Monday, 29 June 2020 10:40

DNT: Mixtures can be more harmful than individual chemicals Featured

Using cell cultures and a mathematical model, scientists at the European Union's Joint Research Centre have found that the effects of chemical mixtures on the developing human brain can be more harmful than the sum of the individual chemical effects determined in tests.


The JRC team exposed human brain cells under development to individual chemicals as well as mixtures of such chemicals in concentrations actually found in human samples to simulate real exposure.

The research team used human pluripotent stem cell (hiPSC) derived neural precursor cells differentiated in mixed cultures of neurons and astrocytes. They then studied the chemical effects on synaptogenesis, neurite outgrowth and the content of brain-derived neurotrophic factor (BDNF) proteins in the neurons. The scientists used chemicals with similar and dissimilar mechanisms of action, but an identical key event of an adverse outcome pathway (AOP) leading to a developmental neurotoxic adverse event.

An AOP is the structured representation of a biological outcome along with one or more series of causally related key events (KE) between a molecular triggering event (MIE) and an adverse outcome (AO).

The JRC team found that chemicals of non-toxic concentrations in a mixture can have adverse effects on the development of human brain cells. The mixtures of chemicals significantly altered several cellular processes known to be indicators of developmental neurotoxicity (DNT), particularly those related to cognitive deficits in children.

The researchers concluded that so-called mixed effects can be greater than the effects caused by the strongest single chemical in a mixture because of their additive or, in some cases, even synergistic effect.

Original publication:
Pistollato, F., Mendoza de Gyves, E., Carpi, D., Bopp, S. K., Nunes, C. Worth. A. & Bal-Price, A. (2020). Assessment of Developmental Neurotoxicity Induced by Chemical Mixtures Using an Adverse Outcome Pathway Concept. Environ Health. 19/1: 23. doi: 10.1186/s12940-020-00578-x.

Source:
https://ec.europa.eu/jrc/en/science-update/effects-chemical-mixtures-developing-brain