SIMPLE PHYSICOCHEMICAL PROPERTIES AS EFFECTIVE FILTERS FOR RISK ESTIMATION OF DRUGS AND ENVIRONMENTAL POLLUTANTS TRANSPORT INTO HUMAN BREAST MILK

摘要

For many decades serious concerns have been raised by the international scientific committee regarding the presence of drugs and environmental pollutant contaminants in human breast milk. In this aspect, milk/plasma concentration (M/P) ratio is considered as a crucial parameter for neonatal exposure, determining the extent of transport of drugs and environmental pollutants into human breast milk. In this aspect, the present study is aimed to assess whether simple physicochemical properties could be used as effective filters for risk estimation of drugs and environmental pollutants transport into human breast milk. In view of the above, a large data set of 350 structurally diverse drugs, bioactive food ingredients and environmental pollutants with literature available experimental M/P data was compiled and explored with respect to well recognized physicochemical properties. Compounds with M/P value >1 are considered to be present in human breast milk at higher levels than in maternal plasma, being classified as high risk compounds, while those with M/P <1 were classified as low risk compounds. By the use of the above cut-off point, 67% of the compounds were classified as low and the remaining 33% as high risk compounds among the whole data set as far as concern their extent to be transferred into human breast milk. High risk compounds were significantly characterized by increased lipophilicity compare to low risk ones (p<0.05). Enhanced polarity was significantly more frequently observed in low risk compared to high risk compounds (p<0.001). A significantly increased incidence of high risk compounds presented positive charge at pH 7.4 due to their basic properties (p<0.001). In contrast, negative charge at pH 7.4 related to acidic properties was significantly more frequently observed in the subgroup of low risk compounds (p<0.001). Enhanced flexibility and molecular size, expressed by the number of rotatable bonds included in the chemical structure and molecular weight, respectively, were significantly more frequently observed in low compared to high risk compounds (p<0.05). In conclusion, the present study supported substantial evidence by the use of a large data set of structurally diverse xenobiotic compounds that simple physicochemical properties related with lipophilicity, polarity and ionization could be used as adequate effective filters for risk estimation of drugs and environmental pollutants transport into human breast milk for which non experimental M/P data are currently available.