Recovery from developmental nonylphenol exposure is possible for female rats

• Developmental exposure to nonylphenol resulted in a life-long impact on the exposed individual.
• Nonylphenol caused endocrine and metabolic disruption in F1, and F2 rats.
• The F3 rats showed characteristics similar to vehicle-treated control rats.
• Recovery from nonylphenol toxicity is possible if further exposure is prevented.

Nonylphenol (NP) is an environmental endocrine-disrupting chemical that has been detected in human cord blood and milk. Developmental exposure to NP is unavoidable and can lead to hyperadrenalism, a syndrome that resembles Cushing’s disease and has a life-long impact on the affected individual. In this study, we investigated the recovery of female rats from developmental exposure to NP and the effects of such exposure on future generations. Female rats were time-mated, and rats in the experimental group (NP group) were administered NP in drinking water (2 μg/mL) throughout gestation and lactation. Pregnant females in the control group were given water only (Veh group). The resulting litters were recognized as the first-generation F1 offspring. The F1 females were time-mated with non-sibling F1 males within the same treatment group. NP was not administered after the F0 generation. The treatment procedures for F3 offspring were identical to those for the F2 generation. The experimental results showed that the observed characteristics of the F3 NP generation had reverted to normal and resembled those of the F3 Veh generation. Thus, our study indicated that developmental exposure to NP resulted in a life-long impact on the exposed individual, but that recovery to the “normal” state was possible if further NP exposure was prevented.