A Statistical Basis for Using Fewer Rabbits in Dermal Irritation Testing

An acceptable and validated in vitro method to evaluate the potential of a chemical to cause dermal irritation does not exist; therefore, in vivo studies remain the only alternative. Currently most laboratories utilize 6 rabbits per test, but this group size may not be necessary to derive the desired information. Data generated from 6-rabbit skin irritation tests of 105 materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from 6 rabbits. There are 630, 1575, 2108, and 1575 possible combinations of 105 studies for the 5-, 4-, 3-, and 2-rabbit subseta, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score, Comparisons indicated that the 5-, 4-, 3-, and 2-rabbit scores were in 96, 94, 91, and 88% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2-rabbit scores versus the 6-rabbit Draize score were 0.996, 0.994, 0.986, and 0.977, respectively. This study indicated that 3 rabbits per test group allow for adequate assessment of the dermal irritation potential of a chemical. These results also conformed closely to those obtainetd from a previous statistical study using eye irritancy data from 155 chemicals, where 3-rabbit subsets were 94% predictive of the 6-rabbit tests.

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Further validation of an in vitro method to reduce the need for in vivo studies for measuring the absorption of chemicals through rat skin

Fundamental and Applied Toxicology ◽

10.1016/0272-0590(92)90085-v ◽

1992 ◽

Vol 19 (4) ◽

pp. 484-492 ◽

Cited By ~ 41

Author(s):

R SCOTT

Keyword(s):

In Vivo Studies ◽

Rat Skin ◽

In Vitro Method

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Caco-2 Cell Iron Uptake from Meat and Casein Digests Parallels in Vivo Studies: Use of a Novel in Vitro Method for Rapid Estimation of Iron Bioavailability

Journal of Nutrition ◽

10.1093/jn/126.1.332 ◽

1996 ◽

Vol 126 (1) ◽

pp. 332-339 ◽

Cited By ~ 111

Author(s):

Raymond P. Glahn ◽

Elizabeth M. Wien ◽

Darrell R. van Campen ◽

Dennis D. Miller

Keyword(s):

Iron Uptake ◽

Iron Bioavailability ◽

In Vivo Studies ◽

In Vitro Method ◽

Rapid Estimation

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Comparison of In Vivo (Draize Method) and In Vitro (Corrositex Assay) Dermal Corrosion Values for Selected Industrial Chemicals

International Journal of Toxicology ◽

10.1080/10915810305094 ◽

2003 ◽

Vol 22 (2) ◽

pp. 99-107 ◽

Cited By ~ 15

Author(s):

Jody L. Stobbe ◽

Kevin D. Drake ◽

Kurt J. Maier

Keyword(s):

Animal Studies ◽

Skin Irritation ◽

Worker Safety ◽

In Vitro Test ◽

Industrial Chemicals ◽

In Vivo Test ◽

End Point ◽

Dermal Irritation

Skin irritation is a common occupational hazard for employees engaged in the manufacture, transport, and use of industrial chemicals. The most common method used to evaluate dermal irritation and/or corrosion has typically been in vivo tests using rabbits (Draize method). Several in vitro test methods have been developed, with Corrositex being the first to gain approval by a regulatory agency (U.S. Department of Transportation). The purpose of this study was to compare the results of in vitro (Corrositex) assays of dermal irritation/corrosion to in vivo test data for several industrial chemical formulations and to determine the predictability and usefulness of the Corrositex assay for these types of products. Twenty-four (24) formulations were qualified, categorized, and evaluated using the Corrositex method and the results compared to available animal data for each of the formulations. The Corrositex assay accurately predicted a corrosive end point in 8 (57.1%) of the 14 formulations identified as corrosive by the in vivo evaluations. Corrositex accurately predicted a noncorrosive end point for 1 (10%) of 10 formulations determined to be noncorrosive in animal studies. The Corrositex assay overpredicted the packing group for 12 (50%) of the 24 formulations, and underpredicted the packing group for 7 (29.2%) of the 24 formulations. Compared to the in vivo results, Corrositex correctly classified as corrosive or noncorrosive 37.5% of the formulations tested. A concordance of 20.8% for the packing group assignments of the evaluated formulations was calculated. The Corrositex assay did not accurately predict a corrosive end point or packing group assignment for all of the formulations used in this study. Manufacturers should assess the relevance of this method to their products prior to relying on it for compliance with hazardous material and worker safety regulations.

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Further Validation of an in Vitro Method to Reduce the Need for in Vivo Studies for Measuring the Absorption of Chemicals through Rat Skin

Toxicological Sciences ◽

10.1093/toxsci/19.4.484 ◽

1992 ◽

Vol 19 (4) ◽

pp. 484-492

Author(s):

R. C. SCOTT ◽

P. L. BATTEN ◽

H. M. CLOWES ◽

B. K. JONES ◽

J. D. RAMSEY

Keyword(s):

In Vivo Studies ◽

Rat Skin ◽

In Vitro Method

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Influence of Porous Dressings Based on Butyric-Acetic Chitin Co-Polymer on Biological Processes In Vitro and In Vivo

Materials ◽

10.3390/ma12060970 ◽

2019 ◽

Vol 12 (6) ◽

pp. 970 ◽

Cited By ~ 2

Author(s):

Witold Sujka ◽

Zbigniew Draczynski ◽

Beata Kolesinska ◽

Ilona Latanska ◽

Zenon Jastrzebski ◽

...

Keyword(s):

Wound Healing ◽

Subcutaneous Tissue ◽

Biological Effects ◽

Skin Irritation ◽

Early Period ◽

In Vivo Studies ◽

Control Group ◽

Dressing Materials

In spite of intensively conducted research allowing for the development of more and more advanced wound dressing materials, there is still a need for dressings that stimulate not only reparative and regenerative processes, but also have a positive effect on infected and/or difficult-to-heal wounds. Porous dressing materials based on butyric-acetic chitin co-polyester containing 90% of butyryl and 10% of acetyl groups (BAC 90/10) can also be included in the group mentioned above. Two types of dressings were obtained by the salt leaching method, i.e. a porous sponge Medisorb R and Medisorb Ag with an antibacterial additive. The aim of the study was to evaluate biological effects of porous Medisorb R and Medisorb Ag dressings under in vitro and in vivo conditions. In an in vitro biodegradation test, no mass loss of Medisorb R dressing was observed within 14 days of incubation in physiological fluids at 37 °C. However, on the basis of the FTIR (Fourier Transform Infrared Spectroscopy) tests, surface degradation of Medisorb R dressing was observed. Additionally, the antibacterial activity of the porous Medisorb Ag dressing containing microsilver as an antibacterial additive was confirmed. The in vivo studies included inflammatory activity, skin irritation and sensitisation tests, as well an assessment of local effect after contact with subcutaneous tissue up to 6 months and skin wounds up to 21 days. In the in vivo tests, the dressings exhibited neither effects of skin irritation nor sensitisation. Under macroscopic examination, in full thickness defects of subcutaneous tissue and skin, the dressings caused wound healing with no inflammation, undergoing the most gradual biodegradation between weeks 4 and 8, and the observed differences were statistically significant. In the histological assessment, a weakened, limited inflammatory process associated with degradation of the material has been observed. The process of skin wound healing under Medisorb R dressing in the early period was accelerated compared to that observed in the control group with a gauze dressing.

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Review of skin irritation/corrosion hazards on the basis of human data: a regulatory perspective

Interdisciplinary Toxicology ◽

10.2478/v10102-012-0017-2 ◽

2012 ◽

Vol 5 (2) ◽

pp. 98-104 ◽

Cited By ~ 26

Author(s):

David Basketter ◽

Dagmar Jírova ◽

Helena Kandárová

Keyword(s):

Patch Test ◽

Skin Irritation ◽

Alternative Methods ◽

Test Protocol ◽

Rabbit Skin ◽

Irritation Test ◽

Skin Irritation Test

Abstract Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human. The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test. A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man.

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Allopurinol Loaded Transferosomes for the Alleviation of Symptomatic After-effects of Gout: An Account of Pharmaceutical Implications

Current Drug Therapy ◽

10.2174/1574885515666200120124214 ◽

2020 ◽

Vol 15 (4) ◽

pp. 404-419

Author(s):

Ruchi Tiwari ◽

Gaurav Tiwari ◽

Rachna Singh

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Ex Vivo ◽

Release Kinetics ◽

Skin Permeation ◽

Skin Irritation ◽

In Vivo Studies ◽

Transdermal Drug Delivery System

Background: The present study assessed the transdermal potential of transferosomes loaded with allopurinol for the treatment of gout. Methods: Transferosomes of allopurinol were composed of different ratios of tween-80, soya lecithin and solvent using a thin-film hydration method. Transferosomes were characterized for Scanning Electron Microscopy (SEM), zeta potential, % entrapment efficiency (%EE), Fourier Transform Infrared Spectroscopy (FTIR), in-vitro drug release and kinetics as well as stability. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, ex vivo skin permeation study, flux, and stability. Results: SEM studies suggested that vesicles were spherical and zeta potential were in the range of -11.4 mV to -29.6 mV and %EE was 52.4- 83.87%. FTIR study revealed that there was no interaction between allopurinol and excipients during the preparation of transferosomes. The cumulative percentage of drug release from various transferosomes was ranged from 51.87 to 81.87%. A transferosomal gel of F8 formulation was prepared using dispersion method reported pseudoplastic rheological behavior, optimum pH, spreadability and maximum drug permeation i.e. 79.84% with flux 13.06 g/cm2/hr, followed zero-order release kinetics. Irritation and in-vivo studies of optimized transferosomal gel G8 on rabbits revealed better results than the standard allopurinol. Conclusion: This research suggested that allopurinol loaded transferosomal gel can be potentially used as a transdermal drug delivery system for the treatment of gout.

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