Safety assessment for Tris(2,4-di-tert-butylphenyl) phosphite (Irgafos 168) used as an antioxidant and stabilizer in food contact applications.

During and after fabrication of polymeric food contact articles (FCA), polymers undergo oxidation by thermal decomposition processes initiated by oxygen, heat, light, shear, and catalyst residues. To reduce degradation of the polymer, a commonly used secondary antioxidant (AO), Irgafos 168 (I-168), may be included. Use of I-168 in polymeric FCAs presents a potential concern for neurotoxicity due to its phosphate-containing degradation species, I-168ate. As a result, we evaluated dietary exposure and oral toxicity data for I-168 and its degradants when used as an AO in FCAs. Our exposure assessment included extensive review of the U.S. food-contact regulatory history of I-168 resulting in a combined cumulative estimated daily intake (CEDI) of 0.09 mg/kg bw/day for I-168 and I-168ate when used as an AO in FCAs. Our comprehensive literature review of toxicological data and supporting structure activity relationship (SAR) analysis of I-168 reactivity against acetylcholinesterase diminished concern for potential neurotoxic effects of I-168 and its degradants. An acceptable daily intake (ADI) value of 1 mg/kg bw/day for I-168 was derived from a two-year rodent combined chronic toxicity/carcinogenicity study, which is higher than the CEDI and supports the safety of current authorized food contact use levels of I-168.

A review of dietary exposure and toxicological information on epoxidised soybean oil (ESBO) in food-contact applications.

Plasticisers have a long history of use in the industrial manufacture and processing of polymers for the purpose of increasing the flexibility and strength of the material. Approximately, 80-90% of the plasticiser market is devoted to the production of PVC, a highly versatile thermoplastic used to produce both rigid and flexible articles. Many types of plasticisers, including ortho-phthalate esters (OPE), can be added to PVC to impart flexibility. Recently, alternatives to OPEs, such as epoxy esters and aliphatic adipates, are becoming more prevalent for use in PVC-based food-contact articles. Epoxidised soybean oil (ESBO) is used as a plasticiser in flexible PVC for many food-contact articles, including food packaging and food processing equipment, from which it can potentially migrate into food and become a component of an individual's daily diet. The purpose of this review is to provide an update on the US dietary exposure and toxicological information on ESBO used in PVC-based food-contact articles. The cumulative dietary concentration (CDC) and cumulative estimated daily intake (CEDI) for ESBO from its use as a plasticiser in PVC-based food-contact articles (i.e. gaskets for glass jar lids and film wraps) was calculated to be 2.6 mg/kg (i.e. ppm) and 0.13 mg/kg bw/d, respectively, for the general population. Some regulatory agencies have reported safety levels for ESBO, and the most conservative no observed adverse effect level (NOAEL) was identified to be 100 mg/kg bw/d (i.e. 2000 ppm) based on a two-year feeding study in rats. The current CEDI is well below these levels, supporting the safe use of ESBO in food-contact applications.

Safety assessment for octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate (CAS Reg. No. 2082-79-3) from use in food contact applications.

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (CAS Reg. No. 2082-79-3), currently marketed as Irganox 1076 (I-76), is a sterically hindered phenolic antioxidant used in a variety of organic substrates, including those used in the manufacture of food contact articles. In 2012, the US Food and Drug Administration (USFDA), Office of Food Additive Safety (OFAS), initiated a post-market re-evaluation of the food contact applications of I-76. This project aimed to ensure that current dietary exposures from the use of I-76 in food contact articles are accurately captured and the safety assessment considered all relevant and available toxicological information. To accomplish these aims, the USFDA reviewed the available toxicological studies and chemistry information on food contact applications of I-76. Based on this in-depth analysis, a NOAEL of 64 mg/kg-bw/d (female rats) from a chronic rat study and a cumulative estimated dietary intake (CEDI) of 4.5 mg/p/d, was used to calculate a margin of exposure (MOE) of ∼850. We concluded that the previous and current exposure levels provide an adequate margin of safety (MOS) and remain protective of human health for the regulated uses.

Optimizing the Synthesis of Tetratellurafulvalene.

A systematic synthetic study of the pi-donor tetratellurafulvalene (TTeF, 6) has resulted in an optimized preparation producing repeatable yields of over 20%. The use of a "one-step" Li/Sn metal exchange/Te(0) insertion procedure and freshly prepared microcrystalline Te(0) serve to drive toward products, the equilibria converting (Z)-1,2-bis(trimethylstannyl)ethylene (1) to its corresponding metal-exchanged vinyllithium species and subsequently to lithium ditellurolate 5. Furthermore, the use of LiCl as an additive to enhance the reactivity of n-BuLi in these metal exchange reactions also increases yields and reproducibility. The slow addition of 1 equiv of tetrahaloethylene during the final cyclization step favors intramolecular reactions which produce TTeF vs intermolecular reactions that lead to oligomeric byproducts. The use of tetrabromoethylene in place of tetrachloroethylene in this step also reduces byproduct formation.

The use of structure-activity relationship analysis in the food contact notification program.

Food contact substances (FCS) include polymers, paper and paperboard, and substances used in their manufacture, that do not impart a technical effect on food. Moreover, FCSs are industrial chemicals generally consumed at dietary concentrations (DC) of less than 1mg/kg food (ppm), and more commonly at less than 0.05 ppm (50 ppb), in the daily diet. As such, many industrial chemicals have been analyzed for toxicological concern, some of which may share structural similarity with FCSs or their constituents, and the majority of these studies are available in the public domain. The DCs of these compounds lend themselves to using structure-activity relationship (SAR) analysis, as the available "expert systems" and use of analogs allows for prediction and management of potential carcinogens. This paper describes the newly implemented food contact notification (FCN) program, the program by which FDA reviews FCSs for safe use, the administrative review of FCSs, the SAR tools available to FDA, and qualitative and quantitative risk assessments using SAR analysis within the regulatory framework of reviewing the safety of FCSs.