Developing context appropriate toxicity testing approaches using new alternative methods (NAMs)

Andersen, Melvin E.; McMullen, Patrick D.; Phillips, Martin B.; Yoon, Miyoung; Pendse, Salil N.; Clewell, Harvey J.; Hartman, Jessica K.; Moreau, Marjory; Becker, Richard A.; Clewell, Rebecca A.

doi:10.14573/altex.1906261

“…Several theoretical frameworks describing a tiered approach for NGRA have been published over the past few years ( Andersen et al , 2019 ; Berggren et al , 2017 ; Thomas et al , 2019 ), but concrete NGRA examples of how to analyze, integrate and interpret all the data obtained from NAMs to inform a safety decision are still lacking. Therefore, this work represents a milestone in the development and application of nonanimal approaches to assess human safety, showing for the first time that in chemico , in silico , and in vitro approaches can be integrated to arrive at a consumer safety decision for systemic effects.…”

Section: Discussionmentioning

confidence: 99%

A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

Baltazar

¹

,

Cable

²

,

Carmichael

³

et al. 2020

Toxicological Sciences

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Abstract Next-Generation Risk Assessment is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates new approach methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in face cream and body lotion. For the purpose of evaluating the use of NAMs, existing animal and human data on coumarin were excluded. Internal concentrations (plasma Cmax) were estimated using a physiologically based kinetic model for dermally applied coumarin. Systemic toxicity was assessed using a battery of in vitro NAMs to identify points of departure (PoDs) for a variety of biological effects such as receptor-mediated and immunomodulatory effects (Eurofins SafetyScreen44 and BioMap Diversity 8 Panel, respectively), and general bioactivity (ToxCast data, an in vitro cell stress panel and high-throughput transcriptomics). In addition, in silico alerts for genotoxicity were followed up with the ToxTracker tool. The PoDs from the in vitro assays were plotted against the calculated in vivo exposure to calculate a margin of safety with associated uncertainty. The predicted Cmax values for face cream and body lotion were lower than all PoDs with margin of safety higher than 100. Furthermore, coumarin was not genotoxic, did not bind to any of the 44 receptors tested and did not show any immunomodulatory effects at consumer-relevant exposures. In conclusion, this case study demonstrated the value of integrating exposure science, computational modeling and in vitro bioactivity data, to reach a safety decision without animal data.

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“…The experimental work involved a consecutive, in vitro , longitudinal, and double-blinded study design. The decision criteria method was used for the present investigation ( Andersen et al, 2019 ; Bentz et al, 2013 ). Based on the results obtained in each experiment, it was decided to continue the trials only with those propolis that showed antibacterial activity, antibiofilm and were not cytotoxic to gingival fibroblasts.…”

Section: Methodsmentioning

confidence: 99%

Antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro oral biofilm

Gómez

¹

,

Jon

²

,

Torres

³

et al. 2021

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Background: Natural products with antibacterial potential have begun to be tested on biofilm models, bringing us closer to understanding the response generated by the complex microbial ecosystems of the oral cavity. The objective of this study was to evaluate the antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro biofilm of Streptococcus gordonii and Fusobacterium nucleatum. Methods: The experimental work involved a consecutive, in vitro, longitudinal, and double-blinded study design. Propolis samples were collected from 13 different regions of the Peruvian Andes. The disk diffusion method was used for the antimicrobial susceptibility test. The cytotoxic effect of propolis on human gingival fibroblasts was determined by cell viability method using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the effect of propolis on the biofilm was evaluated by confocal microscopy and polymerase chain reaction (PCR). Results: The 0.78 mg/mL and 1.563 mg/mL concentrations of the methanolic fraction of the chloroform residue of Oxapampa propolis showed effects on biofilm thickness and the copy numbers of the srtA gene of S. gordonii and the radD gene of F. nucleatum at 48 and 120 hours, and chromatography (UV, λ 280 nm) identified rhamnocitrin, isorhamnetin, apigenin, kaempferol, diosmetin, acacetin, glycerol, and chrysoeriol. Conclusions: Of the 13 propolis evaluated, it was found that only the methanolic fraction of Oxapampa propolis showed antibacterial and antibiofilm effects without causing damage to human gingival fibroblasts. Likewise, when evaluating the chemical composition of this fraction, eight flavonoids were identified.

show abstract

“…The experimental work involved a consecutive, in vitro, longitudinal, and double-blinded study design. The decision criteria method was used for the present investigation (Andersen et al, 2019;Bentz et al, 2013). Based on the results…”

Section: Methodsmentioning

confidence: 99%

Antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro oral biofilm

Gómez

¹

,

Jon

²

,

Torres

³

et al. 2021

View full text Add to dashboard Cite

Background: Natural products with antibacterial potential have begun to be tested on biofilm models, bringing us closer to understanding the response generated by the complex microbial ecosystems of the oral cavity. The objective of this study was to evaluate the antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro biofilm of Streptococcus gordonii and Fusobacterium nucleatum. Methods: The experimental work involved a consecutive, in vitro, longitudinal, and double-blinded study design. Propolis samples were collected from 13 different regions of the Peruvian Andes. The disk diffusion method was used for the antimicrobial susceptibility test. The cytotoxic effect of propolis on human gingival fibroblasts was determined by cell viability method using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the effect of propolis on the biofilm was evaluated by confocal microscopy and polymerase chain reaction (PCR). Results: The 0.78 mg/mL and 1.563 mg/mL concentrations of the methanolic fraction of the chloroform residue of Oxapampa propolis showed effects on biofilm thickness and the copy numbers of the srtA gene of S. gordonii and the radD gene of F. nucleatum at 48 and 120 hours, and chromatography (UV, λ 280 nm) identified rhamnocitrin, isorhamnetin, apigenin, kaempferol, diosmetin, acacetin, glycerol, and chrysoeriol. Conclusions: Of the 13 propolis evaluated, it was found that only the methanolic fraction of Oxapampa propolis showed antibacterial and antibiofilm effects without causing damage to human gingival fibroblasts. Likewise, when evaluating the chemical composition of this fraction, eight flavonoids were identified.

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Developing context appropriate toxicity testing approaches using new alternative methods (NAMs)

Cited by 32 publications

References 61 publications

A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

Antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro oral biofilm

Antibacterial, antibiofilm, and cytotoxic activities and chemical compositions of Peruvian propolis in an in vitro oral biofilm

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