A State-of-the-Art Review on the Alternatives to Animal Testing for the Safety Assessment of Cosmetics
Abstract
:1. Introduction
2. Methodology
3. Drivers for the Phasing-Out of Animal Testing in Cosmetics
3.1. Ethical Considerations
3.2. The Lack of Effective Extrapolation
3.3. Economic Efficiency
4. Global Regulatory Responses
4.1. European Union
REACH vs. Regulation EC 1223/2009
4.2. United States
4.3. China
4.4. Rest of the World
5. New Approach Methodologies (NAMs)
Toxicological Endpoint | Name | Testing Method Title | Year Received | Responsible Organisation | Type | OECD Guideline |
---|---|---|---|---|---|---|
Acute toxicity, Basal Cytotoxicity | NRU cytotoxicity | Neutral red uptake for starting doses for acute oral toxicity | 2003 | ICCVAM/NICEATM | in vitro | OECD GD 129 [58] |
3T3 NRU | 3T3 Neutral Red Uptake cytotoxicity assay | 2007 | EURL ECVAM | in vitro | N/A | |
Carcinogenicity | SHE 6.7 CTA | Syrian hamster embryo cell transformation assay at pH 6.7 | 2005 | EURL ECVAM | in vitro | OECD GD 214 [59] |
Carcinogenicity | SHE 7.0 CTA | Syrian hamster embryo cell transformation assay at pH 7.0 | 2005 | EURL ECVAM | in vitro | |
Bhas 42 CTA | Cell Transformation Assay Based on the Bhas 42 Cell Line | 2012 | EURL ECVAM | in vitro | OECD GD 231 [60] | |
Skin Corrosion | TER | Rat skin transcutaneous electrical resistance test 1 | 1995 | EURL ECVAM | ex vivo | OECD TG 430 [61] |
EpiDerm™ | EpiDerm™ skin corrosivity test | 1998 | EURL ECVAM | in vitro | OECD TG 431 [62] | |
Epics SCT | Epidermal Skin Corrosion Test 1000 | 2007 | EURL ECVAM | in vitro | ||
LabCyte EPI-MODEL24 SCT | LabCyte EPI-MODEL24 skin corrosion test | 2017 | JaCVAM | in vitro | ||
EpiSkin™ | EpiSkin™ skin corrosivity test | 1998 | EURL ECVAM | in vitro | ||
Corrositex® | In Vitro Membrane Barrier Test Method for Skin Corrosion | 1998 | EURL ECVAM | in vitro | OECD TG 435 [63] | |
Skin Irritation | LabCyte EPI-MODEL24 SIT | LabCyte EPI-MODEL24 skin irritation test | 2008 | JaCVAM | in vitro | OECD TG 439 [64] |
SkinEthic RHE | Skinethic Skin Irritation Test-42bis | 2008 | EURL ECVAM | in vitro | ||
Modified EpiDerm SIT | Modified EpiDerm Skin Irritation Test for Hazard Identification and Labelling of Chemicals According to EU Classification System | 2008 | EURL ECVAM | in vitro | ||
epiCS SIT | epiCS Skin Irritation Test | 2009 | EURL ECVAM | in vitro | ||
Skin Sensitisation | Murine Local Lymph Node Assay | Murine Local Lymph Node Assay 2 | 1998 | ICCVAM/NICEATM | in vivo | OECD TG 442B [65] |
DPRA | Direct Peptide Reactivity Assay | 2009 | EURL ECVAM | in chemico | OECD TG 442C [66] | |
ADRA for skin sensitization | In Chemico Skin Sensitisation: Amino acid Derivative Reactivity Assay | 2016 | JaCVAM | in chemico | ||
KeratinoSens | KeratinoSens assay for the testing of skin sensitizers | 2010 | EURL ECVAM | in vitro | OECD TG 442D [67] | |
LuSens | LuSens Assay | 2011 | EURL ECVAM | in vitro | ||
U-SENS™ | U-SENS™—Myeloid U937 Skin Sensitisation Test | 2013 | EURL ECVAM | in vitro | OECD TG 442E [68] | |
hCLAT | Human Cell Line Activation Test | 2008 | EURL ECVAM | in vitro | ||
IL-8 Luciferase assay for skin sensitization | IL-8 Luciferase assay for skin sensitization | 2016 | JaCVAM | in vitro | ||
Phototoxicity | EpiDerm-PT | Human 3-D Epidermis Model in Vitro Phototoxicity Test | 1997 | EURL ECVAM | in vitro | OECD TG 498 [69] |
Ros Assay | Ros (Reactive Oxygen Species) Assay for Photoreactivity | 2013 | JaCVAM | in chemico | OECD TG 495 [70] | |
Genotoxicity/ Mutagenicity | MNvit | In vitro mammalian cell micronucleus test | 2005 | EURL ECVAM | in vitro | OECD TG 487 [71] |
Reproductive toxicity, Endocrine disruption | ER-STTA assay | Stably Transfected Human Estrogen Receptor-α Transactivation Assay using the (h) ERα-HeLa-9903 cell line | 2008 | JaCVAM | in vitro | OECD TG 455 [72] |
ERalpha-CALUX | Prediction of the in vivo estrogenic activity of chemicals ERalpha-CALUX | 2009 | EURL ECVAM | in vitro | ||
AR-CALUX | Transactivation assay for detection of androgenic activity of chemicals | 2010 | EURL ECVAM | in vitro | OECD TG 458 [73] | |
AR-Ecoscreen test | Androgen Receptor TransActivation Assay using the stably transfected human AR-EcoScreen™ cell line | 2012 | JaCVAM | in vitro | ||
VM7Luc ER TA | The VM7Luc ER TA test method: An In Vitro Assay for Identifying Human Estrogen Receptor Agonist and Antagonist Activity of Chemicals | 2016 | ICCVAM/NICEATM | in vitro | OECD TG 457 [74] | |
ToxCast ER Pathway Model | The ToxCast Estrogen Receptor Agonist Pathway Model | 2016 | ICCVAM/NICEATM | in silico | N/A | |
Serious eye damage/ Eye irritation | BCOP | Bovine corneal opacity and permeability test method | 2003 | ICCVAM/NICEATM | ex vivo | OECD TG 437 [75] |
ICE | Isolated Chicken Eye | 2003 | ICCVAM/NICEATM | ex vivo | OECD TG 438 [76] | |
FL | The fluorescein leakage test method | 2004 | EURL ECVAM | in vitro | OECD TG 460 [77] | |
Ocular Irritection | Ocular Irritection | 2006 | EURL ECVAM | in vitro | OECD TG 496 [78] | |
STE | Short Time Exposure Test | 2008 | ICCVAM/NICEATM | in vitro | OECD TG 491 [79] | |
EpiOcular EIT | EpiOcular™ Human Cell Construct EIT | 2008 | EURL ECVAM | in vitro | OECD TG 492 [80] | |
LabCyteCORNEAMODEL24 EIT | LabCyteCORNEAMODEL24 eye irritation test | 2015 | JaCVAM | in vitro | ||
SkinEthic HCE EIT | SkinEthic™ HCE Eye Irritation Test | 2015 | EURL ECVAM | in vitro | ||
Vitrigel-Eye Irritancy Test | Vitrigel-Eye Irritancy Test | 2011 | JaCVAM | in vitro | OECD TG 494 [81] |
5.1. Non-Testing Methods: In Silico Toxicology
5.2. Endpoint Specific NAMs
5.2.1. Acute Toxicity
5.2.2. Skin Corrosion/Irritation
5.2.3. Serious Eye Damage/Irritation
5.2.4. Skin Sensitisation
5.2.5. Repeated Dose Toxicity
5.2.6. Reproductive Toxicity/Endocrine Disruption
5.2.7. Mutagenicity/Genotoxicity
5.2.8. Carcinogenicity
5.2.9. Photo-Induced Toxicity
5.2.10. Toxicokinetics
6. Public Perception of Animal Testing in Cosmetics
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Format | Source |
---|---|
Tier 1: Academic Papers |
|
Tier 2: Articles |
|
Tier 3: Reports |
|
Country | Product Testing Ban a | Ingredient Testing Ban b | Marketing Ban c |
---|---|---|---|
United Kingdom | 1998 | 1998 | 2009/13 (as part of EU Regulation EC 1223/2009) |
EU/EFTA | 2004 | 2009 | 2009/13 (depending on the toxicological endpoint) |
Brazil (São Paulo) | 2014 | ||
India | 2014 | ||
New Zealand | 2015 | 2015 | |
Turkey | 2015 (where a validated alternative exists) | 2015 (where a validated alternative exists) | 2015 (where a validated alternative exists) |
South Korea | 2015 (where a validated alternative exists) | 2015 (where a validated alternative exists) | 2015 (where a validated alternative exists) |
Guatemala | 2017 | ||
Brazil (Paraná) | 2015 | ||
Brazil (Pará) | 2016 | ||
Brazil (Rio de Janeiro) | 2017 | 2017 | |
Brazil (Minas Gerais) | 2018 | ||
Brazil (Pernambuco) | 2018 | ||
USA (California) | 2018 | ||
Australia | 2019 | 2019 | |
USA (Illinois, and Nevada) | 2019 | ||
Taiwan | 2019 | 2019 | |
Mexico | 2021 | 2021 | |
Colombia | 2020 | 2020 | |
Brazil (Santa Catarina) | 2020 | ||
Brazil (Federal District) | 2020 | ||
USA (Virginia, Maryland, Maine, Hawaii, and New Jersey) | 2021 | ||
Brazil (Paraíba) | 2022 |
Toxicological Endpoint | Test Methods |
---|---|
Skin Corrosion (OECD TG 431) |
|
Skin Irritation (OECD TG 439) |
|
Group | Test Methods |
---|---|
Organotypic tests Able to identify chemicals that induce serious eye damage (GHS Ca-tegory 1), and chemicals that do not require classification | Bovine Cornea Opacity Permeability (BCOP, OECD TG 437) [75] Determines a test chemical’s ability to cause opacity and permeability in an isolated bovine cornea. Isolated Chicken Eye (ICE, OECD TG 438) [76] Determines a test chemical’s ability to induce toxicity in an enucleated chicken eye. |
Cytotoxicity and cell function-based in vitrotests Able to identify chemicals that induce serious eye damage (GHS Ca-tegory 1), and chemicals that do not require classification | Short Time Exposure (STE, OECD 491) [79] Evaluates eye irritation potential of a test chemical by measuring its cytotoxic effect on a rabbit corneal cell line Fluorescein Leakage (FL, OECD TG 460) [77] Evaluates the toxic effects of a short exposure to a substance by measuring sodium fluorescein permeability through an epithelial monolayer of MDCK kidney cells. |
Reconstructed human tissue (RhT)-based tests Able to identify chemicals that do not require classification | Reconstructed Human Cornea-like Epithelium (RhCE, OECD TG 492) [80] Determines a test chemical’s ability to induce cytotoxicity. Currently four commercially available RhCE models have been adopted: EpiOcular™ EIT, SkinEthicTM Human Corneal Epithelium (HCE) EIT, LabCyte CORNEA-MODEL 24 EIT, and MCTT HCETM EIT. Vitrigel-EIT (OECD TG 494) [81] Determines eye irritation potential of a test chemical by evaluating its ability to induce damage to the barrier function of a hCE model fabricated in a Collagen Vitrigel Membrane (CVM) chamber, by measuring relative changes in transepithelial electrical resistance (TEER) over time. |
In vitro macromolecular test Recommended only as part of a tiered testing strategy, with specific limitations | Ocular Irritection® (OI) assay (OECD TG 496) [78] A biochemical assay that determines ocular toxicity through the premise that eye irritation and corneal opacity result from the denaturation or perturbation of corneal proteins. |
Defined Approach (DA) | Information Sources | Capability (Hazard and/or Potency) |
---|---|---|
‘2 out of 3’ (2o3) DA Able to distinguish chemicals that induce skin sensitisation (GHS Category 1) from chemicals that do not require classification. | KE1 (protein binding): Direct peptide Reactivity assay (DPRA; OECD TG 442C) [66] KE2 (keratinocyte activation): KeratinoSens™ (OECD TG 442D) [67] K3 (dendritic cell activation): Human Cell Line Activation Test (h-CLAT; OECD TG 442E) [68] | Hazard |
Integrated Testing Strategy (ITS) DA Able to distinguish chemicals that induce skin sensitisation (GHS Category 1) from chemicals that do not require classification and allocate skin sensitizers into GHS sub-categories (1A or 1B). | KE1 (protein binding): Direct Peptide Reactivity assay (DPRA; OECD TG 442C) [66] K3 (dendritic cell activation): Human Cell Line Activation Test (h-CLAT; OECD TG 442E) [68] in silico prediction: Derek Nexus v6.1.0 (ITSv1) or OECD QSAR Toolbox v4.5 (ITSv2) | Hazard, Potency |
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Silva, R.J.; Tamburic, S. A State-of-the-Art Review on the Alternatives to Animal Testing for the Safety Assessment of Cosmetics. Cosmetics 2022, 9, 90. https://doi.org/10.3390/cosmetics9050090
Silva RJ, Tamburic S. A State-of-the-Art Review on the Alternatives to Animal Testing for the Safety Assessment of Cosmetics. Cosmetics. 2022; 9(5):90. https://doi.org/10.3390/cosmetics9050090
Chicago/Turabian StyleSilva, Rita José, and Slobodanka Tamburic. 2022. "A State-of-the-Art Review on the Alternatives to Animal Testing for the Safety Assessment of Cosmetics" Cosmetics 9, no. 5: 90. https://doi.org/10.3390/cosmetics9050090