FRAME's historical involvement in the development of the principles of validation, whereby the reliability and relevance of a procedure are established for a specific purpose, and in the practical application of the process, is summarised, and examples of participation in various validation studies on in vitro tests are reviewed. Emphasis is placed on the need for a parallel invalidation process, and on the role of ATLA as a forum for objective reporting and discussion on all aspects of the validation process.
BallsM. & BridgesJ.W. (1984). The FRAME research programme on in vitro cytotoxicology. In Acute Toxicity Testing (ed. GoldbergA.M.), Alternative Methods in Toxicology 2, 61–79. New York, NY, USA: Mary Ann Liebert, Inc.
2.
BallsM. & HornerS.J. (1985). The FRAME interlaboratory programme on in vitro cytotoxicology. Food & Chemical Toxicology23, 209–213.
3.
KnoxP., UphillP.F., FryJ.R., BenfordD.J. & BallsM. (1986). The FRAME multicentre project in in vitro cytotoxicology. Food & Chemical Toxicology24, 457–464.
4.
Anon. (1984). Government grant for FRAME research. ATLA12, 2.
5.
BallsM., RiddellR.J., HornerS.A., & ClothierR.H. (1987). The FRAME approach to the development, validation, and evaluation of in vitro alternative methods. In In Vitro Toxicology: Approaches to Validation (ed. GoldbergA.M.), Alternative Methods in Toxicology 5, 45–58. New York, NY, USA: Mary Ann Liebert, Inc.
6.
PurchaseI.F.H., FarrarD.G. & WhitakerI.A. (1987). Toxicology profiles on substances used in the FRAME cytotoxicology research project. ATLA14, 184–242.
7.
BrantomP.G., AspinP. & ThompsonC. (1995). Supply, coding and distribution of samples for validation studies. ATLA23, 348–351.
8.
BallsM., BlaauboerB., BrusickD., FrazierJ., LambD., PembertonM., ReinhardtC., RoberfroidM., RosenkranzH., SchmidB., SpielmannH., StammatiA-L. & WalumE. (1990). Report and recommendations of the CAAT/ERGATT workshop on the validation of toxicity test procedures. ATLA18, 313–337.
9.
BallsM., BothamP., CordierA., FumeroS., KayserD., KoëterH., KoundakjianP., LindquistN.G., MeyerO., PiodaL., ReinhardtC., RozemondH., SmyrniotisT., SpielmannH., Van LooyH., van der VenneM-T. & WalumE. (1990). Report and recommendations of an international workshop on promotion of the regulatory acceptance of validated non-animal toxicity test procedures. ATLA18, 339–344.
10.
BallsM., BothamP.A., BrunerL.H. & SpielmannS. (1995). The EC/HO international validation study on alternatives to the Draize eye irritation test. Toxicology in Vitro9, 871–929.
11.
BrantomP.G., BrunerL.H., ChamberlainM., de SilvaO., DupuisJ., EarlL.K., LovellD.P., PapeW.J.W., UttleyM., BagleyD.M., BakerF.W., BracherM., CourtellemontP., DeclercqL., FreemanS., SteilingW., WalkerA.P., CarrG.J., DamiN., ThomasG., HarbellJ., JonesP.A., PfannenbeckerU., SoutheeJ.A., TchengM., ArgembeauxH., CastelliD., ClothierR., EsdaileD.J., ItigakiH., JunkK., KasaiY., KojimaH., KristenU., LarnicolM., LewisR.W., MarenusK., MorenoO., PetersonA., RasmussenE.S., RoblesC. & SternM. (1997). A summary report of the COLIPA international validation study on alternatives to the Draize rabbit eye irritation test. Toxicology in Vitro11, 141–179.
12.
BrunerL.H., CarrG.J., ChamberlainM. & CurrenR.D. (1996). Validation of alternative methods for toxicity testing. Toxicology in Vitro10, 479–501.
13.
ArcherG., BallsM., BrunerL.H., CurrenR.D., FentemJ.H., HolzhütterH-G., LiebschM., LovellD.P. & SoutheeJ.A. (1997). The validation of toxicological prediction models. ATLA25, 505–516.
14.
SpielmannH., BallsM., BrandM., DöringB., HolzhütterH.G., KalweitS., KlecakG., L'EpattenierH., LiebschM., LovellW.W., MaurerT., MoldenhauerF., MooreL., PapeW.J.W., PfannenbeckerU., PotthastJ., de SilvaO., SteilingW. & WillshawA. (1994). EC/COLIPA project on in vitro phototoxicity testing: first results obtained with the Balb/c 3T3 cell phototoxicity assay. Toxicology in Vitro8, 793–796.
15.
SpielmannH., BallsM., DupuisJ., PapeW.J., PechovitchG., de SilvaO., HolzhütterH.G., ClothierR., DesolleP., GerberickF., LiebschM., LovellW.W., MaurerT., PfannenbeckerU., PotthastJ.M., CsatoM., SladowskiD., SteilingW. & BrantomP. (1998). The international EU/COLIPA in vitro phototoxicity validation study: Results of phase II (blind trial). Part 1: The 3T3 NRU phototoxicity test. Toxicology in Vitro12, 305–327.
16.
SpielmannH., BallsM., DupuisJ., PapeW.J.W., de SilvaO., HolzhütterH.G., GerberickF., LiebschM., LovellW.W. & PfannenbeckerU. (1998). A study on UV filter chemicals from Annex VII of European Union Directive 76/768/EEC, in the in vitro 3T3 NRU phototoxicity test. ATLA26, 679–708.
17.
ClothierR., WillshawA., CoxH., GarleM., BowlerH. & CombesR. (1999). The use of human keratinocytes in the EU/COLIPA international in vitro phototoxicity test validation study and the ECVAM/COLIPA study on UV filter chemicals. ATLA27, 247–259.
18.
HolzhütterH.G. (1997). A general measure of in vitro phototoxicity derived from pairs of dose–response curves and its use for predicting phototoxicity of chemicals. ATLA25, 445–462.
19.
BallsM., BlaauboerB.J., FentemJ.H., BrunerL., CombesR.D., EkwallB., FielderR.J., GuillouzoA., LewisR.W., LovellD.P., ReinhardtC.A., RepettoG., SladowskiD., SpielmannH. & ZuccoF. (1995). Practical aspects of the validation of toxicity test procedures. The report and recommendations of ECVAM workshop 5. ATLA23, 129–147.
20.
BarrattM.D., BrantomP.G., FentemJ.H., GernerI., WalkerA.P. & WorthA.P. (1998). The ECVAM international validation study on in vitro tests for skin corrosivity. 1. Selection and distribution of the test chemicals. Toxicology in Vitro12, 471–482.
21.
FentemJ.H., ArcherG.E.B., BallsM., BothamP.A., CurrenR.D., EarlL.K., EsdaileD.J., HolzhütterH.G. & LiebschM. (1998). The ECVAM international validation study on in vitro tests for skin corrosivity. 2. Results and evaluation by the Management Team. Toxicology in Vitro12, 483–524.
22.
CurrenR.D., SoutheeJ.A., SpielmannH., LiebschM., FentemJ.H. & BallsM. (1995). The role of prevalidation in the development, validation and acceptance of alternative methods. ATLA23, 211–217.
23.
BallsM. & KarcherW. (1995). The validation of alternative test methods. ATLA23, 884–886.
24.
SpielmannH., LiebschM. & ReinhardtC. (1998). ERGATT/ECVAM Workshop zur Akzeptierung validierter Alternativmethoden: Amden III. ALTEX15, 18–22.
25.
Cooper-HannanR., HarbellJ.W., CoeckeS., BallsM., BoweG., CervinkaM., ClothierR., HermannF., KlahmL.K., de LangeJ., LiebschM. & VanparysP. (1999). The principles of good laboratory practice: application to in vitro toxicological studies. The report and recommendations of ECVAM workshop 37. ATLA27, 539–577.
26.
BallsM., AmcoffP., BremerS., CasatiS., CoeckeS., ClothierR., CombesR., CorviR., CurrenR., EskesC., FentemJ., GribaldoL., HalderM., HartungT., HoffmannS., SchechtmanL., ScottL., SpielmannH., StokesW., TiceR., WagnerD. & ZuangV. (2006). The principles of weight-of-evidence validation of test methods and testing strategies. The report and recommendations of ECVAM Workshop 58. ATLA34, 603–620.
27.
BallsM. (1997). Defined structural and performance criteria would facilitate the validation and acceptance of alternative test procedures. ATLA25, 483–484.
28.
LiebschM., TraueD., BarrabasC., SpielmannH., UphillP., WilkinsS., McPhersonJ.P., WiemannC., KaufmannT., RemmeleM. & HolzhütterH.G. (2000). The ECVAM prevalidation study on the use of EpiDerm for skin corrosivity testing. ATLA28, 371–401.
29.
Anon. (2000). ESAC (ECVAM Scientific Advisory Committee) Statement on the application of the EpiDerm™ human skin model for skin corrosivity testing. ATLA28, 365–367.
30.
KandárováH., HaydenP., KlausnerM., KubilusJ., KearneyP. & SheasgreenJ. (2009). In vitro skin irritation testing: Improving the sensitivity of the EpiDerm Skin Irritation Test protocol. ATLA37, 671–689.
31.
CombesR.D., GauntI. & BallsM. (2004). A scientific and animal welfare assessment of the OECD Health Effects Test Guidelines for the safety testing of chemicals under the European Union REACH system. ATLA32, 163–208.
32.
BallsM. & CombesR. (2005). The need for a formal invalidation process for animal and non-animal tests. ATLA33, 299–308.
33.
ClothierR.H., HulmeL., AhmedA.B., ReevesH.L., SmithM. & BallsM. (1988). In vitro cytotoxicity of 150 chemicals to 3T3-L1 cells, assessed by the FRAME kenacid blue method. ATLA16, 84–95.
34.
HulmeL.M., ReevesH.L, ClothierR.H., SmithM. & BallsM. (1987). An assessment of two alternative methods for predicting the in vivo toxicities of metallic compounds. Molecular Toxicology1, 589–596.
35.
BorenfreundE. & PuernerJ.A. (1985). Toxicity determined in vitro by morphological alteration and neutral red absorption. Toxicology Letters24, 119–124.
36.
ClemedsonC., McFarlane-AbdullaE., AnderssonM., BarileF.A., CallejaM.C., ChesnéC., ClothierR., CottinM., CurrenR., Daniel-SzolgayE., DierickxP., FerroM., Fiskesjö, G., Garza-Ocañas, L., Gómez-LechónM.J., GüldenM., IsomaaB., JanusJ., JudgeP., KahruA., KempR.B., KerszmanG., KristenU., KunimotoM., KärenlampiS., LavrijsenK., LewanL., LiliusH., OhnoT., PersooneG., RoguetR., RomertL., SawyerT.W., SeibertH., ShrivastavaR., StammatiA., TanakaN., Torres-AlanisO., VossJ-U., WakuriS., WalumE., WangX., ZuccoF. & EkwallB. (1996). MEIC evaluation of systemic toxicity. Part 1. Methodology of 68 in vitro toxicity assays used to test the first 30 reference chemicals. ATLA24, 251–272.
37.
ClemedsonC., McFarlane-AbdullaE., AnderssonM., BarileF.A., CallejaM.C., ChesnéC., ClothierR., CottinM., CurrenR., DierickxP., FerroM., FiskesjöG., Garza-OcañasL., Gómez-LechónM.J., GüldenM., IsomaaB., JanusJ., JudgeP., KahruA., KempR.B., KerszmanG., KristenU., KunimotoM., KärenlampiS., LavrijsenK., LewanL., LiliusH., MalmstenA., OhnoT., PersooneG., PetterssonR., RoguetR., RomertL., SandbergM., SawyerT.W., SeibertH., ShrivastavaR., SjöströmM., StammatiA., TanakaN., Torres-AlanisO., VossJ-U., WakuriS., WalumE., WangX., ZuccoF. & EkwallB. (1996). MEIC evaluation of systemic toxicity. Part 2. In vitro results from 68 toxicity assays used to test the first 30 reference chemicals and a comparative analysis. ATLA24, 273–311.
38.
ClothierR., GottschalgE., CasatiS. & BallsM. (2006). The FRAME Alternatives Laboratory Data-base. 1. In vitro basal cytotoxicity determined by the kenacid blue total protein assay. ATLA34, 151–175.
39.
SmithL.M., ClothierR.H., HillidgeS. & BallsM. (1992). Modification of the FRAME kenacid blue method for cytotoxicity tests on volatile materials. ATLA20, 230–234.
40.
HulmeL.M., AtkinsonK.A., ClothierR.H. & BallsM. (1990). The potential usefulness of a differentiating teratocarcinoma cell line in in vitro toxicity testing. Toxicology in Vitro4, 589–592.
41.
StricklandJ., StokesW.S., CasatiS., ParisM., WorthM., RaabeH., CaoC., ClothierR., HarbellJ., CurrenR., HasemanJ. & TiceR. (2003). Design of a validation study to evaluate in vitro cytotoxicity for predicting rodent and human acute systemic toxicity. Toxicologist72, 157 (Abstract 761).
42.
ParisM., StricklandJ., StokesW., CasatiS., TiceR., RaabeH., CaoC., ClothierR., HarbellJ., MunG., SizemoreA., MoyerG., Madren-WhalleyJ., KrishnaC., OwenM., BourneN., HasemanJ., CrockettP., WenkM. & VallantM. (2005). Protocol optimization during a validation study to evaluate in vitro cytotoxicity assays for estimating rodent acute systemic toxicity. ALTEX22, Special Issue, 193 (poster abstract).
43.
StricklandJ., ParisM., RaabeH., HasemanJ., CasatiS., ClothierR., CaoC., CrockettP., TiceR. & StokesW. (2005). Data collection and analysis for an in vitro cytotoxicity validation study. ALTEX22, Special Issue, 197 (poster abstract).
44.
WattsS., BudworthR., BourneN., OwenM. & ClothierR. (2005). Comparison of two cytotoxicity assays with the ICCVAM/ECVAM validation study chemicals. ALTEX22, Special Issue, 198 (poster abstract).
45.
StokesW., ParisM., StricklandJ., CasatiS., TiceR., RaabeH., CaoC., ClothierR., HarbellJ., MunG., SizemoreA., MoyerG., Madren-WhalleyJ., KrishnaC., OwenM., BourneN., HasemanJ., CrockettP., HarveyE., LeeR., WentM. & VallantM. (2005). Results of the final phase of a validation study to evaluate in vitro cytotoxicity assays for estimating rodent acute systemic toxicity. ALTEX22, Special Issue, 196 (poster abstract).
ClemedsonC., KolmanA. & ForsbyA. (2007). The integrated Acute Systemic Toxicity Project (ACuteTox) for the optimisation and validation of alternative in vitro tests. ATLA35, 33–38.
48.
ClothierR., DierickxP., LakhaniskyT., FabreM., BetanzosM., CurrenR., SjöströmM., RabbeH., BourneN., HernandezV., MainezJ., OwenM., WattsS. & AnthonissenR. (2008). A database of IC50 values and principal component analysis of six basal cytotoxicity assays, for use in the modelling of the in vivo and in vitro data of the EU ACuteTox project. ATLA36, 1–17.
49.
SjöströmM., KolmanA., ClemedsonC. & ClothierR. (2008). Estimation of human blood LC50 values for use in modeling of in vitro–in vivo data of the ACuteTox project. Toxicology in Vitro22, 1405–1411.
50.
CombesR. (2007). The FRAME Research Programme under the direction of Dr Richard Clothier. ATLA35, 525–530.
51.
HartungT., BremerS., CasatiS., CoeckeS., CorviR., FortanerS., GribaldoL., HalderM., HoffmannS., Janusch RoiA., PrietoP., SabbioniE., ScottL., WorthA. & ZuangV. (2004). A modular approach to the ECVAM principles on test validity. ATLA32, 467–472.
ScottL., EskesC., HoffmannS., AdriaensE., AlepéeN., BufoM., ClothierR., FacchiniD., FallerC., GuestR., HarbellJ., HartungT., KampH., Le VarletB., MeloniM., McNameeP., OsborneR., PapeW., PfannenbeckerU., PrinsenM., SeamanC., SpielmannH., StokesW., TroubaK., Van den BergheC., Van GoethemF., VassalloM., VinardellP. & ZuangV. (2010). A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-up and Top-down approaches. Toxicology in Vitro24, 1–9.
54.
FlintO.P. (1992). In vitro test validation: A house built on sand. ATLA20, 196–198.
55.
BallsM. (1992). In vitro test validation: High hurdling, but not pole vaulting. ATLA20, 355–357.
56.
WalumE. (1992). In vitro test validation: Should it obey laws, recognise uncertainty principles or follow scientific practices?ATLA20, 502–503.
57.
DickensM., KruszewskiF. & GordonV.G. (1992). In vitro test validation: The winds of change. ATLA20, 563–564.
58.
ZuccoF. (1992). In vitro test validation: No room for conflict with “mechanistic” studies. ATLA20, 565–566.
59.
GreenS. (1992). In vitro test validation and regulatory animal testing: A house built on sand versus a house of cards. ATLA20, 567–570.
60.
BallsM. (2009). Animal experimentation and the Three Rs: Time for honest answers to some leading questions. ATLA37, 229–232.
