Study of the incorporation mechanisms of organic chemicals into hair. (Doctoral thesis)

Hair presents several advantages for biomonitoring the exposure to pollutants. For instance, this matrix is representative of the mid to long term exposure depending on the length of the sample. However the question concerning the hair incorporation mechanism of chemicals remain partially unravelled.
The subject of the present PhD was the “study of the incorporation mechanisms of organic chemicals into hair” (StICHa). Therefore we focused on the influence of biological and physicochemical parameters on the incorporation of pesticides into hair.
The results presented in the project were obtained from three experiments whose two animal experiments conducted on rats. The first one allowed to link levels of exposure of pesticides to the corresponding concentrations in plasma and in hair. This also allowed to study the accumulation of pesticides in the rat body over time and to investigate the influence of the pesticide physicochemical properties on their incorporation into hair. The second one provided pharmacokinetic (PK) parameters of pesticides in blood after a single exposure and highlighted the concept of background exposure corresponding to the detectable chemicals concentration in the animals before exposure due to environmental contamination. An in vitro test was also conducted to investigate bonds between pesticides and blood components and their influence on hair incorporation.
Correlation study between plasma and hair concentration of pesticides demonstrated that adjusting the plasma concentration by Cmax significantly improved the association with concentration in hair (rpearson from 0.29 to 0.88). Correlation study between level of exposure and hair concentration highlighted that adjusting the level of exposure by MRT or T1/2 also significantly improved the association with concentration in hair (rearson from 0.50 to 0.78). Moreover, pesticides with long PK tended to accumulate in the body over time after a repeated exposure (illustrated by an increase of concentrations in hair). These results confirmed that PK was a crucial aspect for pesticide incorporation into hair. On the contrary, pesticide physicochemical properties did not influence their incorporation in hair from blood. Finally, the pesticide binding to blood component seemed influence by the compound itself and the blood composition.
The ultimate aim was to provide a theoretical model linking chemical “concentration in hair” to “level of exposure” that can be applied to any compounds. The model developed in the present thesis (adjusting by MRT or T1/2) was therefore tested on other compounds with data obtained from our lab or the literature. Two Polycyclic Aromatic Hydrocarbon metabolites and Ethylglucuronide, a metabolite of alcohol fitted with the model as the association was better after the adjustment. These promising results confirmed that the pharmacokinetic of chemicals played an important role in their incorporation into hair.