Toxic substances in consumer products, cosmetics and tobacco

Toxicological tests are mainly done today on individual substances. However as a rule consumers do not come into contact with individual substances but with complex substance mixtures: during the consumption of food as a consequence of migration of components in the food packaging to food and the use of body care products and other products like toys or clothing. Furthermore, reaction products may be formed during the production process and use of consumer products whose structure and toxicity are largely unknown. In this context some thought must also be given to substance interaction. There is, therefore, a need to examine the health safety of substance mixtures which may migrate from consumer products (like food packaging) to foods or migrate directly to man.

Examinations of the migration of substances from consumer products to food

The goal of studies on substance mixtures from consumer products is to identify problematic substances that are capable of migration like plasticizers, vulcanisation accelerators (mercaptobenzthiazole, thiurames) or azo dyes. For instance, azo dyes are used in toys, clothing and cosmetics as colouring agents and as hair dyes. Some azo dyes are known to be carcinogenic and allergenic; however, the available toxicological data are incomplete.

In order to establish criteria for the risk assessment of corresponding consumer products or to identify management options for products with harmful ingredients, the toxicological properties of migrating substances and their metabolites are to be recorded and their skin penetration potential determined.

Research areas

• Migration of plasticizers to food
  The sealing masses used in the twist off lids of glass containers for foods contain high levels of plasticizers, namely phthalates, major amounts of which may migrate to fat-containing food. Edible oils may also be contaminated with these substances due to the migration of plasticizers from the materials used during production and processing (e.g. tubes or containers). Very limited data are available to estimate the exposure to plasticizers from these sources.

• Perfluorinated chemicals in food packaging
  One of the possible causes which should be examined for the concentrations of perfluorooctanoic acid (PFOAs) in human blood is the possible migration of this substance and of fluorotelomer alcohols (FTOHs) from perfluorinated chemicals. These substances are used to give a grease-resistant and water-resistant finish to paper for food contact. There are indications that perfluoroalkanoic acids may be formed from FTOH in the human organism. PFOA has a very long half-life in the human body. Only very limited data on the migration of PFOA and FTOH have been available up to now for the estimation of this exposure pathway.

Toxicological studies with in vitro models

There is a need for research on product safety in both the analytical and toxicological areas. Various health-relevant effects of substance mixtures can now be examined in suitable cell cultures. One advantage of cell culture tests is the possibility of testing a large number of substance mixtures on the basis of different toxicological parameters. Analytically characterised migrates and defined migrate components are to be examined for their damaging, skin-irritating and sensitising effects on cells but also with regard to their possible mutagenic effect in cell cultures. Furthermore, in some selected migrates skin penetration is also determined in an in vitro model.

Research areas

• Toxicological studies on substances from consumer products
  The genotoxicity of azo dyes and their metabolites as well as vulcanisation accelerators is to be determined in a bacterial mutagenicity test (Ames Test) and in an in vitro test in mammalian cells (V79 micronucleus test). Furthermore, tests are to be conducted with eluates from dyed textiles and migrates from rubber materials.
  
  The genotoxicity of the model dye Direct Blue 14 and of its metabolite o-tolidine was examined in a bacterial mutagenicity test (Ames Test) and in an in vitro test in mammalian cells (V79 micronucleus test). Furthermore, initial tests were conducted with eluates from dyed textiles.

• Metabolism of azo dyes
  In vitro experiments with skin bacteria are to clarify the extent to which microbial metabolites of azo dyes contribute to the systemic availability of aromatic amines.
  
  Results:
  
  Azo cleavage into carcinogenic amines was demonstrated for three cosmetic dyes. The safety of these substances must, therefore, be questioned.
  
  A method for the quantification of azo cleavage was established and validated for one allergenic textile dye (Disperse Yellow 3). Proof was also provided for azo cleavage.

Other studies, in co-operation with the Charité University Clinic, Berlin, are to examine the sensitising potential of the azo dye and its metabolites. Parallel studies look at skin penetration.

• Development of a screening system for the toxicity of migrants from consumer products in keratinocytes
  
  Besides data on the toxicity of the substances, information on skin penetration in particular is required for risk assessments of the components of cosmetics and consumer products that come into contact with the body in order to determine systemic exposure. To this end, a method is to be established for the determination of skin penetration in human skin cells in vitro based on the OECD Guideline 428. Pesticides, azo dyes in textiles and vulcanisation accelerators from rubber materials are used as model substances.
  
  Results:
  
  For cell culture systems consisting of primary cells and cell lines a special method has been developed which permits the simultaneous detection of cell growth and programmed cell death (TUNEL- Ki67 double labelling). Hence, it supplements established methods of cytotoxicity measurement (MTT, neutral red test). Binary mixtures of model substances showed additive up to over-additive effects in cytotoxicity and apoptosis coupled with a parallel reduction in proliferation.

• Studies on contaminants in water pipe smoke
  
  Around 100 million people smoke water pipes around the world every day. This type of tobacco consumption is also on the increase in Germany. Initial studies show that the smoke of a water pipe contains high levels of carbon monoxide, metals and metal oxides. Traces of polycyclic hydrocarbons have also been identified. An initial study within BfR aims to provide information on exposure of water pipe smokers to this substance group.