In an article published on September 6, 2016 in the peer-reviewed journal PLoS One, Niels Hadrup and colleagues from the Technical University of Denmark evaluate the potential health effects that may result from a long-term exposure to a mixture of various chemicals at low concentrations.

The scientists designed a mixture containing 27 chemicals representative of environmental contaminants commonly detected in human urine or blood, such as metals, perfluorinated compounds, phthalates, phenols, pesticides, heterocyclic amines, polychlorinated biphenyls (PCBs), dioxins, polycyclic aromatic hydrocarbons (PAHs), and several others. This mixture was administered to juvenile male rats for three months via oral gavage once daily. The lowest dose was calculated to result in internal concentrations in rats similar to those observed in humans, and resulted in a combined dose of 27 chemicals equaling 0.16 mg/kg bw/day (designated Low-dose). Mid-dose and High-dose contained 0.47 and 1.6 mg/kg bw/day, respectively.

Body weight was not significantly affected by exposure to Low- or Mid-dose, but was approximately 20% lower in animals exposed to High-dose.

Relative liver weight was significantly increased in both the Low- and Mid-dose groups; this parameter was not assessed in the High-dose group. Histopathological changes of the liver were observed in all exposure groups, with both the type and severity of hepatocytic vacuolization showing dose-dependent increase and being significantly different from control starting from the lowest exposure dose. Statistically significant gene expression changes were also observed in the livers of Low- and Mid-dose exposed animals.

The Mid-dose exposure also resulted in a significant increase in the relative weight of kidney and spleen, but no significant changes were observed in the Low-dose group. In the High-dose group, this parameter was not assessed. Further, histopathological changes were observed in the kidneys of animals from Mid- and High-dose groups. Spleen histology was not assessed.

The plasma levels of four steroid hormones, androstenedione, testosterone, corticosterone, and progesterone, were not affected in the Low- or Mid-dose-exposed animals; the effects of High-dose exposure were not assessed.

Metabolomics analysis of blood samples showed a clear separation of control, Low- and Mid-dose groups, particularly for phospholipids, neutral lipids, and polar fraction metabolite categories. Combined with the significant liver toxicity observed in this study in response to even the lowest exposure dose, the authors argue that their data provide support to the hypothesis that the chemical burden could have contributed to the high incidence rate of hepatic steatosis observed in the U.S. (currently 20-40%).

Overall, their study delivers important experimental evidence demonstrating that “the combined environmental load of a large number of chemicals can pose a risk to the general population,” the authors conclude.


Hadrup, N., et al. (2016). “Juvenile male rats exposed to a low-dose mixture of twenty-seven environmental chemicals display adverse health effects.PLoS One 11(9): e0162027.