Toxic effects of phthalates on in vitro cellular models: A systematic review and meta-analysis (2014–2024)

Abstract

Phthalic acid esters are plasticizers that enhance malleability, flexibility, and durability. Studies show that phthalates have been found in the tissues and fluids of organisms, including humans, raising health concerns. This systematic review summarizes studies on the effects of these compounds in various cell types. Using PRISMA criteria, a search was conducted in the CAPES Journals Portal database, from the past decade, employing the descriptors "phthalate," "in vitro," and "cytotoxicity." Out of the initial 128 results, 37 articles met the inclusion criteria and were categorized by physiological systems. These articles were classified as events (n = 41), exceeding the total number of articles as follows: female reproductive (n = 12), musculoskeletal (n = 7), digestive (n = 4), male reproductive (n = 4), respiratory (n = 3), integumentary (n = 3), circulatory and cardiovascular (n = 2), urinary (n = 2), nervous (n = 2), hematopoietic (n = 1), and immune (n = 1). The results highlight the predominance of di(2-ethylhexyl) phthalate (DEHP) in the studies, followed by dibutyl phthalate (DBP) and di-isononyl phthalate (DINP). Besides, studies highlight the considerable risks of phthalates to human health, mainly regarding the endocrine disruption and reproductive toxicity. This review recommends long-term exposure studies of phthalate mixtures and mechanistic explorations in human-relevant cell models. Furthermore, studies exploring establish concentrations and different phthalates are necessaries to understand profoundly the effect on health.