A critical review finds styrene lacks direct endocrine disruptor activity

The European Commission lists styrene (S) as an endocrine disruptor based primarily on reports of increased prolactin (PRL) levels in S-exposed workers. The US Environmental Protection Agency included S in its list of chemicals to be tested for endocrine activity. Therefore, the database of S for potential endocrine activity is assessed. In vitro and in vivo screening studies, as well as non-guideline and guideline investigations in experimental animals indicate that S is not associated with (anti)estrogenic, (anti)androgenic, or thyroid-modulating activity or with an endocrine activity that may be relevant for the environment. Studies in exposed workers have suggested elevated PRL levels that have been further examined in a series of human and animal investigations. While there is only one definitively known physiological function of PRL, namely stimulation of milk production, many normal stress situations may lead to elevations without any chemical exposure. Animal studies on various aspects of dopamine (DA), the PRL-regulating neurotransmitter, in the central nervous system did not give mechanistic explanations on how S may affect PRL levels. Overall, a neuroendocrine disruption of PRL regulation cannot be deduced from a large experimental database. The effects in workers could not consistently be reproduced in experimental animals and the findings in humans represented acute reversible effects clearly below clinical and pathological levels. Therefore, unspecific acute workplace-related stress is proposed as an alternative mode of action for elevated PRL levels in workers.