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421954 occurrences (No.40 in the rank) during 5 years in the PubMed. [no cache] 500 found

321) Challenges to improve toxicological risk assessment to meet the demands of the EU chemical's legislation, REACH, and the EU 7th Amendment of the Cosmetics Directive have accelerated the development of non-animal based methods.

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PMID:23978460 DOI:10.1016/j.tox.2013.08.012

2015 Toxicology

* Dose metric considerations in in vitro assays to improve quantitative in vitro-in vivo dose extrapolations.

- Challenges to improve toxicological risk assessment to meet the demands of the EU chemical's legislation, REACH, and the EU 7th Amendment of the Cosmetics Directive have accelerated the development of non-animal based methods. Unfortunately, uncertainties remain surrounding the power of alternative methods such as in vitro assays to predict in vivo dose-response relationships, which impedes their use in regulatory toxicology. One issue reviewed here, is the lack of a well-defined dose metric for use in concentration-effect relationships obtained from in vitro cell assays. Traditionally, the nominal concentration has been used to define in vitro concentration-effect relationships. However, chemicals may differentially and non-specifically bind to medium constituents, well plate plastic and cells. They may also evaporate, degrade or be metabolized over the exposure period at different rates. Studies have shown that these processes may reduce the bioavailable and biologically effective dose of test chemicals in in vitro assays to levels far below their nominal concentration. This subsequently hampers the interpretation of in vitro data to predict and compare the true toxic potency of test chemicals. Therefore, this review discusses a number of dose metrics and their dependency on in vitro assay setup. Recommendations are given on when to consider alternative dose metrics instead of nominal concentrations, in order to reduce effect concentration variability between in vitro assays and between in vitro and in vivo assays in toxicology.

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(1)138 of	(9)9 in	(17)4 factors,	(25)2 managers
(2)72 factors	(10)7 group	(18)4 stratification	(26)2 mortality
(3)40 for	(11)6 ratio	(19)4 was	(27)2 perception
(4)24 factor	(12)5 behavior	(20)3 groups	(28)2 rates
(5)23 and	(13)5 is	(21)3 infants	(29)2 the
(6)16 null	(14)5 patients	(22)2 among
(7)13 assessment	(15)5 to	(23)2 during
(8)10 score	(16)4 areas	(24)2 estimators

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--- WordNet output for risk --- =>1.損害の恐れ, 危険, 冒険, リスク, 2.危険にさらす, 3.敢えてする, 被保険者, 被保険物, 危険にさらす, 賭けてみる Overview of noun risk The noun risk has 4 senses (first 2 from tagged texts) 1. (4) hazard, jeopardy, peril, risk, endangerment -- (a source of danger; a possibility of incurring loss or misfortune; "drinking alcohol is a health hazard") 2. (2) risk, peril, danger -- (a venture undertaken without regard to possible loss or injury; "he saw the rewards but not the risks of crime"; "there was a danger he would do the wrong thing") 3. risk, risk of infection -- (the probability of becoming infected given that exposure to an infectious agent has occurred) 4. risk, risk of exposure -- (the probability of being exposed to an infectious agent) Overview of verb risk The verb risk has 2 senses (first 2 from tagged texts) 1. (8) risk, put on the line, lay on the line -- (expose to a chance of loss or damage; "We risked losing a lot of money in this venture"; "Why risk your life?"; "She laid her job on the line when she told the boss that he was wrong") 2. (2) gamble, chance, risk, hazard, take chances, adventure, run a risk, take a chance -- (take a risk in the hope of a favorable outcome; "When you buy these stocks you are gambling") --- WordNet end ---