of melanin synthesis (in larvae treated from 72 h post-fertilization) were detected, suggesting the involvement of this compound in the development of black pigment cells as described recently for human epidermal melanocytes. Morphological abnormalities such as aberrant craniofacial structures, pericardial edemas, and blood accumulation were also found. All these effects could be due to higher levels of apoptotic cells detected in treated embryos. Therefore, teratogenic effects of acetaminophen cannot be ruled out, and its wide use should be taken with caution.