Presence of Polycyclic Aromatic Hydrocarbons in Rubber Packaging Materials and in Parenteral Formulations Stored in Bottles With Rubber Stoppers. 2017

Denise Bohrer, and Carine Viana, and Marcia M Barichello, and Juliane F de Moura, and Leandro M de Carvalho, and Paulo C Nascimento
1 Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Santa Maria, Brazil.

Rubber closures are the primary packaging material for sterile preparations intended for repeated use. Important features of rubber closures are achieved after additives are added to the elastomeric material that compounds the rubber. Among these additives is carbon black. Because of its origin, carbon black may contain polycyclic aromatic hydrocarbons (PAHs). The U.S. Environmental Protection Agency has identified 16 priority PAHs on the basis of concerns that they cause or might cause cancer in animals and humans. Regulatory agencies impose carbon black purity specifications based on limits for total PAHs (0.5 mg/kg) and benzo[a]pyrene (5 μg/kg) or benzo[a]pyrene only (250 μg/kg). PAHs in rubber packaging used for pharmaceutical formulations and in parenteral products stored in containers with rubber stoppers were investigated. To this end, the method proposed by the National Institute for Occupational Safety and Health-based on high-performance liquid chromatography with ultraviolet and fluorescence detection-was adapted to determine the levels of PAHs in rubber stoppers (gray and red) and in lipid emulsions and amino acid solutions stored in bottles with rubber stoppers. The rubber materials were shown to contain 12 PAHs, in concentrations ranging from 0.25-3.31 µg/g. Only 1 of 18 samples (11 amino acid solutions and 7 lipid emulsions) was uncontaminated. The most prevalent contaminants were pyrene, benzo[a]pyrene, and fluoranthene. The total PAH concentrations in the samples ranged from 0.11-5.96 µg/mL. Components of parenteral nutrition may be contaminated with PAHs, and rubber stoppers represent a potential source of these contaminants.

UI MeSH Term Description Entries
D011084 Polycyclic Aromatic Hydrocarbons Aromatic hydrocarbons that contain extended fused-ring structures. Polycyclic Aromatic Hydrocarbon,Polycyclic Hydrocarbons, Aromatic,Polynuclear Aromatic Hydrocarbon,Polynuclear Aromatic Hydrocarbons,Aromatic Hydrocarbon, Polycyclic,Aromatic Hydrocarbon, Polynuclear,Aromatic Hydrocarbons, Polycyclic,Aromatic Hydrocarbons, Polynuclear,Aromatic Polycyclic Hydrocarbons,Hydrocarbon, Polycyclic Aromatic,Hydrocarbon, Polynuclear Aromatic,Hydrocarbons, Aromatic Polycyclic,Hydrocarbons, Polycyclic Aromatic,Hydrocarbons, Polynuclear Aromatic
D011721 Pyrenes A group of condensed ring hydrocarbons.
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004340 Drug Contamination The presence of organisms, or any foreign material that makes a drug preparation impure. Drug Adulteration,Drug Contamination, Chemical,Drug Contamination, Microbial,Drug Contamination, Physical,Drug Impurity,Adulteration, Drug,Chemical Drug Contamination,Chemical Drug Contaminations,Contamination, Chemical Drug,Contamination, Drug,Contamination, Microbial Drug,Contamination, Physical Drug,Contaminations, Chemical Drug,Contaminations, Microbial Drug,Contaminations, Physical Drug,Drug Adulterations,Drug Contaminations,Drug Contaminations, Chemical,Drug Contaminations, Microbial,Drug Contaminations, Physical,Drug Impurities,Impurity, Drug,Microbial Drug Contamination,Microbial Drug Contaminations,Physical Drug Contamination,Physical Drug Contaminations
D005449 Fluorenes A family of diphenylenemethane derivatives.
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D012408 Rubber A high-molecular-weight polymeric elastomer derived from the milk juice (LATEX) of HEVEA brasiliensis and other trees and plants. It is a substance that can be stretched at room temperature to at least twice its original length and after releasing the stress, retract rapidly, and recover its original dimensions fully. Latex Rubber,Elastica,India Rubber,Natural Rubber,Plant Rubber,Vulcanite,Natural Rubbers,Plant Rubbers,Rubber, Natural,Rubber, Plant,Rubbers, Natural,Rubbers, Plant
D014481 United States A country in NORTH AMERICA between CANADA and MEXICO.
D014484 United States Environmental Protection Agency An agency in the Executive Branch of the Federal Government. It was created as an independent regulatory agency responsible for the implementation of federal laws designed to protect the environment. Its mission is to protect human health and the ENVIRONMENT. Environmental Protection Agency (U.S.),Environmental Protection Agency,Environmental Protection Agency, United States,USEPA
D015203 Reproducibility of Results The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results. Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face

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