Many epidemiological studies have shown that exposure to pesticides is a risk factor for human health, as evidenced by the positive correlation between professional exposure to these compounds and an increase in the incidence of various human diseases (reviewed in Merhi et al. [1
]). The general population is also exposed to pesticides mainly via food intake. Thus many people have a lifelong exposure to low doses of pesticides, the impact of which on human health is not yet known.
Organochlorine (OC) pesticides are among the most frequent contaminants found in the environmental compartments because they persist in the environment and bioaccumulate in organisms, partly due to their lipophilic properties [2
]. Endosulfan is a chlorinated cyclodiene pesticide which was first severely restricted then banned in 2006 in several European Union countries. Nevertheless, the general population continues to be exposed: like other persistent organochlorine pesticides, endosulfan residues have been detected in several foods including fruits, vegetables, and fish [3
]. There is an evidence that endosulfan is acutely poisonous to humans through both accidental and intentional exposure [4
Endosulfan is classified by the World Health Organisation as a moderately hazardous (class II) pesticide [5
]; however, it is genotoxic [6
] and is an endocrine disrupter displaying xenooestrogenic activity [7
]. Endosulfan has been shown to be toxic to the liver, kidney, nervous system, and reproductive organs of laboratory animals [8
]. Exposure to this compound can modify the activity of some enzymes involved in oxidative stress and xenobiotic metabolism, as well as testosterone metabolism and clearance [11
]. Recently Casabar et al. [12
] showed that endosulfan was a strong activator of the pregnane X receptor (PXR) and an inducer of cytochrome P450 (CYP) 2B6 and CYP3A4, so it may have an impact on the metabolism of their substrates. A recent study by Ozmen et al. [13
] showed that treating rabbits with endosulfan led to changes in glucose levels, histological degenerative changes in the pancreas and endocrine disturbances. Endosulfan may also be a risk factor for children whose parents have been exposed since the accumulation of organochlorine compounds in fat tissue during the mother's life can expose the child during pregnancy and breast feeding [2
]. The transfer of OC pesticides from mother to foetus was demonstrated via the detection of the pesticides in the maternal umbilical cord, placenta, and in samples taken from the newborn [2
]. Moreover, Pathak et al. [14
] suggested that levels of some organochlorine pesticides such as endosulfan in the maternal fluid or tissue are associated with preterm delivery and increased foetal oxidative stress. Pre- and postnatal exposure to endosulfan is reported to affect biogenic amines and amino acids in the prefrontal cortex [15
]. Whilst the toxicological effects of endosulfan have been studied in vitro
and in vivo
, the impact of long-term exposure to low doses through dietary intake in animal models from the foetal stage to adulthood has not yet been reported.
An NMR spectroscopy-based metabonomic approach coupled with pattern recognition technology is an effective way of characterizing the biochemical response of an organism to contaminant exposure and identifying potential biomarkers of exposure [16
]. Metabonomics has proven to be a very useful tool in investigating the biochemical effects of many toxic compounds [18
In our study we developed a mouse model of diet to assess the impact of dietary exposure to a low dose of endosulfan on metabolic homeostasis in mice exposed from foetal development until adult age. We investigated biomarkers of dietary exposure using an 1H-NMR-based metabonomic approach in various tissues and biofluids.