Oral Toxicity of Bis(2-Ethylhexyl) Phthalate During Pregnancy and Suckling in the Long–Evans Rat

Arcadi, Francesca Antonia; Costa, Chiara; Imperatore, C.; Marchese, Anna; Rapisarda, Antonio; Salemi, Monica; Trimarchi, Giuseppe; Costa, Giovanni

doi:10.1016/s0278-6915(98)00065-9

Cited by 210 publications

(95 citation statements)

References 29 publications

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“…Like DEHP, DBP is also a testicular toxicant and causes reproductive tract malformations in male rats after in utero exposure (Arcadi et al 1998;Gray et al 1999;Moore et al 2001;Mylchreest et al 1998Mylchreest et al , 1999Parks et al 2000). Among the structurally related phthalates, DEHP, DBP, DPP, and DHP cause testicular atrophy and are both female and male reproductive toxicants in rodents (Heindel and Powell 1992).…”

Section: Reproductive and Developmental Toxicity In Animal Modelsmentioning

confidence: 99%

Mechanisms of phthalate ester toxicity in the female reproductive system.

Lovekamp-Swan

Davis

2003

Environ Health Perspect

573

288

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Phthalates are high-production-volume synthetic chemicals with ubiquitous human exposures because of their use in plastics and other common consumer products. Recent epidemiologic evidence suggests that women have a unique exposure profile to phthalates, which raises concern about the potential health hazards posed by such exposures. Research in our laboratory examines how phthalates interact with the female reproductive system in animal models to provide insights into the potential health effects of these chemicals in women. Here we review our work and the work of others studying these mechanisms and propose a model for the ovarian action of di-(2-ethylhexyl) phthalate (DEHP). In vivo, DEHP (2 g/kg) causes decreased serum estradiol levels, prolonged estrous cycles, and no ovulations in adult, cycling rats. In vitro, monoethylhexyl phthalate (MEHP; the active metabolite of DEHP) decreases granulosa cell aromatase RNA message and protein levels in a dose-dependent manner. MEHP is unique among the phthalates in its suppression of aromatase and in its ability to activate peroxisome proliferator-activated receptors (PPARs). We hypothesize that MEHP activates the PPARs to suppress aromatase in the granulosa cell. MEHP-, PPAR alpha-, and PPAR gamma-specific ligands all similarly decreased estradiol production and RNA message levels of aromatase in vitro. Our model shows that MEHP acts on the granulosa cell by decreasing cAMP stimulated by follicle stimulating hormone and by activating the PPARs, which leads to decreased aromatase transcription. Thus, the environmental contaminant DEHP, through its metabolite MEHP, acts through a receptor-mediated signaling pathway to suppress estradiol production in the ovary, leading to anovulation.

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Section: Reproductive and Developmental Toxicity In Animal Modelsmentioning

confidence: 99%

Mechanisms of phthalate ester toxicity in the female reproductive system.

Lovekamp-Swan

Davis

2003

Environ Health Perspect

573

288

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“…Young rats are more susceptible than older rats (Sjö berg et al 1986;Poon et al 1997) and perinatal exposure to 325 ml DEHP/l drinking water for 42 days results in disorganisation of seminiferous tubules and detachment of the spermatogonial cells (Arcadi et al 1998). It has been reported that the active DEHP-metabolite MEHP specifically disrupt the FSHinduced cyclic AMP synthesis in cultured rat adult Sertoli cells (Grasso et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Toxicity Study of Di(2‐Ethylhexyl)phthalate (DEHP) in Combination with Acetone in Rats

Dalgaard¹,

Østergaard

Lam

et al. 2000

Pharmacology & Toxicology

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Abstract:In two separate studies with exposure duration 9 weeks or 4 weeks, male Wistar rats were dosed with di(2-ethylhexyl)phthalate (DEHP) by gavage and exposed to drinking water with or without acetone (0.5% wt/v in the 9-week study, 1.0% wt/v in the 4-week study). In the 9-week study the doses of DEHP were 0, 125, 250, 500 or 1000 mg/kg b.wt. In the 4-week study the doses of DEHP were increased to 1000, 5000 and 10,000 mg/kg b.wt. In the 9-week study, the relative liver weight was increased in the rats exposed to 500 and 1000 mg/kg b.wt. No interaction of DEHP and acetone was observed in any of the measured parameters. In the 4-week study DEHP, at the highest dose level, resulted in severe general toxicity. The group exposed to DEHP in combination with acetone was more affected. Male fertility was decreased. Body weight was decreased, and the relative weight of the liver, kidney, heart, brain and adrenals increased. The relative weight of the testes decreased in the 5000 and 10,000 mg/kg b.wt. groups. The weight of seminal vesicles and epididymals decreased at 10,000 mg/kg b.wt. In animals exposed to 5000 and 10,000 mg DEHP/kg b.wt. a severe atrophy of the seminiferous tubules and a slight diffuse Leydig's cell hyperplasia was observed. The cellular debris and conglomerates of desquamated cells found in the lumen of the seminiferous tubules were immunostained positive for vimentin. This indicates that Sertoli cell cytoplasm is included in the conglomerates -an interesting finding not previously described. No specific interaction of DEHP and acetone was observed in any of the measured parameters.It is well known that di(2-ethylhexyl)phthalate (DEHP) induces testicular atrophy in rats (Woodward 1988). Low doses of the monoester derivative mono(2-ethylhexyl)-phthalate (MEHP) have been shown to induce the same effect as the diester, and MEHP is considered the most potent metabolite of DEHP (Teirlynck et al. 1988). The role of other metabolites, e.g. 2-ethylhexanol is not fully elucidated. Both the phthalic acid and the aliphatic (ethylhexyl) part of DEHP may be toxic to the testis. The possible contribution of the aliphatic part to the testis toxicity can be examined by administering acetone concomitantly with DEHP. If enhancement of testis toxicity occurs, this may be interpreted as an indication of ethylhexyl contribution to toxicity. A small fraction of 2-ethylhexanol may be metabolised to a g-diketone, and it is well known that acetone potentiates the toxicity of g-diketones (Misumi & Nagano 1985). We have previously reported on the interaction between acetone and 2,5-hexanedione, the testis toxic metabolite of n-hexane (Larsen et al. 1991). The present study was performed to investigate a possible enhancement of the toxicity of DEHP by acetone in testis and the peripheral nervous system. Several Sertoli cell toxicants i.e. acrylamide, carbon disulfide, 2,5-hexanedione and tri-o-cresyl phosphate induce testis toxicity and peripheral neuropathy, possibly by affecting the cytoskeleton (Boekelheide 1993 the ne...

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“…Since they are physically bound to the polymer chains, PEs may be released into the environment during the production, use, or incineration of polymeric materials containing them (1,2). Due to the potential risks of PEs to human health and the environment (3,4), several of them have been included in the list of priority pollutants by different national and international organizations. For example, the United States (US) Environmental Protection Agency (EPA) has established a maximum admissible concentration (MAC) of 6 µgL −1 for di-ethylhexyl phthalate (DEHP) in water (5).…”

Section: Introductionmentioning

confidence: 99%

Investigation of Di-ethylhexyl Phthalate Migration by Applying Magnetic Solid Phase Extraction Method Followed by GC-FID Determination

Faraji¹,

Adeli

2016

Nutr Food Sci Res

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A B S T R A C T Background and Objectives:The addition of plasticizers (mainly phthalates and adipates) makes plastic flexible and popular for packaging, storing and preserving food, water, and so on. The most widely used plasticizer in food contact applications is di-ethylhexyl phthalate (DEHP) though being suspected to have carcinogenic and estrogenic properties. The aim of this study is application of magnetic solid phase extraction as new absorbent for determination of DEHP in water samples by gas chromatography (GC). Materials and Methods:Important factors in extraction, separation and determination processes were optimized using the one-variable-at-a-time method. For optimization, all tests were performed two times.Figures of merit of the proposed method were evaluated. The amount of DEHP in some water samples was determined using the proposed method. Results:The results showed that the obtained chromatogram of extract was free of significant interference. The preservatives' recoveries ranged from 91.6% to 102.2%. Limit of detection and limit of quantitation were 0.1 mg kg -1 and 0.3 µg L -1 , respectively. Concentration of DEHP in the studied samples was in the range of N.D-2.3 µg L -1 . Conclusions:The acceptable performance and reliability of the proposed method were demonstrated. Temperature and time were fount as the most effective parameters in migration of DEHP.

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Oral Toxicity of Bis(2-Ethylhexyl) Phthalate During Pregnancy and Suckling in the Long–Evans Rat

Cited by 210 publications

References 29 publications

Mechanisms of phthalate ester toxicity in the female reproductive system.

Mechanisms of phthalate ester toxicity in the female reproductive system.

Toxicity Study of Di(2‐Ethylhexyl)phthalate (DEHP) in Combination with Acetone in Rats

Investigation of Di-ethylhexyl Phthalate Migration by Applying Magnetic Solid Phase Extraction Method Followed by GC-FID Determination

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