Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?

Round 1

Reviewer 1 Report

This review focus on the impact of phthalates on female rodents behaviour. The review is well structure and written. The remaining questions is what it is know about the impact seen in rodents when translates to humans.

Author Response

We added the following paragraph at the end of the “Discussion” section” to present briefly what is known in humans about phthalate exposure and how could be the data obtained in rodents translated in humans:

“In humans, epidemiological studies reported associations between exposure to phthalates and low interest in sexual activity in women (Barrett et al. 2014). Previous systematic reviews of the literature also support an association between prenatal exposure to phthalates and adverse cognitive outcomes and neurological disorders (Ejaredar et al., 2015; Hlisnikova et al., 2021). Other studies described an association between urinary phthalates and anxiety or depressive symptoms in young adults (Xu et al., 2020) or elderly population (Kim et al., 2016). It is possible that these effects in humans occur through disruption of endocrine systems including those related to sex steroids. Indeed, it is largely known that sex steroids are not only mandatory for sexual function but they also influence anxiety state level and cognition (Borrow and Handa, 2017; Hsu et al., 2021; Szoeke et al., 2021). Therefore, the adverse effects and mode(s) of action reported in rodents following environmental exposure to phthalates might be also relevant for humans.”

Reviewer 2 Report

The authors reviewed studies on reproductive toxicity of phthalates and their derivatives in men and women. A preliminary discussion on its sensitivity to female individuals was also conducted. The authors mainly review the effects of phthalates and their derivatives on reproductive and mood-related behaviors, learning, and memory in female individuals, and further review the effects of phthalate exposure on brain development and neuroplasticity , which in turn influenced behavioral changes in animals. The authors also reviewed the exposure concentrations of phthalates and their derivatives and their respective effects on individuals of different developmental ages. The authors' review of the effects of phthalates and their derivatives on female reproductive behavior is detailed, comprehensive and coherent; it has a positive impact on assessing the risks of phthalates to human health.

Author Response

We would like to thank you for your constructive and positive feedback.

The text was edited for English before the first submission by a professional native English editor of our institution.