کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5561156 1562115 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lessons learned from read-across case studies for repeated-dose toxicity
ترجمه فارسی عنوان
درسهایی که از مطالعات موردی برای مقادیر مکرر دوز استفاده شده است
کلمات کلیدی
خواندن در سراسر، شباهت، عدم قطعیت، مطالعات موردی، سمیت دوزهای مجاز، پذیرش مقرراتی،
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


- Read-across case studies for repeated-dose toxicity were evaluated.
- Identification and definition of uncertainties in read-across is crucial.
- The logic and data leading to a read-across prediction must be documented.
- The similarity rationale of a read-across should be described transparently.
- The roles of any endpoint specific and/or non-specific factors should be clarified.

A series of case studies designed to further acceptance of read-across predictions, especially for chronic health-related endpoints, have been evaluated with regard to the knowledge and insight they provide. A common aim of these case studies was to examine sources of uncertainty associated with read-across. While uncertainty is related to the quality and quantity of the read across endpoint data, uncertainty also includes a variety of other factors, the foremost of which is uncertainty associated with the justification of similarity and quantity and quality of data for the source chemical(s). This investigation has demonstrated that the assessment of uncertainty associated with a similarity justification includes consideration of the information supporting the scientific arguments and the data associated with the chemical, toxicokinetic and toxicodynamic similarity. Similarity in chemistry is often not enough to justify fully a read-across prediction, thus, for chronic health endpoints, toxicokinetic and/or toxicodynamic similarity is essential. Data from New Approach Methodology(ies) including high throughput screening, in vitro and in chemico assay and in silico tools, may provide critical information needed to strengthen the toxicodynamic similarity rationale. In addition, it was shown that toxicokinetic (i.e., ADME) similarity, especially metabolism, is often the driver of the overall uncertainty.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 88, August 2017, Pages 185-191
نویسندگان
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