Validation and Regulatory Acceptance of Alternatives

1999 ◽  
Vol 8 (1) ◽  
pp. 73-79 ◽  
Author(s):  
RICHARD N. HILL ◽  
WILLIAM S. STOKES
Keyword(s):  
Ad Hoc ◽  
Toxicity Testing ◽  
Test Method ◽  
Regulatory Agencies ◽  
Eye Irritation ◽  
Current Test ◽  
Irritation Test ◽  
Test Guideline

For years there was no focus within the U.S. federal government for alternatives to animal toxicity testing. Questions coming to regulatory agencies fell upon individuals to address in the best way they could. Given this void, the ad hoc Interagency Regulatory Alternatives Group was founded by staff in a number of federal agencies in the late 1980s to coalesce efforts in the field. The group sponsored two international workshops on eye irritation, the first making proposals for change in the current test method in rabbits, the second reviewing available data on in vitro alternatives. The result has been that the Organization for Economic Cooperation and Development (OECD) is considering revision of the in vivo eye irritation test guideline to incorporate a number of the workshop deliberations. However, movement of the in vitro eye irritation alternatives has been disappointing; attempts to determine their practical testing significance have thus far been unrewarding.

scholarly journals ChemSkin Reference Chemical Database for the Development of an In Vitro Skin Irritation Test

Toxics ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 314
Author(s):  
Juhee Han ◽  
Ga-Young Lee ◽  
Green Bae ◽  
Mi-Jeong Kang ◽  
Kyung-Min Lim
Keyword(s):  
Pearson Correlation ◽  
Skin Irritation ◽  
Test Method ◽  
Predictive Capacity ◽  
Chemical Database ◽  
Irritation Test ◽  
Commercial Sources ◽  
Skin Irritation Test

Since the animal test ban on cosmetics in the EU in 2013, alternative in vitro safety tests have been actively researched to replace in vivo animal tests. For the development and evaluation of a new test method, reference chemicals with quality in vivo data are essential to assess the predictive capacity and applicability domain. Here, we compiled a reference chemical database (ChemSkin DB) for the development and evaluation of new in vitro skin irritation tests. The first candidates were selected from 317 chemicals (source data n = 1567) searched from the literature from the last 20 years, including previous validation study reports, ECETOC, and published papers. Chemicals showing inconsistent classification or those that were commercially unavailable, difficult or dangerous to handle, prohibitively expensive, or without quality in vivo or in vitro data were removed, leaving a total of 100 chemicals. Supporting references, in vivo Draize scores, UN GHS/EU CLP classifications and commercial sources were compiled. Test results produced by the approved methods of OECD Test No. 439 were included and compared using the classification table, scatter plot, and Pearson correlation analysis to identify the false predictions and differences between in vitro skin irritation tests. These results may provide an insight into the future development of new in vitro skin irritation tests.

Hen Egg Chorioallantoic Membrane Bioassay: An In Vitro Alternative to Draize Eye Irritation Test for Pesticide Screening

2008 ◽  
Vol 27 (6) ◽  
pp. 449-453 ◽  
Author(s):  
A. S. Kishore ◽  
P. A. Surekha ◽  
P. V. R. Sekhar ◽  
A. Srinivas ◽  
P. Balakrishna Murthy
Keyword(s):  
Chorioallantoic Membrane ◽  
Laboratory Animals ◽  
Test Compound ◽  
Eye Irritation ◽  
Test Chemical ◽  
Draize Test ◽  
Irritation Test ◽  
Hen Egg

As an alternative to the standard Draize eye irritation test, the potential irritancy of compounds was evaluated by observing adverse changes that occur in chorioallantoic membrane CAM) of the hen egg (HECAM) after exposure to a test chemical placed directly on the CAM. The occurrence of hemorrhage, coagulation, and lysis in response to a test compound is the basis for employing this technique to evaluate its potential for in vivo damage to mucous membrane, in particular the eye. Irritancy is scored according to the severity and speed at which damage occurs. In the present study, five different classes of pesticides were screened for irritation potential. There was good correlation between the HECAM assay and the in vivo Draize eye irritation test. The proposed HECAM assay, which reduces the requirement for laboratory animals, could be a painless alternative to the Draize test.

Recent Progress in the Eye Irritation Test

1993 ◽  
Vol 9 (6) ◽  
pp. 1017-1025 ◽  
Author(s):  
Ih Chu ◽  
Peter Toft
Keyword(s):  
Animal Studies ◽  
In Vitro Tests ◽  
Animal Testing ◽  
Regulatory Requirements ◽  
Eye Irritation ◽  
Significant Development ◽  
In Vivo Test ◽  
Irritation Test

The rabbit eye irritation test based on the Draize method is required for the hazard assessment of chemicals and products that may come into contact with the eye. Due to the potential for the suffering of animals and subjectivity of the test, many modifications of the method have been made that involved a reduction in the number of animals and a refinement of techniques. Additionally, there has been significant development of in vitro alternatives. This paper reviews recent advances in the in vivo test and in vitro alternatives, as well as regulatory requirements. While the refinement of in vivo protocols has resulted in a reduction in the number and discomfort on animals, the development of in vitro alternatives could lead to an eventual replacement of animal studies. In view of the inherent simplicity of many in vitro methods, some of which comprise cell cultures, further research into the relevance/mechanism of effects is required. Batteries of in vitro tests, when properly validated, may be considered as replacements for animal testing.

HET-CAM test for determining the possible eye irritancy of pesticides

2010 ◽  
Vol 58 (3) ◽  
pp. 369-377 ◽  
Author(s):  
Péter Budai ◽  
József Lehel ◽  
Judit Tavaszi ◽  
Éva Kormos
Keyword(s):  
Screening Method ◽  
Chorioallantoic Membrane ◽  
Alternative Methods ◽  
Eye Irritation ◽  
Parallel Data ◽  
Hen’S Egg ◽  
Irritation Test ◽  
Veterinary Products

Agrochemicals and veterinary products must undergo numerous toxicological tests before registration. The use of animals in these studies is a controversial issue. The Draize eye irritation test is one of the most criticised methods because of the injuries inflicted on the test animals. Several in vitro methods have been used to investigate the toxicity of potential eye irritants with a view to replacing in vivo eye irritation testing. One of these alternative methods is the Hen’s Egg Test — Chorioallantoic Membrane (HET-CAM) test. In the present studies comparative screening was performed with a set of agrochemicals to establish parallel data on in vitro (HET-CAM) and in vivo (Draize) results. The examined materials were: Totril (ioxynil), Omite 57 E (propargit), Actellic 50 EC (pyrimiphos-methyl), Stomp 330 EC (pendimethalin), Mospilan 3 EC (acetamiprid), Alirox 80 EC (EPTC), Match 050 EC (lufenuron), Nonit (dioctyl sulphosuccinate sodium), Perenal (haloxyfop-R methyl ester), Pyrinex 48 EC (chlorpyrifos). These experiments showed good correlation between results obtained by the HET-CAM test and those of the Draize rabbit eye test in most cases. The present form of the HET-CAM test can be proposed as a pre-screening method for the determination of eye irritative potential, therefore the number of test animals can be reduced and/or experimental animals can be replaced.

scholarly journals Evaluation of Eye Irritation Potential of Aqueous Leaf Extract of Achyranthes aspera by In Vitro and In Vivo Method

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Gajanan Rajpal Deshmukh ◽  
Kuntrapakam Hema Kumar ◽  
Poojari Venkata Suresh Reddy ◽  
Boddapati Srinivasa Rao ◽  
Chirumamilla Venkata Satish Kumar
Keyword(s):  
Leaf Extract ◽  
Chorioallantoic Membrane ◽  
Negative Control ◽  
Eye Irritation ◽  
Achyranthes Aspera ◽  
Hen’S Egg ◽  
Irritation Test ◽  
Aqueous Leaf Extract

The present paper is an attempt to investigate the eye irritation potential of aqueous leaf extract of Achyranthes aspera by in vitro, Hen's Egg Chorioallantoic Membrane Test (HET-CAM) and in vivo acute eye irritation test in rabbits. The irritation score (IS) obtained after treatment of the extract on HET-CAM is 0.07 and that of in rabbits is 0.55, Which does not comes under either category 1 or 2 as per the harmonized integrated classification system. The aqueous extract of Achyranthes aspera showed no eye irritation properties both in vitro and in vivo methods when compared with negative control whereas positive controls showed eye irritation potential.

An evaluation of five potential alternatives in vitro to the rabbit eye irritation test in vivo

1992 ◽  
Vol 6 (4) ◽  
pp. 275-284 ◽  
Author(s):  
D.M. Bagley ◽  
L.H. Bruner ◽  
O. de Silva ◽  
M. Cottin ◽  
K.A.F. O'Brien ◽  
...  
Keyword(s):  
Eye Irritation ◽  
Rabbit Eye ◽  
Irritation Test

scholarly journals State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products

2020 ◽  
Vol 4 ◽  
pp. 239784732097975
Author(s):  
Stéphanie Boué ◽  
Didier Goedertier ◽  
Julia Hoeng ◽  
Anita Iskandar ◽  
Arkadiusz K Kuczaj ◽  
...  
Keyword(s):  
Ad Hoc ◽  
State Of The Art ◽  
Physicochemical Characterization ◽  
Objective Evaluation ◽  
Vapor Generation ◽  
Characterization Methods ◽  
Clinical Exposure ◽  
Aerosol Generation

E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.

Three-dimensional Growth of Renal Epithelial Cells in Vitro: A Tool in Toxicity Testing

1993 ◽  
Vol 21 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Knut-Jan Andersen ◽  
Erik Ilsø Christensen ◽  
Hogne Vik
Keyword(s):  
Epithelial Cells ◽  
Three Dimensional ◽  
Toxicity Testing ◽  
Renal Tissue ◽  
Epithelial Cell Line ◽  
Multicellular Spheroids ◽  
Renal Epithelial Cell ◽  
Renal Epithelial Cells

The tissue culture of multicellular spheroids from the renal epithelial cell line LLC-PK1 (proximal tubule) is described. This represents a biological system of intermediate complexity between renal tissue in vivo and simple monolayer cultures. The multicellular structures, which show many similarities to kidney tubules in vivo, including a vectorial water transport, should prove useful for studying the potential nephrotoxicity of drugs and chemicals in vitro. In addition, the propagation of renal epithelial cells as multicellular spheroids in serum-free culture may provide information on the release of specific biological parameters, which may be suppressed or masked in serum-supplemented media.

Application of the EYTEX™ System to the Evaluation of Cosmetic Products and their Ingredients

1992 ◽  
Vol 20 (1) ◽  
pp. 146-163
Author(s):  
Francis H. Kruszewski ◽  
Laura H. Hearn ◽  
Kyle T. Smith ◽  
Janice J. Teal ◽  
Virginia C. Gordon ◽  
...  
Keyword(s):  
Double Blind ◽  
Eye Irritation ◽  
Ocular Irritation ◽  
Rabbit Eye ◽  
Wide Range ◽  
High Concentrations ◽  
Alkaline Membrane ◽  
Positive Agreement

465 cosmetic product formulations and raw ingredients were evaluated with the EYTEX™ system to determine the potential of this in vitro alternative for identifying eye irritation potential. The EYTEX™ system is a non-animal, biochemical procedure developed by Ropak Laboratories, Irvine, CA, that was designed to approximate the Draize rabbit eye irritation assay for the evaluation of ocular irritation. Avon Products Inc. provided all the test samples, which included over 30 different product types and represented a wide range of eye irritancy. All the EYTEX™ protocols available at the time of this study were used. Samples were evaluated double-blind with both the membrane partition assay (MPA) and the rapid membrane assay (RMA). When appropriate, the standard assay (STD) and the alkaline membrane assay (AMA) were used, as well as specific, documented protocol modifications. EYTEX™ results were correlated with rabbit eye irritation data which was obtained from the historical records of Avon Products Inc. A positive agreement of EYTEX™ results with the in vivo assay was demonstrated by an overall concordance of 80%. The assay error was 20%, of which 18% was due to an overestimation of sample irritancy (false positives) and 2% was attributed to underestimation (false negatives). Overestimation error in this study was due in part to the inability of the protocols to accurately classify test samples with very low irritation potential. Underestimation of sample irritancy was generally associated with ethoxylated materials and high concentrations of specific types of surfactants. 100% sensitivity and 85% predictability were described by the data, indicating the efficiency of EYTEX™ in identifying known irritants. A specificity rate of 39% showed the EYTEX™ assay to be weak in discerning non-irritants. However, the EYTEX™ protocols used in this study were not designed to identify non-irritants. A compatibility rate of 99% proved the effectiveness of the EYTEX™ assay in accommodating a diversity of product types. The EYTEX™ system protocols, when used appropriately, can provide a conservative means of assessing the irritant potential of most cosmetic formulations and their ingredients.

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

Sign in / Sign up

Export Citation Format

Share Document