Study On Determination And Safety Assessment Of Perfluorooctane Sulfonate (PFOS) In Drug Packaging Materials

The safety of drug packaging materials is an important part of the drug safety. Perfluorooctane sulfonate (PFOS) is widely used in production of drug packaging materials, due to its non-hydrophilic and non-lipophilic properties. Recent research demonstrated that PFOS is toxic, bioaccumulative and persistent in the environment, and was listed as restricted substance by many countries and international organization. It is of great significance to determine the PFOS in packaging materials and to assess the ecological and health risk of PFOS.Accelerated solvent extraction technique was used to effectively extract PFOS with methanol from drug packaging materials, of which the parameters were optimized by response surface methodology. A silylation step was then carried out for the extract by adding N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA). The silylated PFOS were identified and quantified by gas chromatograph/mass (GC/MS). The test results showed that the line range is from 50.0 ng/mL to 0.5×103 ng/mL; the correlation coefficient is 0.9913; the low limit of detection (LOD) is 13.9 ng/mL; and the average recovery is 98.4%. The samples test results showed that the concentrations of PFOS in a kind of polytertfluoroethylene (PTFE) drug packaging materials is from 31.6 ng/g to 33.7 ng/g.The ultra proficiency liquid chromatograph-mass/mass (UPLC-MS/MS) method was also developed to determine the trace amount of PFOS in the drug packaging materials. The methanol was used to extract PFOS from the samples. After filtration and concentration, the extract was quantified by LC-MS/MS. The test results showed that the line range is from 0.5μg/mL to 1.0×102μg/mL; the correlation coefficient is 0.9996; the low limit of detection (LOD) is 1.0 ng/g, and the average recovery is between 88% - 105%. The samples test results showed that the concentration of PFOS in a kind of polytertfluoroethylene (PTFE) drug packaging materials is 34.1 ng/g, indicating that the similar determination result was obtained compared to GC/MS method.The acute toxicity, skin irritation / corrosion, reproductive toxicity and neurotoxicity of Perfluorooctanesulfonate (PFOS) were studied in this thesis. The resulted show that acute toxicity LD50 value of mice is 501 mg/kg. PFOS is classified as 4 type graded according to the document of"Globally Harmonized System of Classification and Labelling of Chemicals"(GHS). Results of acute inhalation toxicity test showed that PFOS does not belong to acute inhalation of toxic substances. LC50 value of aquatic acute toxicity (zebrafish) is 37.31 mg/L. In the GHS system, PFOS is aquatic toxicity substance type 3. Skin irritation/corrosion test results showed that PFOS is not irritation substance but minor irritant substance. Bone marrow micronucleus test results showed that PFOS induced micronuclei in mouse bone marrow cells elevated, which means PFOS has a certain degree of genetic toxicity. And the sperm abnormality test results also prompted that PFOS has potential damage effect on male reproductive cells. Finally the neurotoxicity test results indicated that PFOS has a direct toxic damage or other damages on the brain tissue with certain dose - response relationship.Based on the published data of PFOS levels from China and Asia coast areas as well as from the aquatic environment in the USA, ecological risk assessment (ERA) of PFOS was performed using hazard quotient method. The results showed that, for both China and Asia coast, the ecological risk index Q(f,c) is lower than 0.001, and the growth inhibition risk index Q(a) is lower than 0.003, of which the risk level is relatively low. The growth inhibition risk for selenastrum capricornutum and anabaena flosaquae is low. While for skeletonema costatum, the growth inhibition risk is moderate. For zebra fish, rainbow traut, sheepshead minnow and water flea, the ecological risk is low in America. And for bluegill sunfish, pimephales promelas, mysidopsis bahia and oyster, the ecological risk is moderate.Mathematical model was established and applied for human health risk assessment (HRA) of PFOS for China water area, Asia coastal area and USA water area. And the human lifetime excess risk index (R) is lower than 10-6 for both China water area and Asia coastal area, and is of low risk level. The human lifetime excess risk index (R) of some USA cities is between 10-6 and 10-4, and reaches the low risk level.