In-vitro tiered approach alternative to live animal testing for determination of ocular or dermal irritation (An)

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

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PeBiToSens™: A Platform for PBT Screening of Fragrance Ingredients Without Animal Testing

CHIMIA International Journal for Chemistry ◽

10.2533/chimia.2020.168 ◽

2020 ◽

Vol 74 (3) ◽

pp. 168-175

Author(s):

Heike Laue ◽

Lu Hostettler ◽

Gordon Sanders ◽

Georg Kreutzer ◽

Andreas Natsch

Keyword(s):

The Body ◽

Trophic Levels ◽

Chemical Toxicity ◽

Animal Testing ◽

Ecotoxicological Assessment ◽

Microbial Biodegradation ◽

Animal Tests ◽

Safe By Design

The determination of persistence (P), bioaccumulation (B) and toxicity (T) plays a central role in the environmental assessment of chemicals. Persistence is typically evaluated via standard microbial biodegradation tests. Bioaccumulation refers to the accumulation of chemicals in organisms and is usually assessed in fish exposed to the test chemical. Toxicity is determined at three trophic levels, with fish toxicity as the highest trophic level assessed. Thus, animal tests are classically needed for both B and T assessment. In vitro systems based on fish liver cells or liver S9 fractions ('RT-S9 assay') have been recently adopted by OECD to measure the biotransformation rates for the chemicals for B assessment. Biotransformation drives clearance from the body and reduces bioaccumulation. For T assessment, an assay based on in vitro toxicity on fish gill cells has been established ('RTgill-W1 assay'). Here we summarize our findings indicating that these tests are highly predictive for fragrance ingredients, and show with two case studies of our latest new registered substances how we apply these tests in particular during development and also for chemical registration. This platform of tests (PeBiToSens™) could fully replace animal tests in ecotoxicological assessment and is key in the Givaudan Safe by Design™ approach to develop safer and environmentally compatible novel fragrance ingredients.

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Preparation and SPF Evaluation of Sunscreen Cream Containing Titanium Dioxide

VNU Journal of Science Medical and Pharmaceutical Sciences ◽

10.25073/2588-1132/vnumps.4153 ◽

2019 ◽

Vol 35 (1) ◽

Author(s):

Tran Thi Hai Yen ◽

Le Thu Huong ◽

Nguyen Thi Thanh Duyen ◽

Vu Thi Thu Giang

Keyword(s):

Titanium Dioxide ◽

Physical Stability ◽

Biological Evaluation ◽

Protection Factor ◽

Biomedical Analysis ◽

Protection Effect ◽

Dermal Irritation ◽

Oecd Guideline

Titanium dioxide, a physical sunscreen, is a metal oxide which reflects and disperses incident UV radiation by an optical mechanism. Sun protect factor (SPF) indicates the level of protection from UV rays. This study aims to prepare titanium dioxide sunscreen cream and evaluate its SPF. Sunscreen cream was first prepared by emulsification method, and then mixed with titanium dioxide. As a result, the sunscreen cream loaded with 5% titanium dioxide had good visual performance, physical stability, and medium UV protection effect with SPF 20+. Keywords Titanium dioxide, sunscreen, SPF. References [1] K. Morabito, N.C. Shapley, et al. Review of sunscreen and the emergence of non‐conventional absorbers and their applications in ultraviolet protection, International journal of cosmetic science. 33(5) (2011), 385-390. https://doi.org/10.1111/j.1468-2494.2011.00654.x.[2] Schalka Sergio, Reis Vitor Manoel Silva dos. Sun protection factor: meaning and controversies, Anais brasileiros de dermatologia. 86(3) (2011) 507-515. [3] Serpone Nick, Dondi Daniele, et al. Inorganic and organic UV filters: Their role and efficacy in sunscreens and suncare products, Inorganica Chimica Acta. 360(3) (2007) 794-802. https://doi.org/10.1016/j.ica.2005.12.057.[4] COLIPA. Method for in vitro determination of uva protection, (2011), 17-19.[5] Couteau Céline, Faure Aurélie, et al. Study of the photostability of 18 sunscreens in creams by measuring the SPF in vitro, Journal of pharmaceutical and biomedical analysis. 44(1) (2007) 270-273. https://doi.org/10.1016/j.jpba.2007.01.052.[6] ISO (2010), Biological evaluation of medical devices-Part 10: Tests for irritation and skin sensitization, 10.[7] OECD (2015), OECD Guideline for testing of chemicals: Acute Dermal Irritation/Corrosion, 404.

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Modern Approaches to Determination of the Biological Activity of Insulin and its

The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products ◽

10.30895/1991-2919-2019-9-2-85-92 ◽

2019 ◽

Vol 9 (2) ◽

pp. 85-92

Author(s):

T. A. Batuashvili ◽

L. V. Simutenko ◽

P. V. Shadrin ◽

N. P. Neugodova

Keyword(s):

Biological Activity ◽

Animal Models ◽

Insulin Analogues ◽

Quality Parameters ◽

The Body ◽

Animal Testing ◽

Biological Potency

The paper considers insulin’s specific action on the patient’s body, types of insulin preparations and insulin analogues which are used for the treatment of diabetes, as well as applicable requirements for these products. It was demonstrated that determination of biological activity is one of the key quality parameters of this type of medicines. The paper summarises the methods used for evaluation of insulin and its analogues, which are based both on the hormone’s general action on the body (in vivo: double crossing, euglycemic clamp, etc.), and on certain aspects of the hormone’s interaction with the body systems (in vitro: receptor-binding assay, phosphorylation, metabolic methods). Due to the appearance of insulin biosimilars on the pharmaceutical market, the article raises the issue that the «Biological potency» parameter tested in animals should be kept as part of the product specification. The analysis of the in vivo and in vitro methods of biological activity determination convincingly demonstrates that animal models can not be replaced with the modern analytical methods based on cell cultures. Consequently, animal models are still necessary, as they allow for an adequate assessment of the quality of insulins in terms of «Biological potency». Taking into account the global trend towards reduction of animal testing, the authors point out the need to develop modern methods, the results of which will be comparable to the results of in vivo determination of the biological activity.

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An Optimized MTT Bioassay for Determination of Cytotoxicity of Fumonisins in Turkey Lymphocytes

Journal of AOAC International ◽

10.1093/jaoac/77.2.512 ◽

1994 ◽

Vol 77 (2) ◽

pp. 512-516 ◽

Cited By ~ 18

Author(s):

Mary A Dombrink-Kurtzman ◽

Glenn A Bennett ◽

John L Richard

Keyword(s):

Gradient Centrifugation ◽

In Vitro Cytotoxicity ◽

Tetrazolium Salt ◽

Animal Testing ◽

Cytotoxicity Assays ◽

Cytoplasmic Vacuolization ◽

Diphenyl Tetrazolium Bromide ◽

Dose Dependent

Abstract In vitro cytotoxicity assays have been performed for detection and quantitation of fumonisins, as possible alternatives for whole animal testing. This study was undertaken to establish optimal in vitro conditions using turkey lymphocytes. Turkey lymphocytes were isolated from peripheral blood by Percoll gradient centrifugation. Cytotoxicity of fu-monisin B1 (FB1) and B2 (FB2) was determined by exposing lymphocytes to FB1 or FB2 at concentrations of 0.01–25 μg/mL for 24,48, or 72 h at 39°C. The MTT bioassay was used to measure cell viability and proliferation. In metabolically active cells, the tetrazolium salt, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], was reduced to MTT formazan. Turkey lymphocytes that had been exposed in vitro to FB1 and FB2 for 48 and 72 h showed inhibition of cell proliferation that was dose-dependent. The 50% inhibitory dose for FB1 and FB2 was 0.4–5 μg/mL. Cells exposed to FB1 or FB2 exhibited high levels of cytoplasmic vacuolization and were unable to proliferate, whereas proliferation of control lymphocytes was observed at 48 and 72 h. FB2 was 3- to 4-fold more cytotoxic than FB1.

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USEPA Efforts in Harmonization of Acute Toxicity Test Guidelines with OECD

Journal of the American College of Toxicology ◽

10.3109/10915819209141863 ◽

1992 ◽

Vol 11 (3) ◽

pp. 285-291 ◽

Cited By ~ 1

Author(s):

Mary C. Henry

Keyword(s):

Pollution Prevention ◽

Screening Methods ◽

Animal Testing ◽

Oral Toxicity ◽

Dermal Irritation ◽

Structure Activity ◽

Pain And Suffering ◽

Development And Validation ◽

Further Development

The USEPA, as a member of the OECD, is involved in the review of OECD guidelines and OECD's plans for revisions. The guidelines reviewed to date include: acute oral toxicity, eye and dermal irritation/corrosion, and skin sensitization. The revisions to the guidelines have emphasized reductions in animal usage in lab testing, and refinements which reduce/eliminate pain and suffering of animals. Screening methods, such as use of structure-activity relationships and physicochemical properties of test substances, which would eliminate chemicals that did not require animal testing, or sharply reduce the number of animals required for testing, were also recommended for some guidelines. In vitro methods were also examined as screens to eliminate severely toxic chemicals, but most of these methods still require further development and validation. The proposed revisions are discussed in detail in this report. This report has been reviewed by the Environmental Protection Agency's Office of Pollution Prevention and Toxics, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency.

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