Evidence suggesting that di-n-butyl phthalate has anti-androgenic effects in fish

This article is the pre-print version of the full and final published article.Phthalate ester plasticizers are anti-androgenic in mammals. High doses of certain phthalates consistently interfere with the normal development of male offspring exposed in utero, causing disrupted sperm production, abnormal development of the genitalia, and in some cases infertility. In the environment, phthalates are considered ubiquitous and are commonly measured in aquatic ecosystems at low ng to mu g per litre concentrations. Given the similarity between mammalian and teleost endocrine systems, phthalate esters may be able to cause anti-androgenic endocrine disruption in fish in the wild. In the present study, adult male three-spined sticklebacks (Gasterosteus aculetaus) (n = 8) were exposed to di-n-butyl phthalate (DBP) (0, 15, and 35 mu g DBP/L) for 22 d and analyzed for changes in nesting behavior, plasma androgen concentrations, spiggin concentrations, and steroidogenic gene expression. Plasma testosterone concentrations were significantly higher in males from the 35 mu g DBP/L group compared with the solvent control, whereas plasma 11-ketotestosterone concentrations were not significantly affected. Expression of steroid acute regulatory protein and 3 beta-hydroxysteroid dehydrogenase remained unchanged. Spiggin concentrations were significantly lower in the males exposed to 35 mu g DBP/L. Nest building appeared to be slower in some males exposed to DBP, but this was not statistically significant. These results suggest that DBP has anti-androgenic effects in fish. However, further research is required to firmly establish the consequences of chronic DBP exposure in fish

Phthalate ester toxicity in human cell cultures

Di-2-ethylhexyl phthalate and butyl glycolyl butyl phthalate, plasticizers which can be leached into blood from polyvinyl chloride-containing medical devices, cause significant growth inhibition in cultures of the human diploid cell strain WI-38. The ID50 (dose which causes 50% growth inhibition in tissue culture) values for di-2-ethylhexyl phthalate and butyl glycolyl butyl phthalate were 70 [mu] and 12 [mu], respectively, for WI-38 cells. Toxic effects were greater in a replicating cell population than in a nonreplicating, confluent cell layer. WI-38 cells which were grown in 160 [mu] di-2-ethylhexyl phthalate for 3 days, and subsequently subcultured into control medium, showed only 60% of control growth after 5 days in control medium. Cells treated with 14 [mu] butyl glycolyl butyl phthalate for 3 or 5 days exhibited growth equivalent to the controls when subcultured into control medium. Toxic levels for di-2-ethylhexyl phthalate were within the range of concentrations found in blood which has been stored in polyvinyl chloride blood bags for up to 21 days at 4[deg]C. ID50 values were reported for several other phthalate esters and for two nonphthalide compounds which are leachable from certain polyvinyl chloride plastic medical devices.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22136/1/0000565.pd

The Endocrine Disruptor Mono-(2-Ethylhexyl) Phthalate Affects the Differentiation of Human Liposarcoma Cells (SW 872)

Esters of phthalic acid (phthalates) are largely used in industrial plastics, medical devices, and pharmaceutical formulations. They are easily released from plastics into the environment and can be found in measurable levels in human fluids. Phthalates are agonists for peroxisome proliferator-activated receptors (PPARs), through which they regulate translocator protein (TSPO; 18 kDa) transcription in a tissue-specific manner. TSPO is a drug- and cholesterol-binding protein involved in mitochondrial respiration, steroid formation, and cell proliferation. TSPO has been shown to increase during differentiation and decrease during maturation in mouse adipocytes. The purpose of this study was to establish the effect of mono-(2-ethylhexyl) phthalate (MEHP) on the differentiation of human SW 872 preadipocyte cells, and examine the role of TSPO in the process. After 4 days of treatment with 10 µM MEHP, we observed changes in the transcription of acetyl-CoA carboxylase alpha, adenosine triphosphate citrate lyase, glucose transporters 1 and 4, and the S100 calcium binding protein B, all of which are markers of preadipocyte differentiation. These observed gene expression changes coincided with a decrease in cellular proliferation without affecting cellular triglyceride content. Taken together, these data suggest that MEHP exerts a differentiating effect on human preadipocytes. Interestingly, MEHP was able to temporarily increase TSPO mRNA levels through the PPAR-α and β/δ pathways. These results suggest that TSPO can be considered an important player in the differentiation process itself, or alternatively a factor whose presence is essential for adipocyte development