کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6313260 | 1619045 | 2015 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Towards a non-animal risk assessment for anti-androgenic effects in humans
ترجمه فارسی عنوان
به سوی یک ارزیابی خطر غیر حیوانی برای اثرات ضد آندروژنیک در انسان
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کلمات کلیدی
DHTToxicology testingEDSPQIVIVEMIEIGDOCT1MMTVLOECIHD5α-RBPADPBPKOECDCHHIL-6hptADMEPhysiologically-based pharmacokinetic modellingAOPNRCEndocrine disrupter - اختلال غدد درون ریزAndrographolide - اندوگرافولیدHCG - اچ سی جیinterleukin-6 - اینترلوکین ۶testosterone - تستوسترونabsorption, distribution, metabolism and excretion - جذب، توزیع، متابولیسم و دفعDihydrotestosterone - دی هیدروتستوسترونmolecular initiating event - رویداد آغازین مولکولیOrganization for Economic Cooperation and Development - سازمان همکاری های اقتصادی و توسعهNational Research Council - شورای تحقیقات ملیyeast androgen screen - صفحه نمایش آندروژن مخمرAnogenital distance - فاصله آنومالیadverse outcome pathway - مسیر ناخوشایندAdverse outcome - نتیجه منفیHCG, Human chorionic gonadotropin - هورمون اچسیجی، گنادوتروپین جفتی انسانmouse mammary tumour virus - ویروس تومور پستان موشAGD - کالاهای خانگیlowest observed effect concentration - کمترین اثر غلظت مشاهده شدهAndrogen Receptor - گیرنده آندروژنیoestrogen receptor - گیرنده استروژنYAS - یاس
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
شیمی زیست محیطی
چکیده انگلیسی
Toxicology testing is undergoing a transformation from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. We review the tools and approaches that could be used to develop a non-animal safety assessment for anti-androgenic effects in humans, with a focus on the molecular initiating events (MIEs) that human disorders indicate critical for normal functioning of the hypothalamus-pituitary-testicular (HPT) axis. In vitro test systems exist which can be used to characterize the effects of test chemicals on some MIEs such as androgen receptor antagonism, inhibition of steroidogenic enzymes or 5α-reductase inhibition. When used alongside information describing the pharmacokinetics of a specific chemical exposure, these could be used to inform a pathways-based safety assessment. However, some parts of the HPT axis such as events occurring in the hypothalamus or pituitary are not well represented by accepted in vitro methods. In vitro tools to characterize perturbations in these events need to be developed before a fully integrated model of the HPT axis can be described. Knowledge gaps also exist which prevent us from using in vitro data to predict the type and severity of in vivo effect(s) that could arise from a given level of in vitro anti-androgenic activity. This means that more work is needed to reliably link an MIE with an adverse outcome. However, especially for chemicals with low anti-androgenic activity, human exposure data can be used to put in vitro mode of action data into context for risk-based safety decision-making.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Environment International - Volume 83, October 2015, Pages 94-106
Journal: Environment International - Volume 83, October 2015, Pages 94-106
نویسندگان
Matthew P. Dent, Paul L. Carmichael, Kevin C. Jones, Francis L. Martin,