* 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.
=>1.〜に慣れて, 2.用いられた, 中古の
Overview of verb use
The verb use has 6 senses (first 3 from tagged texts)
1. (603) use, utilize, utilise, apply, employ -- (put into service; make work or employ for a
particular purpose or for its inherent or natural purpose; "use your head!"; "we only use Spanish at
home"; "I can't use this tool"; "Apply a magnetic field here"; "This thinking was applied to many
projects"; "How do you utilize this tool?"; "I apply this rule to get good results"; "use the
plastic bags to store the food"; "He doesn't know how to use a computer")
2. (12) use, habituate -- (take or consume (regularly or habitually); "She uses drugs rarely")
3. (8) use, expend -- (use up, consume fully; "The legislature expended its time on school
questions")
4. use -- (seek or achieve an end by using to one's advantage; "She uses her influential friends to
get jobs"; "The president's wife used her good connections")
5. practice, apply, use -- (avail oneself to; "apply a principle"; "practice a religion"; "use care
when going down the stairs"; "use your common sense"; "practice non-violent resistance")
6. use -- (habitually do something (use only in the past tense); "She used to call her mother every
week but now she calls only occasionally"; "I used to get sick when I ate in that dining hall";
"They used to vacation in the Bahamas")
Overview of adj used
The adj used has 3 senses (first 3 from tagged texts)
1. (4) used -- (employed in accomplishing something; "the principle of surprise is the most used and
misused of all the principles of war"- H.H.Arnold & I.C.Eaker)
2. (1) exploited, ill-used, put-upon, used, victimized, victimised -- (of persons; taken advantage
of; "after going out of his way to help his friend get the job he felt not appreciated but used")
3. (1) secondhand, used -- (previously used or owned by another; "bought a secondhand (or used)
car")
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