Developing a New Approach Methodology Framework to Assess Biological Responses to Nanoplastics: Insights from...

Area of Science:

• Environmental Health
• Nanotoxicology
• New Approach Methodologies (NAMs)

Background:

• Micro- and nanoplastics (MNPs) are pervasive environmental contaminants.
• Assessing MNP health risks requires advanced methodologies.
• New Approach Methodologies (NAMs) offer animal-free alternatives for hazard identification.

Purpose of the Study:

• To investigate the biological effects of polystyrene nanoplastics (PS-NPs) and polycaprolactone nanoplastics (PCL-NPs) using in vitro and in vivo models.
• To evaluate MNP-induced cytotoxicity, oxidative stress, DNA damage, cellular uptake, and barrier integrity.
• To assess transgenerational effects on oxidative stress and behavior in *Caenorhabditis elegans*.

Main Methods:

• Utilized advanced in vitro intestinal models and the 3R-compliant *Caenorhabditis elegans* model.
• Exposed models to varying concentrations of 100 nm and 20 nm PS-NPs and 100 nm PCL-NPs.
• Analyzed in vitro endpoints (cytotoxicity, oxidative stress, DNA damage, internalization, barrier integrity) and in vivo endpoints (oxidative stress, locomotor behavior across generations).

Main Results:

• PS-NPs induced significant in vitro DNA damage (≥50 µg/mL) and rapid cellular internalization, with 20 nm PS-NPs found in the nucleus.
• In vivo, PS-NPs increased oxidative stress and altered locomotor behavior across multiple generations in *C. elegans*.
• 100 nm PCL-NPs demonstrated weaker biological effects compared to PS-NPs, aligning with in vitro findings.

Conclusions:

• Integrated NAMs effectively assess biological impacts of MNP exposure.
• PS-NPs present a notable hazard, inducing DNA damage and transgenerational effects.
• Findings support the use of NAMs for evaluating MNP risks within a One Health framework.