Mineral oil in food, cosmetic products, and in products regulated by other legislations.

For a few years, mineral oils and their potential adverse health effects have been a constant issue of concern in many regulatory areas such as food, cosmetics, other consumer products, and industrial chemicals. Analytically, two fractions can be distinguished: mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). This paper aims at assessing the bioaccumulative potential and associated histopathological effects of MOSH as well as the carcinogenic potential of MOAH for consumer-relevant mineral oils. It also covers the absorption, distribution, metabolism, and excretion of MOSH and MOAH upon oral and dermal exposures. The use and occurrence of consumer-relevant, highly refined mineral oils in food, cosmetics and medicinal products are summarized, and estimates for the exposure of consumers are provided. Also addressed are the challenges in characterizing the substance identity of mineral oil products under REACH. Evidence from more recent autopsy and biopsy studies, along with information on decreasing food contamination levels, indicates a low risk for adverse hepatic lesions that may arise from the retention of MOSH in the liver. With respect to MOAH, at present there is no indication of any carcinogenic effects in animals dermally or orally exposed to highly refined mineral oils and waxes. Such products are used not only in cosmetics but also in medicinal products and as additives in food contact materials. The safety of these mineral oil-containing products is thus indirectly documented by their prevalent and long-term use, with a simultaneous lack of clinical and epidemiological evidence for adverse health effects.

Towards the limiting of health risks associated with tattooing: whitelists for tattoo pigments and preservatives.

The number of pigments that could potentially be used in tattoo inks is vast. However, pigments are generally not manufactured for the purpose of being injected into subepidermal layers of the skin. Assuming 100% bioavailability after injection means that pigments can be imminently hazardous to human health. Given the ever-increasing number of pigments being circulated on the market or through the internet, a 'negative list' ('black' list) containing pigments with known adverse effects will never be finalised. If incriminated, substances could easily be replaced by structurally similar pigments that might be even more deleterious to human health. Therefore, we and others suggest the establishment of a whitelist ('positive list') that would only contain pigments that had undergone a risk assessment specifically for their application into the dermis. Some of the problems associated with such a 'positive list' are discussed. Another important issue with regard to tattoo safety is related to the preservatives used in ink preparations. Notwithstanding the demand for sterile tattoo inks, a whitelist for these compounds would be beneficial. At present, many technical preservatives are being used, despite their known detrimental effects to human health. Criteria for the inclusion of preservatives in a 'positive list' are also discussed.

Toxicologically relevant phthalates in food.

Various phthalates have been detected in a wide range of food products such as milk, dietary products, fat-enriched food, meat, fish, sea food, beverages, grains, and vegetables as well as in breast milk. Here we present an overview on toxicologically considerable phthalate levels in food reported in the literature. The most common phthalates detected are di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP). Milk analyses demonstrate that background levels in unprocessed milk are usually low. However, during processing the phthalate contents may significantly increase due to migration from plastic materials in contact with food. Among dietary products fat-enriched food such as cheese and cream were identified with highest levels of DEHP. Plasticized PVC from tubes, conveyor belts, or disposable gloves used in food processing is an important source for contamination of food, especially of fatty food. Paper and cardboard packaging made from recycled fibers are another important source of contamination. In addition, gaskets used in metal lids for glass jars have been identified as possible source for the contamination of foodstuffs with phthalates. The highest concentrations of DEHP reported (>900 mg kg(-1)) were detected in food of high fat content stored in such glass jars. Beyond classical food, DEHP and DnBP were identified in human breast milk samples as the main phthalate contaminants. Phthalate monoesters and some oxidative metabolites were also quantified in breast milk.

Physiologically based toxicokinetic modelling as a tool to assess target organ toxicity in route-to-route extrapolation--the case of coumarin.

Coumarin (1,2-benzopyrone) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in humans by simulating both routes of exposure. The concentration-time profile in liver revealed a higher peak concentration (C(max-hep)) for the oral when compared to the dermal route. The area under the concentration-time curve in the liver (AUC(hep)) was found the same for both routes if the same extent of absorption is assumed. Dose response information from published rat studies were used to identify the metric relevant for liver toxicity. Liver exposure levels resulting from doses and durations as outlined in the studies were simulated in a rat model. We obtained 31 data pairs of C(max-hep) and AUC(hep). Liver toxicity was observed at doses which resulted in simulated C(max-hep) values exceeding a certain liver concentration whereas we could not identify a clear cut off value of AUC(hep). Our findings support the notion that liver toxicity of coumarin in rats is related to C(max-hep) rather than to AUC(hep). If these findings can be transferred to the situation in humans, the result demonstrates that route specific differences in organ peak concentrations have to be considered when performing route-to-route extrapolation.

Residue analysis of 500 high priority pesticides: better by GC-MS or LC-MS/MS?

This overview evaluates the capabilities of mass spectrometry (MS) in combination with gas chromatography (GC) and liquid chromatography (LC) for the determination of a multitude of pesticides. The selection of pesticides for this assessment is based on the status of production, the existence of regulations on maximum residue levels in food, and the frequency of residue detection. GC-MS with electron impact (EI) ionization and the combination of LC with tandem mass spectrometers (LC-MS/MS) using electrospray ionization (ESI) are identified as techniques most often applied in multi-residue methods for pesticides at present. Therefore, applicability and sensitivity obtained with GC-EI-MS and LC-ESI-MS/MS is individually compared for each of the selected pesticides. Only for one substance class only, the organochlorine pesticides, GC-MS achieves better performance. For all other classes of pesticides, the assessment shows a wider scope and better sensitivity if detection is based on LC-MS.

Heterologous expression of mouse cytochrome P450 2e1 in V79 cells: construction and characterisation of the cell line and comparison with V79 cell lines stably expressing rat P450 2E1 and human P450 2E1.

A V79 Chinese hamster cell line was constructed for stable expression of mouse cytochrome P450 2e1 (Cyp2e1), as an addition to the existing cell battery consisting of cell lines stably expressing rat CYP2E1 and human CYP2E1 (V79 Cell Battery). The aim was to establish a cell battery that offers the in vitro possibility of investigating species-specific differences in the toxicity and metabolism of chemicals representing substrates for CYP2E1. The newly established cell line (V79m2E1) effectively expressed Cyp2e1 in the catalytically active form. The expression of catalytically active CYP2E1 in V79m2E1 cells was maintained over several months in culture, as demonstrated by Western Blotting and chlorzoxazone (CLX) 6-hydroxylase activity. The cells exhibited CLX 6-hydroxylase activity with a Km of 27.8 microM/l and Vmax of 40 pmol/mg protein/minute, compared with a Km of 28.2/28.6 microM/l and a Vmax of 130/60 pmol/mg protein/minute from V79r2E1/V79h2E1 cells. Furthermore, the CYP2E1-dependent mutagenicity of N-nitrosodimethylamine could be demonstrated in the V79m2E1 cells. Therefore, the new cell battery permits the interspecies comparison of CYP2E1-dependent toxicity and of metabolism of chemicals between humans and the two major rodent species--the rat and the mouse--that are usually used in classical toxicity studies.