Chemicals—Test method of in vitro skin corrosion—Transcutaneous electrical resistance test(TER)
Some standard content:
ICS 13.300;11.100
National Standard of the People's Republic of China
GB/T27828—2011
Chemicals
In vitro skin corrosion
Transcutaneous electrical resistance test method
Chemicals-Test method of in vitro skin corrosionTranscutaneous electrical resistance test(TER)2011-12-30 Issued
General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China Administration of Standardization of the People's Republic of China
Implementation on August 1, 2012
This standard was drafted according to the rules given in GB/T1.1—2009.
GB/T 27828-—2011
This standard is consistent with the technical content of OECD Chemical Testing Guide No. 430 (2001) "In Vitro Skin Corrosion: Transcutaneous Resistance Test Method" (English version). This standard has made the following structural and editorial changes: - Added a chapter on scope;
- Merged the "Introduction" section of QECD No. 430: 2004 into the "Introduction" section; - Removed the "For definitions in this guide, see Appendix" in the "Introduction" section of OECD No. 430: 2001; - Merged the "Initial Considerations" section of OECD No. 430: 2004 into the "Introduction" section; - Merged the "Appendix: Definitions" chapter of OECD No. 430: 2004 into the "Terms and Definitions" section; - Changed the measurement units to the legal measurement units of my country. This standard was proposed and coordinated by the National Technical Committee for Standardization of Hazardous Chemicals Management (SAC/TC251). The drafting units of this standard are: Occupational Health and Poison Control Institute of China Center for Disease Control and Prevention, Ningbo Institute of Inspection and Quarantine Science and Technology, China Institute of Inspection and Quarantine Science, and China Chemical Economic Development Center. The main drafters of this standard are Hou Fenjia, Ma Zhongchun, Ci Ke, Lin Jing, Yang Ting, Chen Xiaoken, Long Zaihao, and Lin Zhenxing. GB/T 27828—2011
Skin corrosion refers to the irreversible skin tissue damage caused by skin contact with the test substance [see the definition in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)]. This standard provides a test method for evaluating skin corrosion without using live animals. Skin corrosion tests usually require the use of experimental animals [\]. In the 2002 revision of the ()ECD Chemical Testing Guide 404 and its supplement, it was considered that this test method may cause pain and harm to experimental animals. Therefore, it is considered to change to an in vitro skin corrosion test method to avoid the pain and harm caused to experimental animals. The main difficulty in completely replacing the in vivo skin corrosion test (OECD 404) on animals is that there is no formal, independent, and validated in vitro corrosion test method. The first step in establishing an alternative skin corrosion test method should be to conduct a pre-validation test before the method is eliminated3), and then a formal in vitro skin corrosion test method validation study can be conducted [68]. Based on the results of the above-mentioned tests and other relevant literature, it is believed that the human skin model test (OECD431) and the transcutaneous resistance test method (ie, this standard) can be used to evaluate in vivo skin corrosion 9-11].
The results of the validation test and other published research data show that the rat transcutaneous resistance test method (TER test) [12-13] can reliably identify known skin corrosives and non-skin corrosives [5,91. This test can be used to identify the corrosiveness of chemicals and their mixtures. In addition, based on available information (e.g. pH, structure-activity relationships, human and/or animal data) and through a balance of evidence analysis, this standard can also be used to identify the non-corrosiveness of chemicals and their mixtures [1-2.11.14]. This standard does not generally provide information on skin irritation of the test substances, nor can it further classify corrosive substances according to the GHS rules! 1!
In order to fully evaluate the local effects of the test substances on the skin after a single percutaneous exposure, a sequential testing strategy is recommended (see OECD 401F2 and GHSC1). This testing strategy includes conducting in vitro skin corrosion tests and in vitro skin irritation tests first, and then considering the use of live animals for testing.
1 Scope
In vitro skin corrosion of chemicals
Transcutaneous resistance test method
GB/T 27828—2011
This standard specifies the terms and definitions, test principles, test methods, test data and reports for in vitro skin corrosion percutaneous electrical test methods for chemicals.
This standard applies to the in vitro skin corrosion test for transcutaneous electrical resistance. 2 Terms and definitions
The following terms and definitions apply to this document. 2.1
Skin corrosion in vivo Irreversible damage to the skin after 4 hours of contact with the test substance, that is, visible necrosis from the epidermis to the dermis. The characteristics of the corrosive effect are: ulceration, hemorrhage, bloody induration, and after 14 days, it manifests as skin atrophy and fading, local alopecia and induration. Suspected skin damage should be examined by histopathology.
Transcutaneous electrical resistance, TER The electrical resistance of the skin, expressed by resistance value (k2). The use of a Wheatstone bridge to record the permeability of the skin to ions is a simple and stable method for evaluating the barrier function of the skin. 3 Test principle
The test substance is applied to the surface of the epidermis placed in a two-layer test system for 24 hours. In this test system, the test skin between the layers can be used as an independent functional layer. The test skin was obtained from euthanized rats aged 28 to 30 days. The corrosiveness of the test substance was determined based on the degree of loss of the stratum corneum and the reduction of the skin barrier function (TER below the threshold) [121]. The results of rat TER tests on large chemicals showed that most TER values were much higher than 5ka (usually greater than 10kQ) or lower than 5k (usually less than 3kQ). Therefore, the TER threshold for determining whether rat skin was corrosive was set at 5kα [1a]. Generally, for substances that are non-corrosive to the skin of living animals, regardless of whether they are irritating or not, the measured TER value is generally not less than 5k. In addition, when using different skin or different test devices, the TER threshold may change, in which case further verification is required. A staining method is added to this test procedure to confirm positive results (including when the TER value is close to 5kQ). If the stratum corneum is damaged, the permeability of ions will increase, which can be verified by the staining method. There is evidence that the TFR test using rat skin can measure the results of the rabbit in vivo corrosion test (OECD4042). It should be noted that the results of the skin corrosion and skin irritation tests conducted by domestic rabbits are highly consistent with the results of human skin patch tests [15]. 4 Test methods
4.1 Experimental animals
Research has shown that rat skin is more sensitive to chemicals, so rat skin was selected for the test. The age and strain of the rats used are very important to ensure that the skin of the rats used for the test is in the dormant stage of hair follicles before hair growth begins. Wistar rats (or other similar species) about 22 days old are selected, both males and females are acceptable. Use small scissors to carefully trim the hair on the back and flank of the rats. Then wipe the animals carefully. At the same time, apply antibiotic solution (such as a solution containing effective concentrations of streptomycin, penicillin, chloramphenicol and amphotericin to inhibit bacterial growth) to the infected area, and wash the animals again with antibiotic solution after 3 to 4 days. If the cuticle has returned to normal after shearing, the animals can be used for the test within 3 days after the second washing. 4.2 Preparation of test skin
Euthanize the rats when they are 28 to 30 days old (this age is very critical). Remove the dorsal skin of each animal and carefully remove the excess subcutaneous fat to prepare a test skin with a diameter of about 20 mm. The test skin can be stored in an appropriate manner for future use, because the results of human experiments have shown that the data of the positive control and negative control of the test skin after storage are the same as those obtained with fresh skin.
Place the test skin at one end of a polytetrafluoroethylene (PTFE) tube, and make the epidermal surface of the skin face the PTFE tube and contact it. Then use the "O\" rubber ring to press and fix the test skin to the bottom of the PTFE tube, and cut off the excess skin. The specifications of the PTFE tube and the "O\" rubber ring (see A.1 in Appendix A), use vaseline to seal the "O\" rubber ring and the PTFE tube end. Use a spring wire clamp to fix the PTFE shoots in a receiving tube filled with magnesium sulfate solution (154 mmol/L) (see B. 1) and immerse the test skin at the lower end of the PTFE arm completely in the magnesium sulfate solution. 10 to 15 test skins can be prepared from the skin of each rat. Before the start of the test, take two pieces of test skin prepared from each animal for resistance measurement for quality control. The resistance of these two test skins must be greater than 10k2 before the remaining test skin can be used for testing. If it is lower than 10ka, the test skin made from the skin of this animal cannot be used for the test. 4.3 Toxicity of test substances and control substances
Positive and negative controls should be set up at the same time for each test to ensure that the test system is in a normal state. Test skin from the same animal should be used. It is recommended to use 10 for the positive control. mol/L hydrochloric acid, and distilled water was used for negative control. During the test, 150μL of liquid test substance was evenly applied to the surface of the test skin in the PTFE tube. If the test substance is solid, sufficient test substance should be added and evenly spread on the test skin to ensure that the entire surface of the outer skin is covered, and then 150μI. deionized water was added to the surface of the solid test substance and the arm was gently shaken to mix: In order to achieve the most effective contact between the solid test substance and the skin, the test substance should be heated to 30°C to melt or soften it, or the test substance should be ground into a fine powder. During the test, 3 test skins should be used for each test group and control group. The test substance should be exposed to the skin at 20 ℃ ~ 23 ℃ for 24 hours. After 14 hours, rinse the test object on the test skin with 30℃ water. 4.4 TER determination
Use a low voltage AC Wheatstone bridge to measure the skin impedance, namely TER (transcutaneous resistance) (3]. Usually the working voltage of the Wheatstone bridge is 1 V to 3 V, the frequency of the sine wave or triangle Wheatstone bridge AC power is 50 Hz to 1 000 Hz, and the measuring range is at least 0.1kn to 30k2. When the bridge used in the verification test has a frequency of 100Hz1000HIz (can be connected in series or in parallel), its inductance, capacitance and resistance should be able to reach the upper limits of 2 000H, 2 000μF and 2M respectively. When conducting TER corrosion determination, the measurement result is based on a ratio of 100 Hz, the resistance value under the condition of clean connection. Before measuring the resistance, apply a sufficient amount of 70% alcohol on the test skin to reduce the surface tension of the skin. After a few seconds, remove the alcohol and add 3L of 154mmol/l. magnesium sulfate solution to hydrate the skin tissue. Place the electrodes of the bridge on both sides of the test skin and measure the resistance value (kQ/test skin) (see B.1 in Appendix B). The diameter of the electrode and the length of the electrode below the optical distance of the crocodile mouth clip are shown in Figure A, 1. During the resistance measurement, the fish mouth clip holding the inner electrode should be covered on the top end of the PTFE tube to ensure that the length of the electrode immersed in the magnesium sulfate solution remains unchanged. Insert the outer electrode into the bottom of the receiving tube. The distance between the elastic paper clip on the PTFE tube and the bottom should remain unchanged (see A.1 in Appendix A), because this distance will affect the measured resistance value. Therefore, the distance between the inner electrode and the test skin should also remain unchanged and be as short as possible (1mm~2mm). 2
GB/T27828-—2011
If the measured resistance value is greater than 20k2, it may be due to the presence of the test substance on the test skin. The residual test substance should be further removed. For example, the PTFE tube can be blocked with a gloved thumb, shaken for about 10s, the magnesium sulfate solution in the tube is discarded and fresh magnesium sulfate solution is added before measuring the resistance again. The performance of the test device and the test procedure used can affect the TER value. The 5kα critical value for judging corrosiveness is only applicable to the determination of the TER value measured under the test device and test procedure conditions required by this method. If the test conditions are changed or a different test device is used, a different reading can be selected. Therefore, it is necessary to select a series of reference substances from the chemical substances L4-5 used for verification of the test or from substances similar to the test substance to conduct the test, so as to correct the test method and resistance reading. Some recommended suitable chemicals are shown in Appendix C.
4.5 Staining method
Some non-corrosive substances can reduce the TER value to below the critical value of 5k because these substances allow ions to pass through the stratum corneum and thus reduce the resistance 5. For example, neutral organic matter and surface-active chemicals (including detergents, emulsifiers and other surfactants) can remove lipids from the skin and increase the ion permeability of the skin. Therefore, if the TER value of the test substance is lower than or close to 5k but there is no visible skin damage, the control group and the poisoned group should be subjected to dye penetration tests to determine whether the reduction in TER value is caused by increased skin permeability or skin corrosion (3.5). Since the latter often causes damage to the skin stratum corneum, when rhodamine B sulfate dye is added to the skin surface, the dye will quickly penetrate the skin stratum corneum and stain the underlying skin tissue. This dye is stable to many chemicals. It is fixed and will not be affected by subsequent extraction tests. 4.6 Application and removal of rhodamine B sulfate dye 4.6.1 After determining TER, remove the magnesium sulfate solution and carefully inspect the skin for obvious damage. If no obvious damage is observed, add 150μL of a 10% (mass/volume) aqueous solution of rhodamine B sulfate (Acid Red 52; CI45100; CAS No. 3520-42-1) to the test skin and let it act for 2 hours. Then rinse the epidermis with tap water at least at room temperature for about 10 seconds to remove excess or unbound dye. 4.6.2 Carefully remove the test skin from the PTFE tube and place it in a bottle containing 8mL of deionized water (e.g. 20 mL glass scintillation vial) and gently shake for 5tmin to remove excess or unbound dye. After repeating the above cleaning steps, transfer the test skin to a bottle containing 5mL of 30% (mass/volume) sodium dodecyl sulfate (SDS) distilled water solution and incubate at 60℃ overnight. 4.6.3 After incubation, remove the test skin and discard it. Centrifuge the remaining solution at 21℃ for 8min (relative centrifugal force is 175g), aspirate 1imI. of the supernatant and dilute it to 5 times the original volume with 30% SDS solution, and measure the optical density (D) of the solution at 565nm. 4.7 Calculation of dye content
The D value can be used to calculate the amount of rhodamine B sulfate dye in each test skin. The content of the material [57 (the molar extinction coefficient of Rhodamine B sulfate dye at 565nm is 8.7×10°; the relative molecular mass is 580). Use an appropriate standard curve to obtain the dye content of each test skin, and calculate the average content of the dye in each test skin based on the repeated measurement values (parallel measurement values). 4.8 Interpretation of results
4.8.1 If the TER measurement values of the positive control and the negative control are within the range required in Table 1, the test results can be considered reliable. Table 1 Impedance range
Control Newton
10tnol/L Hydrochloric acid
Steamed stuffing water
Resistance range/kn
GB/T 27828—2011
4.8.2 If the amount of dye in the positive control and negative control combined with the test skin is within the range required by Table 2, the test results are considered to be reliable.
Table 2 Dye amount range
Control group
10mol/L hydrochloric acid
Distilled water
The test substance is considered to be non-corrosive to the skin if the following conditions are met4.8.3
The average TER of the test substance is greater than 5k; or a)
b) The average TER is less than or equal to 5kn and the test skin is not significantly damaged|and the dye content range/(\g/test skin) 40~100
The average dye content of the test skin is lower than the average dye content of the 10o1/L hydrochloric acid positive control (see 4.8.2).
4.8.4 The test substance is considered to be corrosive to the skin if the following conditions are met: a) the mean TER of the test substance is less than or equal to 5 kΩ and the skin is obviously damaged; or b) the mean TER is less than or equal to 5 kΩ and the test skin is not obviously damaged: but the mean dye content of the test skin is greater than or equal to the mean dye content of the 10 μl/1 hydrochloric acid positive control (see the positive control value in 4.8.2).
5 Test data and report
5.1 Data
List the resistance value (K) and the mean dye content of the test skin (\/test skin) of the test substance group, positive control group and negative control group in the form of a table (single test data and the mean of the parallel group), and each measured value and the mean of the repeated measurements should be listed. 5.2 Test Report
The test report should include the following information:
Test and control substances:
Chemical name (such as IUPAC or CAS name) and CAS; 2)
Content (mass fraction), purity and physical properties of the chemical substance or its preparation components; physicochemical properties (such as physical state, pH value, stability, water solubility); 3)
Pre-test treatment of the test and control substances (such as heating, grinding, etc.); 4)
Stability, if known, should be provided in the report). Experimental animals:
Animal strain and sex;
Animal age;
Animal source, breeding conditions and feed, etc.; details of skin preparation.
Test conditions,
Standard curve of the test system;
Standard curve of dye content determination;
Detailed test steps for TER measurement;
Detailed test steps for dye content determination (if necessary); Description of any modifications to the test procedure! 6
Criteria for judging corrosive effects.
Results:
GB/T27828—2011
A data table reporting the TER value and dye binding amount for each animal and each test skin in tabular form; 1)
Any symptoms observed.
Discussion.
Conclusion.
GB/T27828—2011
Appendix A
(Normative Appendix)
Schematic diagram of the dimensions of polytetrafluoroethylene (PTFE) tubes A. 1 Dimensions of polytetrafluoroethylene (PTFE) tubes (see Figure A.1). Spring wire selling
Figure A.1 Schematic diagram of the dimensions of polytetrafluoroethylene (PTFE) tubes (unit: millimeters)
Appendix B
(Normative Appendix)
Schematic diagram of the rat skin TER test apparatus
B.1 Schematic diagram of the rat skin TER test apparatus (see Figure B.1). Elastic porcelain wire clamp
Inner width shuttle (rent)
PTFE tube
Yellow fire
Receiving section
Magnesium phytate (154 mmbl/T, 1
"O\-type rubber ringbZxz.net
Magnesium magnetite (154mmal/L
Elastic wire clamp
External electrode (wire)
Test skin epidermis
Test skin dermis
Schematic diagram of mouse skin TER test equipment
GB/T 27828—20↑1
GB/T27828—2011
c.1 Table C.1 gives the corresponding reference substances. Chemical Name
1,2-Diaminopropane
Acrylic acid
2-tert-butylphenol
Potassium hydroxide (10%)
Sulfuric acid (10%)
Octanic acid (n-octanoic acid)
4-Amino 1,2,4 Triazole
Butyrol
Ethylbromopropene
Tetraethylene
Isostearic acid
4-Methylthiobenzaldehyde
Appendix C
(Informative Appendix)
Reference substances
Reference substances
Chemical Abstracts Service number
78-90-0
79-10-7
88-18-6
1310-58-3
7664-93-9
124-07-02
584-13-4
97-53-0
103-63-9
127-18-4
30399-84-9
3446-89-7
Severe corrosion
Severe corrosion
No corrosion
No corrosion
No corrosion
No corrosion
No corrosion
No corrosion
Corrosion degree
C,2 Most of the chemicals listed in Table C.1 are from the European Centre for Validation of Alternative Methods (the The list of chemicals selected by the Europcan Centre for the Validation of Alternative Methods (ECVAM) International Conformity Research Institute. The criteria for selecting the above substances are as follows:
Equal numbers of corrosive and non-corrosive substances, covering most chemical categories and chemical substances that can be obtained through commercial channels; including severely corrosive and slightly corrosive chemicals to ensure that the corrosive ability can be distinguished; the selected chemicals can be used normally in the laboratory except for their corrosiveness and have no other serious hazards. References
GB/T 27828--2011
[1] OECD (2001) Harmonised Integrated Classification System for Hutnan Health and Environmental Hazards of Chemical Substances and Mixtures. OECD Series an Testing and Assessment Number 33, ENV/JM/MONO (2001) 6, Parishttp://olis.occd.org/olis/2001doc.nef/L.inkTo/cnv-jn-mana(2001)6[2] OECD(2002).OECDGuideline forTesting of Chemicals.No.404:AcuteDermal Irritation,Corrasion,icviscd version,as adopted on 24 April 2002,7 Pp plus Anncx and Supplemcnt[ 3] Botham, PA, Chanberlain, M., Barratt, MD, Curren, RD, Esdaile, DJ, Gardner, JR., Gordon, VC, Hildebrand, B. Lewis, RW, Liebsch, M., Logemann, P., Osborne, R., Ponec.M., Regnier, JF, Steiling, W., Walker, AP, and Balls,M. (1995). A prevalidation study on in vitroskin corrosivity testing- The report and recommendations of ECVAM Workshop 6. ATLA 23,219-255[4] Barratt,MD,Brantom,PG,Fcntem,J.H,,Gerncr,I.,Walker,A,P.,and Worth,A,P.(1998). The ECVAM internatial validation study on in uztro tests far skin corrosivity. 1.Selectionand distribution of the test chemicals. Toxic. in Vitro 12,171-482[5]J Fentem, J. H. , Archer,G. E. B. , Balls, M. , Botham, P. A., Curren, R. D. , Earl, L. K. ,Esdaile,D.J.,Holzhitter,II.-G.and Licbsch,M.(1998).The ECVAMintetnational validation studyon in uitro tests for skin corrosivity. 2. Results and evaluation by the Managcment Team. Toxic. inVitro 12,483-524
[6] OECD(1996). Final Rcport of the OECD Workshop on Harmonizatian of Validation andAcceptance Criteria lor Alternative Toxicological Test Methods, 62pp[?] Balls,M.,Blaauboer,B.J.,Fentem,J.H.,Bruner, L,,Combes,R. D.,Ekwall,B.,Fielder.R.J. ,Guillouzo,A. , Lewis, R. W. , Lovell, D. P. , Reinhardt,C. A. , Repetto,G. ,Sladawski. D. ,Spiel-mann,H.,and Zucca,F, (1995).Practical aspects of the validation of toxicity test procedures. Thetecpart and rceammcndatians of FCVAM workshops. ATI.A 23,129-147[8] ICCVAM(Interagency Coordinating Cornmittee on the Validation af Alternative Methods).(1997). Validation and Regulatory Acceptance af Toxicological Test Methods, NIH Publication No.97-398l. National Institute of Environmental Health Sciences, Research Triangle Park , NC, USA.http://iccvam. niehs. nih. gav/docs/guidelines/validate. pdfE5] ECVAM(1998).ECVAM News & Views. ATLA 26,275-280E1oJ ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Meth-ods), (2002). ICCVAM evaluation of EpiDermTM ,EPISKINTM (EPI-200),and the Rat Skin Transcuta-neous Electrical Resistance (TER) assay: In Vitro test methods for assessing dermal corrusivitypotential of chemicals.NIH Publication No.02-4502.National Toxicology Prograrn Interagency Centerfor the Evaluation of Alternative Toxicological Methods, National Institute of Environmental HealthScienccs, Resecarch Triangle Park, NC, USA.http://iccvam. niehs. nih. gov/methods/epiddocs/epis_hrd. pdr[11] OECD(2002)Extended Expert Cansultatior Meeting on The In Vitro Skin Corrosion TestGuideline Proposal,Berlin, lst-2nd November 20ol,Secretariat' s Final Summary Report, 27t March2002,OECD ENV/EHS,available upon request from the SecretariatE12] Oliver,G. J. A. ,Pemberton, M. A. , and Rhodes,C. (1986). An in vitro skin corrosivitytest-nodifications and validation. Fd. Chem. Toxicol. 24, 5o7-5129Practical aspects of the validation of toxicity test procedures. Thetecpart and rceammcndatians of FCVAM workshops. ATI.A 23,129-147[8] ICCVAM(Interagency Coordinating Cornmittee on the Validation af Alternative Methods).(1997). Validation and Regulatory Acceptance af Toxicological Test Methods, NIH Publication No.97-398l. National Institute of Environmental Health Sciences, Research Triangle Park , NC, USA.http://iccvam. niehs. nih. gav/docs/guidelines/validate. pdfE5] ECVAM(1998).ECVAM News & Views. ATLA 26,275-280E1oJ ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Meth-ods), (2002). ICCVAM evaluation of EpiDermTM ,EPISKINTM (EPI-200),and the Rat Skin Transcuta-neous Electrical Resistance (TER) assay: In Vitro test methods for assessing dermal corrusivitypotential of chemicals.NIH Publication No.02-4502.National Toxicology Prograrn Interagency Centerfor the Evaluation of Alternative Toxicological Methods, National Institute of Environmental HealthScienccs, Resecarch Triangle Park, NC, USA.http://iccvam. niehs. nih. gov/methods/epiddocs/epis_hrd. pdr[11] OECD(2002)Extended Expert Cansultatior Meeting on The In Vitro Skin Corrosion TestGuideline Proposal,Berlin, lst-2nd November 20ol,Secretariat' s Final Summary Report, 27t March2002,OECD ENV/EHS,available upon request from the SecretariatE12] Oliver,G. J. A. ,Pemberton, M. A. , and Rhodes,C. (1986). An in vitro skin corrosivitytest-nodifications and validation. Fd. Chem. Toxicol. 24, 5o7-5129Practical aspects of the validation of toxicity test procedures. Thetecpart and rceammcndatians of FCVAM workshops. ATI.A 23,129-147[8] ICCVAM(Interagency Coordinating Cornmittee on the Validation af Alternative Methods).(1997). Validation and Regulatory Acceptance af Toxicological Test Methods, NIH Publication No.97-398l. National Institute of Environmental Health Sciences, Research Triangle Park , NC, USA.http://iccvam. niehs. nih. gav/docs/guidelines/validate. pdfE5] ECVAM(1998).ECVAM News & Views. ATLA 26,275-280E1oJ ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Meth-ods), (2002). ICCVAM evaluation of EpiDermTM ,EPISKINTM (EPI-200),and the Rat Skin Transcuta-neous Electrical Resistance (TER) assay: In Vitro test methods for assessing dermal corrusivitypotential of chemicals.NIH Publication No.02-4502.National Toxicology Prograrn Interagency Centerfor the Evaluation of Alternative Toxicological Methods, National Institute of Environmental HealthScienccs, Resecarch Triangle Park, NC, USA.http://iccvam. niehs. nih. gov/methods/epiddocs/epis_hrd. pdr[11] OECD(2002)Extended Expert Cansultatior Meeting on The In Vitro Skin Corrosion TestGuideline Proposal,Berlin, lst-2nd November 20ol,Secretariat' s Final Summary Report, 27t March2002,OECD ENV/EHS,available upon request from the SecretariatE12] Oliver,G. J. A. ,Pemberton, M. A. , and Rhodes,C. (1986). An in vitro skin corrosivitytest-nodifications and validation. Fd. Chem. Toxicol. 24, 5o7-5129
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