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Background: Endometriosis is one of the common causes of infertility with very diverse etiology. In modern lifestyle, humans are exposed to several endocrine-disrupting chemicals (EDCs) which may lead to reproductive disturbances. Diethyl hexyl phthalate (DEHP) is one of the common EDCs to which women are exposed by the use of cosmetics, perfumes, food packaging, medicine, and insecticides. Aim: The aim of this study was to measure the levels of DEHP in women diagnosed with endometriosis and healthy females and to compare these levels among different stages of endometriosis. Setting and Design: This descriptive study was conducted at a tertiary care hospital. Subjects and Methods: This study comprised of fifty women diagnosed with endometriosis, aged 20–40 years, and fifty age-matched healthy, fertile women without endometriosis. Females on any medication/comorbid conditions were excluded from the study. Serum DEHP concentrations were measured by high-performance liquid chromatography (HPLC). The results were expressed as means ± standard deviation (SD) (ng/ml of DEHP). Statistical Analysis: Data were analyzed using IBM-SPSS version 20. Two-sample Student's t-test and one-way ANOVA were applied for the analysis. Results: The mean ± SD value of DEHP in cases was 65.29 ± 21.69 ng/ml; however, the mean ± SD value of DEHP in controls was undetectable. Comparison of DEHP among stages of endometriosis revealed an increasing trend with advanced stages (III and IV). The values were not different between the two age groups of women with endometriosis (20–30 and 31–40 years). Conclusion: High levels of DEHP in women diagnosed with endometriosis suggest a role of phthalates in the etiology of endometriosis and permit careful use of such compounds.

Plastik ürünlerin ana bileşenlerinden olan DEHP ve BPA östrojenin etkilerini taklit ederek veya bozarak vücut üzerindeki etkilerini inhibe eden önemli endokrin bozuculardır. BPA ve DEHP'nin bu kadar yaygın kullanılmasından dolayı tek başlarına maruz kalma değil aynı zamanda kombine maruz kalma da önemli bir konu olarak kabul edilmektedir. Günümüzde endokrin bozucu etkilerinin yanı sıra nörolojik fonksiyonlar üzerindeki etkileri ile iligili araştırmalar da artmaktadır. Bu çalışmada BPA ve DEHP'ye kombine maruz kalmanın toksikolojik açıdan değerlendirilmesi ve karnozik asidin muhtemel koruyucu etkilerinin araştırılması amaçlanmıştır. Bu çalışmada, 16 haftalık (25 ila 35 g vücut ağırlığı) C-57BL / 6 fareleri BPA (16, 5, 1.6 mg/kg), DEHP (16, 5, 1.6 mg/kg), 20 mg/kg CA, BPA+DEHP (16, 5, 1.6 mg/kg) ve BPA+DEHP+20 mg/kg CA (16, 5, 1.6 mg/kg). olacak şekilde rasgetle 14 gruba (6 fare/grup) ayrılmıştır. Kimyasal maruziyet subakut toksisite açısından değerlendirilmiş ve 28 gün boyunca oral gavaj yoluyla ilaç uygulaması yapılmıştır. Son uygulamadan 24 saat sonra fareler dekapite edilmiştir. İlaç uygulamasına başlanmadan önce ve sonrasında davranış üzerindeki etkileri incelemek için farelere hızlandırılmış rotarod ve pasif sakınma testleri yapılmıştır. Ayrıca kortekste MDA seviyesi ile GSH-Px, CAT ve SOD aktiviteleri incelenmiştir. Daha sonra korteksteki Bcl-2, Bax, BACE ve p-tau seviyeleri western blot yöntemi ile tespit edilmiştir. Pasif sakınma ve rotarod testlerinde anlamlı bir sonuç elde edilememiştir. BPA+DEHP ve BPA+DEHP+20CA'nin bütün gruplarında SOD aktivitesi kontrol grubuna göre anlamlı olarak azalmıştır 5 ve 16 BPA+DEHP gruplarının CAT aktivitesi kontrole kıyasla anlamlı şekilde artarken, 1.6 ve 16 BPA+DEHP+20CA gruplarının CAT aktivitesi 16 BPA ve 1.6 DEHP gruplarına kıyasla anlamlı şekilde azalmıştır. BPA+DEHP ve BPA+DEHP+20CA'nin bütün gruplarının GSH-Px aktivitelerinde CAT aktivitesine benzer değişimler gözlemlenmiştir. Her ne kadar BPA ve DEHP gruplarında anlamlı bir değişim olmamasına rağmen, BPA+DEHP beraber verildiği gruplarda MDA seviyeleri kontrole karşı anlamlı bir şekilde azalmıştır. BPA+DEHP kombine verildiği grupların Bcl-2 ve Bax seviyeleri anlamlı şekilde artarken; karnozik asidin BPA+DEHP kombinasyon gruplarına eklenmesi BPA+DEHP gruplarına kıyasla anlamlı bir azalmaya sebep olmuştur. Her ne kadar BPA+DEHP kombine veridiği grupların BACE enzim ekspresyon seviyesi anlamlı ölçüde artarken BPA+DEHP+20CA kombine veridiği grupların BACE enzim ekspresyon seviyesi anlamlı şekilde azalmıştır. Fakat doz-cevap arasında ters etki vardır. Ayrıca çalışamalarımızda kaspaz-3, APP ve amiloid beta (1-42) testlerinde herhangi bir ilişki görülmemiştir. BPA + DEHP gruplarının p-tau düzeyleri diğer gruplardan anlamlı derecede düşük olmakla birlikte, BPA + DEHP + 20CA gruplarının p-tau seviyeleri, BPA + DEHP gruplarına kyasla anlamlı olarak artmıştır. Sonuç olarak, BPA ve DEHP beraber verildiği zaman, kortekste oluşan nörodeneretif hasarın oksidatif stress kaynaklı olduğu ve karnozik asidin radikal süpürücü özelliği ile koruma sağladığı görülmüştür. DEHP and BPA, the main components of plastic products, are the important endocrine-disrupting chemicals which can mimic or disrupt the actions of estrogen by inhibiting normal functions of the body. Because of this widespread usage of DEHP and BPA, not only alone exposure but also combined exposure is considered as an important issue. Nowadays, researches are increased related to the effects on neurological functions instead of endocrine disrupting effects. This study aims to investigate combined exposure of DEHP and BPA and the possible protective effect of carnosic acid as an antioxidant. In this study, C-57BL/6 mice aged 16 weeks (25 g to 35 g of body weight) were randomly divided into 15 groups (6 mice/group) as BPA (16, 5, 1.6 mg/kg), DEHP (16, 5, 1.6 mg/kg), 20 mg/kg CA, BPA+DEHP (16, 5, 1.6 mg/kg) and BPA+DEHP+20 mg/kg CA (16, 5, 1.6 mg/kg). Chemical exposure was assessed for subacute toxicity and application was made for 28 days by oral gavage. The animals were sacrificed 24 h after the last administration. Before and after drug administration passive avoidance and accelerated rotarod tests were conducted to examine the effects on behavior. And also, level of MDA, GSH-Px, CAT and SOD activities in the cortex were analyzed. Then Bcl-2, Bax, BACE and p-tau levels in the cortex were detected by western blot. There was not observed any change in passive avoidance and rotarod tests. The SOD activity of all dosage of BPA+DEHP and BPA+DEHP+20CA significantly decreased according to control. In CAT activity, while combined administration of 5 and 16 BPA+DEHP significantly increased as compared with control, combined administration of 1.6 and 16 BPA+DEHP+20CA significantly decreased as compared with 16 BPA and 1.6 DEHP. The same changes were observed in GSH-Px activity levels of BPA+DEHP+20CA and BPA+DEHP groups like CAT activity. Although there were no significant changes observed in BPA and DEHP groups, combined administration of BPA+DEHP caused a significant decrease in MDA levels according to control. While Bcl-2 and Bax levels were significantly increased at combined administration of BPA+DEHP, addition of CA to BPA+DEHP combination caused significantly decrease as compared to BPA+DEHP administration. Although the level of BACE enzyme expression significantly increased in combined administration of BPA+DEHP, BACE levels were significantly decreased in the combined administration of BPA+DEHP+20CA. However, there was an opposite effect between dose and response. And also, in our studies, no relevance was observed in the caspase-3, APP and amyloid beta tests. While p-tau levels of BPA+DEHP groups were significantly lower than other groups, p-tau levels of BPA+DEHP+20CA groups significantly increased compared to combined administration of BPA+DEHP groups. In conclusion, when BPA and DEHP used together, they damaged the cortex in terms of neurodegeneration by oxidative stress and also carnosic acid has been shown protection by radical scavenging properties. 117

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.