Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay

Kimura, Yutaka; Fujimura, Chizu; Ito, Yumiko; Takahashi, Toshiya; Terui, H.; Aiba, Setsuya

doi:10.1007/s00204-018-2199-7

Cited by 17 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lymphocytic and myeloid cells can be isolated from peripheral blood mononuclear cells (PBMCs) and can be tested to determine toxicity to each of these lineages specifically, upon chemical exposures ( Hassan et al, 2007 ; Pessina and Bonomi, 2007 ). Other targeted functional assays for specific mechanisms include human lymphocyte activation (HuLA) assay, an antigen recall assay, similar to the in vivo T-cell-dependent antibody response (TDAR) where multiple immune cell types are needed to produce responses; multiple cytokines (IL-2, IFN-γ, IL-1β, and IL-8) assay; and the BioMap panel of assays where test systems are constructed with one or more primary cell types from normal human donors stimulated with cytokines or growth factors recapitulate relevant signalling networks that naturally occur in human tissue or disease states and can be explored for specific biomarker readouts ( Collinge et al, 2010 ; Kimura et al, 2018 ; Singer et al, 2019 ; Collinge et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

et al. 2022

View full text Add to dashboard Cite

New Approach Methodologies (NAMs) promise to offer a unique opportunity to enable human-relevant safety decisions to be made without the need for animal testing in the context of exposure-driven Next Generation Risk Assessment (NGRA). Protecting human health against the potential effects a chemical may have on embryo-foetal development and/or aspects of reproductive biology using NGRA is particularly challenging. These are not single endpoint or health effects and risk assessments have traditionally relied on data from Developmental and Reproductive Toxicity (DART) tests in animals. There are numerous Adverse Outcome Pathways (AOPs) that can lead to DART, which means defining and developing strict testing strategies for every AOP, to predict apical outcomes, is neither a tenable goal nor a necessity to ensure NAM-based safety assessments are fit-for-purpose. Instead, a pragmatic approach is needed that uses the available knowledge and data to ensure NAM-based exposure-led safety assessments are sufficiently protective. To this end, the mechanistic and biological coverage of existing NAMs for DART were assessed and gaps to be addressed were identified, allowing the development of an approach that relies on generating data relevant to the overall mechanisms involved in human reproduction and embryo-foetal development. Using the knowledge of cellular processes and signalling pathways underlying the key stages in reproduction and development, we have developed a broad outline of endpoints informative of DART. When the existing NAMs were compared against this outline to determine whether they provide comprehensive coverage when integrated in a framework, we found them to generally cover the reproductive and developmental processes underlying the traditionally evaluated apical endpoint studies. The application of this safety assessment framework is illustrated using an exposure-led case study.

show abstract

Section: Discussionmentioning

confidence: 99%

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Thus, a lack of metabolic capacity does not seem to be a main cause of false-negative results. Also, the OECD-adopted in vitro assays also have limited metabolic capacity, but most pre/ prohaptens are correctly identified by the assays (Nukada et al, 2012(Nukada et al, , 2013Emter et al, 2010;Piroird et al, 2015;Takahashi et al, 2011;Kimura et al, 2015Kimura et al, , 2018Patlewicz et al, 2016). However, improving the metabolic capacity by adding rat liver S9 fractions to the KeratinoSens assay or by coculture of HaCaT keratinocytes with THP-1 in the h-CLAT increased the response to some pre/prohaptens tested (Hennen et al, 2011;Cao et al, 2012;Natsch and Haupt, 2013).…”

Section: The Dose-effect Relationship Of Cd69 Expression and Cell Viabilitymentioning

confidence: 99%

Performance of a novel in vitro assay for skin sensitization based on activation of T lymphocytes

Hou

Xing

et al. 2020

ALTEX

View full text Add to dashboard Cite

three of the four AOP KEs (OECD, 2015a(OECD, ,b, 2018. However, the OECD has not formally adopted any in vitro assay representing the fourth KE yet. In addition, it is consistently argued that a single in vitro assay for skin sensitization is not sufficient to substitute testing in an animal model (e.g., the LLNA). Instead, combination of in vitro methods into integrated approaches to testing and assessment (IATA) will be required (

show abstract

“…The precise procedure of the mIL-8 Luc was described in our previous publication (Kimura et al, 2018) and the OECD test guideline (OECD, 2018). Briefly, to dissolve chemicals, X-VIVO TM 15, a commercially available serum-free medium (Lonza, 04-418Q), was added to 20 mg of test chemical (regardless of the chemical's solubility) in a microcentrifuge tube, brought to a volume of 1 mL, vortexed vigorously and then shaken on a rotor at a maximum speed of 8 rpm for 30 min.…”

Section: Test Chemicals and Chemical Treatmentmentioning

confidence: 99%

The performance of an <i>in vitro</i> skin sensitisation test, IL-8 Luc assay (OECD442E), and the integrated approach with direct peptide reactive assay (DPRA)

et al. 2018

Self Cite

View full text Add to dashboard Cite

In all current in vitro skin sensitisation assays, DMSO is used to dissolve water-insoluble chemicals. However, our previous study suggested the superiority of the modified IL-8 Luc assay (mIL-8 Luc), in which X-VIVO TM 15 is used to dissolve chemicals, over the original assay using DMSO (oIL-8 Luc). In this study, to confirm the superiority of the mIL-8 Luc, we first increased the number of chemicals examined and demonstrated the superiority of the mIL-8 Luc, in which the mIL-8 Luc provided 87.6% of sensitivity, 74.2% of specificity, and 84.6% of accuracy. Next, to clarify the cause of false negative judgment by the mIL-8 Luc, we examined the effects of physical properties of chemicals on judgment. The results demonstrated that high molecular weight, high LogKo/w, or poor water solubility, did not cause false negative judgment. When it was accepted as an OECD test guideline, the criteria of the mIL-8 Luc to determine sensitisers were modified to further decrease false negative judgment by poor solubility. By applying the new criteria, the test guideline IL-8 Luc assay (tgIL-8 Luc) improved sensitivity but decreased specificity and increased the number of chemicals that cannot be judged. To overcome this problem, we examined a simple combination of the tgIL-8 Luc with direct peptide reactive assay (DPRA), which could improve specificity and decrease the number of the chemicals that cannot be judged. These data suggest that the tgIL-8 Luc is a promising in vitro skin sensitisation assay in combination with other in vitro or in chemico methods.

show abstract

Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay

Cited by 17 publications

References 12 publications

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

Performance of a novel in vitro assay for skin sensitization based on activation of T lymphocytes

The performance of an <i>in vitro</i> skin sensitisation test, IL-8 Luc assay (OECD442E), and the integrated approach with direct peptide reactive assay (DPRA)

Contact Info

Product

Resources

About