Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells

Gray, Tim J.B.; Beamand, J.A.

doi:10.1016/0278-6915(84)90092-9

Cited by 219 publications

(112 citation statements)

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“…Although DEHP and DINP are produced in the largest quantities, these reference range data indicate a substantial internal human dose of DBP, DEP, and BzBP. MBP and MBzP are of particular concern because of their developmental and reproductive toxicity in animals (12)(13)(14)(15). Therefore, assessments of health risk from exposures to phthalates should include exposures to DBP, DEP, and BzBP.…”

Section: Resultsmentioning

confidence: 99%

“…Several phthalates, DEHP, dibutyl phthalate (DBP), and benzyl butyl phthalate (BzBP), are teratogenic in animals (8-10). DBP is also toxic to the testes, possibly through its metabolite, monobutyl phthalate (MBP) (11,12); other phthalate metabolites, monobenzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), are Sertoli cell toxicants and teratogens in animals (13,14). Furthermore, administration of DBP and DEHP to pregnant rats interferes with normal fetal development in male offspring (15).…”

mentioning

confidence: 99%

“…Furthermore, administration of DBP and DEHP to pregnant rats interferes with normal fetal development in male offspring (15). Regarding reproductive and developmental effects, phthalates vary in potency, with DEHP being the most potent and DBP and BzBP roughly an order of magnitude less potent (8)(9)(10)(11)(12)(13)(14)(15).Based on the varied toxicities of phthalates, internal dose measurements of specific phthalates and their monoester metabolites (16) are important for exposure assessment, and ultimately for accurate human risk assessment. Previous methods for assessing human exposure to phthalates have been subject to laboratory and sample-collection contamination problems from these environmentally ubiquitous compounds (17)(18)(19)(20).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population

Blount¹,

Silva²,

Caudill³

et al. 2000

Environmental Health Perspectives

115

147

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Dialkyl or alkyl aryl esters of 1,2-benzenedicarboxylic acid, commonly called phthalates, are ubiquitous industrial chemicals with a wide range of chemical and toxicologic characteristics. Phthalates are used primarily as plasticizers in flexible polyvinyl chloride (PVC) products such as blood bags and children's toys. Nonpolymeric uses of phthalates as fixatives, detergents, lubricating oils, and solvents lead to their inclusion in numerous and diverse products such as cosmetics and wood finishes. The widespread use of phthalates results in multiple human exposure routes (oral, dermal, inhalation, and intravenous). Phthalates are lipophilic compounds that appear not to bioaccumulate (1). Phthalates are rapidly metabolized to their respective monoesters and further oxidative products, which are glucuronidated and excreted through the urine and feces (1-4).Animal toxicology of several phthalates has been studied. Di-(2-ethylhexyl) phthalate (DEHP) is a rodent liver carcinogen through a mechanism thought to involve peroxisome proliferation (5); however, carcinogenicity by this mechanism is unlikely to be relevant to humans (6,7). Several phthalates, DEHP, dibutyl phthalate (DBP), and benzyl butyl phthalate (BzBP), are teratogenic in animals (8-10). DBP is also toxic to the testes, possibly through its metabolite, monobutyl phthalate (MBP) (11,12); other phthalate metabolites, monobenzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), are Sertoli cell toxicants and teratogens in animals (13,14). Furthermore, administration of DBP and DEHP to pregnant rats interferes with normal fetal development in male offspring (15). Regarding reproductive and developmental effects, phthalates vary in potency, with DEHP being the most potent and DBP and BzBP roughly an order of magnitude less potent (8)(9)(10)(11)(12)(13)(14)(15).Based on the varied toxicities of phthalates, internal dose measurements of specific phthalates and their monoester metabolites (16) are important for exposure assessment, and ultimately for accurate human risk assessment. Previous methods for assessing human exposure to phthalates have been subject to laboratory and sample-collection contamination problems from these environmentally ubiquitous compounds (17)(18)(19)(20). For this reason, previous measurements of internal phthalate dose have focused on highly exposed people (21,22). As the primary urinary metabolite, phthalate monoesters are useful biomarkers of specific phthalate exposure.We report the urinary phthalate monoester levels for a human reference population using a new, highly selective technique (23). This analytical approach allows us to directly measure the individual phthalate metabolites responsible for the reproductive and developmental toxicity of phthalates in animals while avoiding contamination from the ubiquitous parent compound. The metabolites measured are monoethyl phthalate (MEP), MBP, MBzP, mono-n-octyl phthalate, MEHP, and mono-3-methyl-5-dimethylhexyl phthalate (monoisononyl, MINP). Commercially used di-isononyl p...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population

Blount¹,

Silva²,

Caudill³

et al. 2000

Environmental Health Perspectives

115

147

View full text Add to dashboard Cite

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“…We are continuously exposed to phthalates and it has been reported that exposure to phthalate esters not only alters the structure of the seminiferous tubules, but can also promote the detachment of germ cells in SC:germ cell coculture systems [96,97]. Besides, they also induce morphologic changes in SCs [98].…”

Section: Relevance Of Metabolic Cooperation In Testis In Pharmacologimentioning

confidence: 99%

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

Alves¹,

Dias²,

Silva³

et al. 2015

CMP

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Abstract:The development of a "male pill" to control fertility is still a major challenge. Although women have several options to play an active role in the couple family planning, men are very limited in terms of contraceptive methods. Several approaches have been proposed to develop a male contraceptive and can be divided in two major groups: hormonal and non-hormonal methods. Within the testis, the somatic Sertoli cell (SC) is known as the "nurse cell" since it provides the physical and nutritional support for the developing germ cells. Moreover, adjacent SCs form the Sertoli/blood testis barrier (BTB), which divides the seminiferous epithelium into the basal and the apical compartments, controlling the passage of substances to the site where germ cells develop. Among the several functions of SC, its metabolism and the production of lactate, acetate and other metabolic factors are essential for the normal occurrence of spermatogenesis. In the last years, several works have highlighted that the metabolic cooperation established between SCs and developing germ cells is compromised in several diseases associated with male subfertility/infertility. Notably, several metabolismassociated proteins are specifically expressed in the testis. Thus, there are several evidences illustrating that the control of male fertility can be achieved by targeting testicular cells metabolism. Herein, we discuss the metabolic cooperation in testis as a potential pharmacological target to counteract subfertility/infertility promoted by several diseases, particularly metabolic diseases. We also discuss how it can contribute to the development of a male contraceptive.

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Assessment of the U.S. Environmental Protection Agency methods for identification of hazards to developing organisms, Part I: The reproduction and fertility testing guidelines

1999

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Background Successful reproduction depends on the coordination of many processes, particularly the normal development and subsequent maturation of the sexual organs. The Food Quality Protection Act of 1996 mandates that the U.S. Environmental Protection Agency must protect infants and children from the effects of toxins, including those that affect the reproductive system. Therefore, the Agency finds itself at a critical juncture to make sure that the methods it requires for toxicity testing, the Health Effects Test Guidelines or Series 870 Guidelines, are adequate to determine possible toxicity to children. Methods and Results We found that two testing protocols included in the core guidelines assess toxicological effects on developing animals. This article aims to provide a detailed analysis of the protocols included in the Reproduction and Fertility Effects Test Guideline. An accompanying article assesses the Developmental Toxicity Testing Guideline. We conducted this analysis on the basis of whether the test would yield the information needed to adequately determine risk to infants and children. Conclusions Our analysis concludes that given the limitations inherent in testing for reproduction and fertility effects during development, it is necessary to include a safety factor during risk assessment of chemicals. This action will fulfill the mandate expressed in the FQPA to protect infants and children from environmental hazards. Am. J. Ind. Med. 35:543–553, 1999. © 1999 Wiley‐Liss, Inc.

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Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells

Cited by 219 publications

References 18 publications

Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population

Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

Assessment of the U.S. Environmental Protection Agency methods for identification of hazards to developing organisms, Part I: The reproduction and fertility testing guidelines

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