Toxicology

In Vitro Toxicology – Toxvit™

Aragen supports a wide panel of in vitro toxicology assays conducted under GLP guidelines to minimize animal use and to provide a cost effective way for early assessment of compound safety. With a suite of modern, reliable and validated testing technologies and protocols, combined with large scale operations with high-throughput equipment, we can reduce testing times and control costs. Toxvit^TM enables decisions on human relevant dose levels and robust mechanistic data for the effective translations of assay results.

In Vitro Toxicity Solutions

Multi-Parametric Cytotoxicity

• IC50 determination
• Cell loss/death (fluorescent imaging)
• Nuclear size and morphology (fluorescent imaging)
• Cell membrane permeability (fluorescent imaging)
• ~50 different cell lines of human origin available for cytotoxicity testing

Genetic Toxicity

• AMES MPF assay using Xenometrix AG – ANIARA microplate kit method (OECD 471)
• In vitro micronucleus assay using CHO, CHL, A549 cell lines and human PBMCs including cytotoxicity assessment on high content screening (HCS) platform (OECD 487)
• In vitro chromosomal aberration assay using CHO cell line and human PBMCs including cytotoxicity assessment (OECD 473)
• Mammalian cell gene mutation assay: MLA (L5178YTk+/- cell line) and HPRT (CHO-K1 cell line) mutations (OECD 490/476)
• In vitro comet assay using PBMC, CHO, CHL test systems on HCS platform
• H2AX double strand DNA damage response assay using A549, HepG2 and BEAS-2B cell lines on HCS platform

Dermal Toxicity

• In vitro irritation using 3D reconstructed human epidermis models (OECD 439)
• In vitro skin corrosion using 3D reconstructed human epidermis models (OECD 431)
• Phototoxicity assay using BALB/c-3T3 cells
• Skin sensitization assay using KeratinoSens cell line (OECD 442D)
• Skin sensitization by directing peptide reactivity assay (OECD 442C)

Ocular Toxicity

• Short term exposure assay using corneal epithelial cells (Statens Seruminstitut Rabbit Cornea SIRC cell line) (OECD 491)
• EpiOcular™ eye irritation assay using 3D reconstructed human corneal epithelium tissue model (OECD 492)

Hepatotoxicity Panel

• Using HepG2, HUH7, Hep3B cell lines and human iPSC HepRG spheroid cultures
• Drug-induced phospholipidosis and steatosis
• Lysosomal trapping (lysosomotropism)
• Cholestasis
• Mitochondrial permeability transition

Cardio Toxicity

• hERG safety screening using Invitrogen’s Predictor™ hERG fluorescence polarization assay kit
• 3D microtissue-based cardiotoxicity assay using human iPSC – CM (cardiomyocytes) spheroid cultures

Mitochondrial Toxicity

• Mitochondrial (Glu/Gal) assay in glucose and galactose supplemented media
• Mitochondrial membrane potential and cytochrome release

Neuro Toxicity

• Developmental neurotoxicity
• Neurite outgrowth
• Synaptogenesis assay

Endocrine Disruption Screening

• Estrogen receptor and androgen receptor binding assays, using polar screen, human full-length ER (alpha/beta) competitor assay and polar green rat androgen receptor competitor assay
• Fluorescence polarization assay kits using ligand binding assays for ER and AR from rat membrane preparations (OPPTS/OCSPP 890.1250, OPPTS/OCSPP 890.1150)
• Steroidogenesis assay using H295R cell line with testosterone parameter assay kit and estradiol parameter assay kit (R&D systems) (OECD 456)
• Aromatase assay: (OPPTS/OCSPP 890.1200)

Toxicogenomic Profiling

• Toxicological gene regulation studies through relative and quantitative expression of metabolic and toxicological pathway regulatory biomarkers using RT PCR and NGS platforms

 Toxicity Testing Platforms

• High content imaging (thermo scientific cell insight) CX7 platform
• Multimode reader – Perkin Elmer Envision 2104 platform
• Flow cytometry – BD FACS verse platform
• Agilent platform for HPLC
• RT PCR – Applied Biosystems QuantStudio 6Flex platform
• Next generation sequencing (NGS) – Illumina platform

Toxicity Testing Technologies 

• Primary cell culture technology
• Pluripotent stem cell technology (PSC)
• 3D microtissue culture technology