Non Targeted Screening And Risk Assessment Of Migrants In Food And Drug Contact Materials

Food and drug contact materials can protect food and drugs from physical,chemical and microbial factors.However,in the process of contact with food and drugs,small molecular substances in these contact materials will migrate to food and drugs,so it is necessary to conduct a risk assessment on food and drug contact materials to ensure that they will not endanger health.Based on Python technology,(Q)SAR toxicology evaluation software and access database software,the toxicology database of drug packaging extractables and leachables and the toxicology database of food packaging migration substances were developed.Based on the toxicology evaluation software,the toxicity grading evaluation strategy and risk matrix were developed.Non-targeted screening and risk assessment of non-volatile migration compounds in recycled polyethylene terephthalate(rPET)and paper straw were carried out.The results are as follows:(1)Through literature research,672 kinds of chemical substances in 16 articles related to extractables and leachables of pharmaceutical packaging materials were selected.The physicochemical and toxicological information was collected by using ChemSpider and PubChem database and three(Q)SAR software of toxtree,VEGA and T.E.S.T.Access was used to integrate toxicology database of extractables and leachables from drug packaging materials,and the screening process is changed from nontargeted to semi targeted by accurate mass number matching,which reduces the verification of multiple structures to be selected and speeds up the whole screening process.Taking the consistency evaluation of Ames mutagenicity endpoint by the above three evaluation software as an example,a toxicity grading evaluation strategy is proposed,which can quickly grade batches of unknown substances according to the toxicity evaluation results in the absence of experimental data.According to the number of positive/negative results of the three software,all substances were divided into five categories,and priority should be given to class ?substances.Among the 12 kinds of class ? toxic substances,8 were positive.(2)Through literature research,419 kinds of chemical substances in 44 pieces of literature related to food contact material migrants were selected.Python crawler technology was used to optimize the database establishment process,and the rapid establishment of a toxicology database of food contact material migrants was realized.Compared with TTC risk assessment for a small number of substances,a high-throughput TTC risk assessment method for a large number of substances was developed based on toxicology software such as ChemoTyper.In addition,combined with acute and chronic toxicology endpoints,water solubility and permeability,a risk matrix was developed to evaluate the safety of packaging materials,which can quickly classify the batch of unknown substances according to the degree of risk.419 kinds of migration substances were divided into four categories by risk matrix assessment,and 37 kinds of substances were classified as class ? risk substances,which should be given priority attention.(3)Non-targeted screening of non-volatile migrants/potential migrants in fragments,pellets,preforms and bottles of RPET was carried out by UPLC-Q-TOF-MS.a total of 48 substances were screened,including PET oligomers and polymer additives,most of which were PET oligomers.MS-DIAL was used for rapid screening of markers in different production stages of rPET products,and a total of 9 markers were screened.Based on the risk matrix,the risk assessment of migrants/potential migrants was carried out.The results showed that no class ? risk substances were found.Among class ? risk substances,the high risk substances mainly included PET oligomers with a molecular weight of about 500 Da.(4)Non-targeted screening of non-volatile migrants in two kinds of paper straw was carried out by UPLC-Q-TOF-MS.A total of 31 substances were screened,including adhesives,sizing agents,lubricants and antioxidants.The risk matrix was used to evaluate the risk of the migrants.The results showed that no class I risk substances were found.In class II risk substances,several adhesives and lubricants had a higher risk.