Developmental toxicity assessment of common excipients using a stem cell-based in vitro morphogenesis model

Area of Science:

• Toxicology
• Developmental Biology
• Pharmacology

Background:

• Excipients in medications, foods, and cosmetics can pose developmental toxicity risks.
• Concentrations causing adverse effects on embryo development are largely unknown for most excipients.
• Assessing developmental toxicity is crucial for public health and safety.

Purpose of the Study:

• To determine the lowest observed adverse effect level (LOAEL) for developmental toxicity of common excipients.
• To investigate the impact of specific coloring agents and preservatives on embryonic development.
• To provide a novel in vitro approach for assessing excipient developmental toxicity.

Main Methods:

• Utilized a stem cell-based in vitro morphogenesis model using embryoid bodies (EBs).
• Assessed developmental toxicity by observing EB morphogenesis and recapitulation of embryonic processes.
• Performed gene expression analyses to identify molecular mechanisms of toxicity.

Main Results:

• LOAELs for EB morphogenesis impairment were established for six excipients.
• Methylparaben (200 μM), butylated hydroxyanisole (400 μM), allura red (600 μM), brilliant blue (600 μM), and metabisulfite (1000 μM) showed varying toxicity levels.
• Butylated hydroxyanisole and methylparaben significantly altered gene expression of developmental regulators.

Conclusions:

• The study identified LOAELs for developmental toxicity of several common excipients.
• The in vitro EB model effectively assesses excipient-induced developmental toxicity.
• Mechanistic insights into developmental toxicity of butylated hydroxyanisole and methylparaben were gained.