The chemical substances have been widely used worldwide for crop protection for a long time, which makes a great probability for humans to exposure to a plethora of different chemicals continuously and simultaneously via the environment and agricultural products. The compounds have inherent toxicities, and may accumulate in the human body that interacts with each other and, thus, trigger additional effects that may negatively impact health, such as development, reproduction, hepatotoxicity in humans.

Status quo of environmental chemical effect assessment

For regulatory purposes, plenty of single substances are analyzed in regards to toxicological risk assessment. Although the possible implications of mixture toxicities are long known, the experimental challenges of the toxicological tests of substance mixtures are substantial. Previously, the toxicological tests of substance mixtures have been described, for instance, studies on potential endocrine-disrupting chemicals or groundwater contaminants. However, because of the multitude of substances and even more possible combinations, it is hardly feasible to test substance interactions comprehensively in rodent bioassays, the current gold standard of toxicity testing.

In order to address the issue, many studies investigate the toxic effects of specific mixtures and several in vitro approaches have been proposed, such as potential endocrine-disrupting chemicals in in vitro systems. There also exists translating challenges between in vitro information and in vivo outcomes. Simultaneously, compared to whole organisms, the in vitro assays are absence of complexity, which is particularly needed to study the toxicodynamics and compensatory mechanisms. Lack of complexity in these mechanisms can lead to limit the predictivity and regulatory applicability of simple in vitro assays especially for complex endpoints and exposure scenarios. On another hand, since interactions of chemicals in respect to synergistic or antagonistic effects may not be confined to a common molecular target, a whole animal is needed. Consequently, alternative models and approaches to analyze the toxic effect of mixtures are urgently needed.

A promising model for analyses of possible mixture effects

As a laboratory model, C. elegans offers many experimental advantages, including its small size, transparency, rapid life cycle, large brood size, and simple culture with E. coli. Due to its small size and rapid life cycle, C. elegans can be easily cultured in multiwell plates that are similar to in vitro systems, and further for high-throughput (HT) screening. Despite consisting of a countable number of cells in adult hermaphrodites, the millimeter-long body of C. elegans contains multiple specialized tissues including neuromuscular, digestive and reproductive systems, which make it possible to investigate the complex substance interactions in a whole living system. Therefore, C. elegans not only represent the whole animal used in assay, but also are applied in in vitro methods. Thus, it can be used to bridge the intrinsic gap between in vitro and in vivo approaches. Additionally, C. elegans shares a large number of conserved genes and several signaling pathways with humans, which make it a powerful model system to identify toxicity relevant signaling pathways for humans. In total, despite a simple organism, C. elegans combines relevant advantages of complex in vivo and fast in vitro assays. C. elegans is a promising model for analyses and prediction of mixture effects and can contribute to identifying mixtures of concern for human health and environment.

CD BioSciences is dedicated to providing the best service to accelerate the achievement of our customers' research goals. As a biosensor for environmental toxicity monitoring. C. elegans can be used for investigating the toxic effect of chemical substances, especially for the chemical mixture. If you are interested in this area, please feel free to contact us.

Reference

1. Wittkowski P, et al. (2019). "Caenorhabditis elegans As a Promising Alternative Model for Environmental Chemical Mixture Effect Assessment-A Comparative Study". Environ Sci Technol. 53(21):12725-12733.

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