Faculty Opinions recommendation of Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals.

2015 ◽  
Author(s):  
Martin van den Berg ◽  
Milou Dingemans
Keyword(s):  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Maternal Exposure ◽  
Behavioral Toxicity ◽  
Endocrine Disrupting

scholarly journals Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals

2014 ◽  
Vol 45 ◽  
pp. 121-130 ◽  
Author(s):  
Marissa Sobolewski ◽  
Katherine Conrad ◽  
Joshua L. Allen ◽  
Hiromi Weston ◽  
Kyle Martin ◽  
...  
Keyword(s):  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Maternal Exposure ◽  
Behavioral Toxicity ◽  
Endocrine Disrupting

Choice of animal feed can alter fetal steroid levels and mask developmental effects of endocrine disrupting chemicals

2011 ◽  
Vol 2 (1) ◽  
pp. 36-48 ◽  
Author(s):  
R. L. Ruhlen ◽  
J. A. Taylor ◽  
J. Mao ◽  
J. Kirkpatrick ◽  
W. V. Welshons ◽  
...  
Keyword(s):  
Low Dose ◽  
Animal Feed ◽  
Endocrine Disrupting Chemicals ◽  
In Utero ◽  
High Dose ◽  
Serum Estradiol ◽  
Toxicological Studies ◽  
Endocrine Disrupting ◽  
Health And Disease ◽  
Daily Sperm Production

Exposure of fetuses to endocrine disrupting chemicals (EDCs), such as the estrogenic drug diethylstilbestrol (DES), disrupts development of the reproductive system and affects other aspects of adult phenotype including diseases, consistent with the developmental origins of health and disease hypothesis. To determine whether diet could influence the effects of DES, we compared mice fed a commonly used combination of soy-based Purina 5008 (breeding and lactation) and 5001 (post-weaning) with mice fed soy-based Purina 5002 throughout life. We exposed fetal CD-1 mice (F1) in utero on different feeds to a 0 (controls), low (0.1 μg/kg/day) or high (50 μg/kg/day) dose of DES via feeding the dam (F0) on gestation days 11–17. Compared to 5008, 5002 feed significantly increased serum estradiol in control fetuses. On 5008 (but not 5002) feed, DES significantly increased fetal serum estradiol at a low dose and reduced it at a high dose. Diet influenced the effects of in utero DES on F1 female onset of puberty and the uterine response to estradiol (an inverted-U dose–response relationship seen for DES on uterine weight with 5008/5001 feed was not observed with 5002). Both low- and high-dose DES reduced daily sperm production (DSP) in adult F1 males on 5008/5001 feed, whereas males fed 5002 showed no DES-induced reduction in DSP. Thus, we observed a number of low-dose effects of in utero DES exposure on Purina 5008/5001 feed that were not observed using Purina 5002, a feed commonly used in industry-funded toxicological studies conducted for regulatory purposes.

scholarly journals Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

2012 ◽  
Vol 33 (3) ◽  
pp. 378-455 ◽  
Author(s):  
Laura N. Vandenberg ◽  
Theo Colborn ◽  
Tyrone B. Hayes ◽  
Jerrold J. Heindel ◽  
David R. Jacobs ◽  
...  
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Low Doses ◽  
Response Curves ◽  
Toxicological Studies ◽  
Endocrine Disrupting ◽  
Dose Effects ◽  
Dose Response Curves ◽  
Low Dose Effects

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.

scholarly journals Low Dose of Genistein Alleviates Mono-(2-Ethylhexyl) Phthalate-Induced Fetal Testis Disorder Based on Organ Culture Model

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Tong-Dian Zhang ◽  
Yu-Bo Ma ◽  
He-Cheng Li ◽  
Tie Chong ◽  
Zi-Ming Wang ◽  
...  
Keyword(s):  
Organ Culture ◽  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Fetal Testis ◽  
Fetal Rat ◽  
Culture Model ◽  
Endocrine Disrupting ◽  
Testicular Histology ◽  
Ethylhexyl Phthalate ◽  
Antioxidative Action

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein have been classified as endocrine-disrupting chemicals (EDCs) which interfere with the differentiation and development of the male reproductive system. However, how these two EDCs would affect fetal rat testis development at a low dose was rarely studied. In this study, we established the organ culture system and applied it to evaluate testicular effects following multiple EDC exposure at a low dose. 15.5 days postcoitum fetal rat testes were dissected, cultured, and exposed to vehicle (control), GEN (1 μmol/L, G), MEHP (1 μmol/L, M), or GEN (1 μmol/L)+MEHP (1 μmol/L, G+M). Testicular cell markers, testosterone concentration, redox state, testicular histology, and testicular ultrastructure were evaluated. Our results showed that a low dose of MEHP suppressed the development of Sertoli cells, Leydig cells, and gonocytes by triggering oxidative injuries, which was consistent with the ultrastructural findings. However, coadministration of genistein at a low dose could partially attenuate MEHP-induced fetal testis damage through antioxidative action. Cotreatment of genistein at a low dose may have a promising future on its protecting role for attenuating other EDC-induced reproductive disorders during early life. Based on the results, it can be speculated that dietary intake of isoflavones may make the fetal testis less susceptible to phthalate-induced injury.

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