Consumer Products Toxicological Safety Assessments
BioScreen offers safety assessment by a board certified toxicologist for any product type. Safety assessments are suitable for use in the following areas:
- EU registration
- Documenting product safety in lieu of clinical testing
- Adjuct to clinical testing
The Ames test is a biological assay to assess the mutagenic potential of chemical compounds A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen as cancer is often linked to mutation. However, a number of false-positives and false-negatives are known. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound since standard carcinogen assays on rodents are time-consuming (taking two to three years to complete) and expensive. The procedure is described in a series of papers from the early 1970s by Bruce Ames and his group at the University of California, Berkeley and work by Kristien Mortelmans at Stanford University.
Cytotoxicity assays are widely used by the pharmaceutical and medical industry to screen for cytotoxicity in compound libraries or devices that come into contact with blood or cells. Researchers can either look for cytotoxic compounds, if they are interested in developing a therapeutic that targets rapidly dividing cancer cells, for instance; or they can screen "hits" from initial high-throughput drug screens for unwanted cytotoxic effects before investing in their development as a pharmaceutical.
The Irritection Assay System is a standardized, quantitative in-vitro test method that can be employed to detect, rank, and predict the ocular and/or dermal irritation potential of cosmetics, consumer products, pharmaceuticals, and chemical raw materials.
Why Use the Irritection Assay System?
- The Irritection Assay System provides a reliable alternative to the traditional animal tests of ocular and/or dermal irritancy tests.
- The Irritection assays are quantitative and highly reproducible, thus allowing comparative ranking of samples and formulations with great accuracy.
- Prior studies have demonstrated that the Irritection assay results are highly correlated with those obtained in standard Draize tests.
Ocular Irritection Assays
The corneal irritancy of test materials is known to be related to their propensity to promote denaturation and disruption of corneal proteins. The Ocular Irritection Assay System is an in vitro test method that mimics these biochemical phenomena. This test consists of two essential components:
- A membrane disc that permits controlled delivery of the test material to a reagent solution and;
- A proprietary reagent solution that is composed of proteins, glycoproteins, lipids and low molecular weight components that self-associate to form a complex macromolecular matrix. Controlled mixing of the test material and the reagent solution during the assay incubation period promotes protein denaturation and disaggregation of the macromolecular matrix.
The changes in protein structure that are induced by the test material may be readily quantitated by measuring the resulting changes in turbidity (OD405) of the reagent solution.
Comparison of these optical density measurements to those produced by standard chemical irritants permits calculation of an "irritancy score" that has been shown to be directly related to the potential corneal irritancy of the test material.
Dermal Irritection Assays
Chemicals that cause dermal irritation are known to induce alterations in the structure of keratin, collagen and other dermal proteins. The Dermal Irritection Assay System is an in vitro test that mimics these biochemical phenomena.
This test also consists of two components:
- A membrane substrate that has been modified by covalently crosslinking a mixture of keratin, collagen and an indicator dye to it and;
- A reagent solution consisting of a highly organized globulin/protein macromolecular matrix.
Application of an irritant chemical to the membrane disc disrupts the ordered structure of keratin and collagen and results in release of the bound indicator dye. Additionally, dermal irritants induce changes in conformation in the globular proteins found in the reagent solution.
The extent of dye release and protein denaturation may be quantitated by measuring the changes in optical density of the reagent solution at 450 nm (OD450).
Comparison of these optical density measurements to those produced by standard chemical irritants permits calculation of an "irritancy score" that has been shown to be directly related to the potential dermal irritancy of the test material.
Optisafe in vitro Ocular Irritation AssayTM
The OptiSafeTM in vitro ocular irritation test is a standardized and quantitative acute ocular irritation test method that can be used to determine the irritation potential of cosmetics, creams, shampoos, toiletries, cleaning agents and a wide variety of consumer products.
Why Use the the OptiSafe in vitro Ocular Irritation Test?
Animal testing of cosmetics and personal care products is discouraged in the U.S. and banned in Europe. The E.U. requires non animal safety testing and the FDA requires safety testing or a warning within the Principal Display Panel (PDP) that the product has not been tested. Since ocular non-irritants are also dermal non- irritants, OptiSafeTM is the best choice for single test screening. OptiSafeTM can be used for:
- Satisfaction of FDA labeling requirements
- Due diligence to test whether the product is safe
- Product longevity: products that irritate do not last long in the marketplace
- The product to be tested is applied to a semi-permeable membrane (”ocular membrane") which is a material developed to be similar to the layer of tissue on the outside of the cornea.
- When the sample moves through the ocular membrane, it contacts a macromolecular matrix. This matrix has one component that issimilar in structure and organization to macromolecules within the cornea and a second component that predicts damage to molecules related to the immune response and cell viability.
- Irritants induce a change in the optical density (measured with a spectrophotometer).
- The level of opacity and damage to specific molecules has been found to predict the sample’s irritation potential.
The Advantages of OptiSafeTM include:
- High Accuracy Ocular Irritancy Test
- High Sensitivity for Mild and Moderate Irritants
- Low Cost
- Fast Results (standard 5 day turnaround time)
- Neither uses nor harms animals
- Satisfies minimal labeling requirements for Cosmetics, Personal Care and other Consumer Products.
The OptiSafeTM in vitro Assay Method has demonstrated value as a screening tool for a broad variety of consumer products.
HET-CAM Severe Ocular Irritation and Corrosion Assay
Early stage fertile hens eggs are used to determine if a substance is a severe ocular irritant or corrosive. Effects are measured by the onset of (1) hemorrhage; (2) coagulation; and (3) vessel lysis. The method followed is as described: NIH publication No. 10-7553- Published 2010: HET-CAM IS(A). Because early stage eggs are used this test is considered a non-animal test. This test can be used as a compliment to OptiSafeTM or as a standalone test to determine if a product is a severe ocular Irritant/corrosive.
Coming Soon (please inquire)
3T3 Neutral Red Uptake (3T3 NRU) Cytotoxicity Assay for the Identification of Substances not Requiring Classification for Acute Oral Toxicity
in vitro Dermal Irritation
- Uses differentiated Human Skin Tissue grown in culture
- Product to be tested is applied to differentiated Human tissue and cell viability is measured compared to the EpiskinTM , EpidermTM and SkinEthicTM test methods.
- Anti-aging claims substantiation can be measured at the same time (see below).
- Available February 2014
Human Stress and Toxicity Profile
- Provides information about how living skin cells respond (at the genetic level) to a product or formulation
- Uses differentiated Human Skin Tissue grown in culture and real time PCR.
- Measures the activity of over 80 genes involved in the stress response
- See below for a complete list of genes monitored and relevance.
- Available May 1 2014
Anti-Aging claims substantiation (I.E. Human Stress and Toxicity Profile Challenge Assay )
- Formulation, cream, lotion, makeup or other personal care product applied to differentiated Human Skin Tissue
- Measures changes in viability and the cellular genetic response after environmental challenges associated with aging (Ultraviolet Light and Oxidizing agents).
- Reports include specific genetic information and an overall anti-aging effectiveness score.
Additional info on human stress panel:
Human Stress and Toxicity Profile (Differentiated Human Skin) http://www.qiagen.com/Products/Catalog/Assay-Technologies/Real-Time-PCR-and-RT-PCR-Reagents/RT2-Profiler-PCR-Arrays?catno=PAHS-003Z#geneglobe
Functional Gene Grouping
Oxidative Stress: FTH1, GCLC, GCLM, GSR, GSTP1, HMOX1, NQO1, PRDX1, SQSTM1, TXN, TXNRD1.
Hypoxia: ADM, ARNT, BNIP3L, CA9, EPO, HMOX1, LDHA, MMP9 (Gelatinase B), SERPINE1 (PAI-1), SLC2A1, VEGFA.
Osmotic Stress: AKR1B1, AQP1, AQP2, AQP4, CFTR, EDN1, HSPA4L, NFAT5, SLC5A3.
Apoptosis: CASP1 (ICE), FAS, MCL1, TNFRSF10A, TNFRSF10B (DR5), TNFRSF1A.
Autophagy: ATG5, ATG7, ATG12, BECN1, FAS, ULK1.
Necrosis: FAS (TNFRSF6), GRB2, PARP1 (ADPRT1), PVR, RIPK1, TNFRSF10A, TNFRSF1A, TXNL4B.
Inflammatory Response: CCL2 (MCP-1), CD40LG (TNFSF5), CRP, IFNG, IL1A, IL1B, IL6, IL8, TLR4, TNF.
DNA Damage Signaling:
Cell Cycle Checkpoint/Arrest: CDKN1A (p21CIP1/WAF1), CHEK1, CHEK2 (RAD53), DDIT3 (GADD153/CHOP), HUS1, MRE11A, NBN (NBS1), RAD17, RAD9A.
Other Responses: ATM, ATR, DDB2, GADD45A, GADD45G, RAD51, TP53, XPC.
Heat Shock Proteins/Unfolded Protein Response: ATF4, ATF6, ATF6B, BBC3, BID, CALR, DDIT3, DNAJC3, HSP90AA1, HSP90B1 (TRA1), HSPA4 (HSP70), HSPA5 (GRP78).
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