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The substance 3-(4-methylbenzylidene)camphor (4-MBC, CAS-No. 36861-47-9 as well as 38102-62-4) is used as UV-filter in cosmetics, mainly in sunscreen lotions. National as well as European evaluations are available for the substance, especially from the Scientific Committee on Consumer Products (SCCP). The SCCP did not derive a TDI-value, but used for a MoS assessment a NOAEL of 25 mg/(kg bw · d) based on effects on the thyroid gland of rats in a subchronic study with oral administration. Newer studies, however, indicate lower NOAEL values, leading to tolerable daily intakes of 0,01 mg/kg bw. The HBM Commission established for the metabolite 3-(4-carboxybenzylidene)camphor (3-4CBC) HBM-I values of 0,09 mg/l urine for adults and 0,06 mg/l urine for children. HBM-I values for the metabolite 3-(4-carboxybenzylidene)-6-hydroxycamphor (3-4CBHC) were set at 0,38 mg/l urine for adults and 0,25 mg/l urine for children. The rounded HBM-I value for the sum of metabolites 3-4CBC und 3-4CBHC is accordingly 0,5 mg/l urine for adults and 0,3 mg/l urine for children.

1-Methyl-pyrrolidone (NMP) is used as a solvent in many technical applications. The general population may be exposed to NMP from the use as ingredient in paint and graffiti remover, indoors also from use in paints and carpeting. Because of developmental toxic effects, the use of NMP in consumer products in the EU is regulated. The developmental effects accompanied by weak maternally toxic effects in animal experiments are considered as the critical effects by the German HBM Commission. Based on these effects, HBM-I values of 10 mg/l urine for children and of 15 mg/l for adults, respectively, were derived for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide. HBM-II-values were set to 30 mg/l urine for children and 50 mg/l for adults, respectively. Because of similar effects of the structural analogue 1-ethyl-2-pyrrolidone (NEP), the possible mixed exposure to both compounds has to be taken into account when evaluating the total burden.

2-Mercaptobenzothiazole (2-MBT, CAS No. 149-30-4) is mainly used as a vulcanization accelerator in the production of rubber. Other applications are as a fungicide in paints and varnishs and for the external treatment of animals. Because of its manifold application in consumer products, for example in soothers, exposure of the general population to 2-MBT can't be excluded. For the purpose of a toxicological evaluation of a possible body burden, the German HBM-commission derived HBM-I values for 2-MBT in the urine of children and adults. The no observed adverse effect level of 94 mg/kg bw/d from a subchronic oral study with mice was used as the point of departure. After considering a total assessment factor of 350, a tolerable daily intake of 0.3 mg/kg bw/d was deduced for humans. Considering further the percentage of 2-MBT and its glucuronide excreted in urine together with the body weight proportional urine volume leads to an HBM-I value for 2-MBT of 4.5 mg/l urine for children and 7 mg/l urine for adults.

N-Ethyl-2-pyrrolidone (NEP), a polar aprotic solvent, is used in many applications as substitute for the structural analogue N-methyl-2-pyrrolidone (NMP), e. g. for surface coatings, in cleaning agents and paint strippers. Monitoring studies indicate that individuals within the general public, without occupational exposure, may be exposed to NEP to an extent, which is comparable to NMP. As NMP, NEP presents a potential health hazard due to its developmental toxicity and teratogenicity. Exposure to NEP can be quantified by the determination of the excretion of its urinary metabolites 5-Hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-Hydroxy-N-ethylsuccinimide (2-HESI). For the derivation of HBM values, the german Human Biomonitoring Commission (HBM commission) evaluated different toxicological endpoints and finally decided on the BMDL05 and the BMD10 for the endpoint “reduced grasp intensity” of a subchronic feeding study with rats as point of departure (POD) for further procedural steps. The resulting HBM-I and HBM-II values for the sum of the metabolites 5-HNEP and 2-HESI in the urine of children are 10 resp. 25 mg/l and in the urine of adults are 15 resp. 40 mg/l. If the HBM values are exceeded, a check-up will be necessary at first. Measurements above the HBM-II value give cause for concern, especially for pregnant women. Air measurements to determine the source of exposure can be useful. The possibility of skin absorption from use of cleaning agents and paint strippers should also be traced. As NEP und NMP have similar toxic effects, a potential mixed exposure to both substances has to be taken into account.

In order to ensure the quality of biomedical products, an experimental test for every single manufactured batch is required for many products. Especially in vaccine testing, animal experiments are traditionally used for this purpose. For example, efficacy is often determined via challenge experiments in laboratory animals. Safety tests of vaccine batches are also mostly performed using laboratory animals. However, many animal experiments have clear inherent disadvantages (low accuracy, questionable transferability to humans, unclear significance). Furthermore, for ethical reasons and animal welfare aspects animal experiments are also seen very critical by the public. Therefore, there is a strong trend towards replacing animal experiments with methods in which no animals are used ("replacement"). If a replacement is not possible, the required animal experiments should be improved in order to minimize the number of animals necessary ("reduction") and to reduce pain and suffering caused by the experiment to a minimum ("refinement"). This "3R concept" is meanwhile firmly established in legislature. In recent years many mandatory animal experiments have been replaced by alternative in vitro methods or improved according to the 3R principles; numerous alternative methods are currently under development. Nevertheless, the process from the development of a new method to its legal implementation takes a long time. Therefore, supplementary regulatory measures to facilitate validation and acceptance of new alternative methods could contribute to a faster and more consequent implementation of the 3R concept in the testing of biomedical products.

International standards are prepared as materials assigned an arbitrary unitage for a biological activity by the Expert Committee on Biological Standardization of the World Health Organization. Working reference materials are calibrated against international standards giving a common unit of measurement between laboratories. The references are assessed by a collaborative study including all relevant assays rather than by a single reference method as in the SI (Le Système international d'unités) system and the unitage assigned is an arbitrary value derived from a consensus of all valid methods. The process has proved valuable in assaying the activity of therapeutic biological medicines and in standardizing certain types of diagnostics. Issues arise with maintaining the unit when the primary reference must be replaced and to some extent in assessing the commutability of the reference with real life analytes.

The Biological Standardisation Programme (BSP) of the European Directorate for the Quality of Medicines & HealthCare (EDQM) was founded in 1992 with the objective to provide the necessary tools for the quality controls prescribed by the European Pharmacopoeia (Ph. Eur.). The BSP accomplishes this task by establishing reference standards and materials, as well as standardised control methods. A key aspect of BSP's work on development of methods is the validation of methods which can replace Ph. Eur. tests involving animals. The current area of work includes vaccines (for human and animal use), medicines produced from human plasma, hormones, cytokines, allergens, as well as reference materials and methods for determination of impurities and contaminations. BSP closely collaborates with the World Health Organization (WHO) and national authorities; many reference standards are established in joint projects with WHO. Participants of studies for establishing of reference materials and methods are mainly national control laboratories and manufacturers. BSP has to date run 131 projects, whereby 121 reference materials were established. Method development was the objective of 38 projects, with 21 thereof aiming at replacement of animal tests. BSP is funded by the EDQM (Council of Europe) and by the European Commission. With its activities BSP makes a significant contribution to quality, safety and efficacy of biological medicinal products in Europe and beyond, and serves thereby health and well-being of human beings and animals.

Bisphenol A (BPA) is used for the production of polycarbonates and synthetic resins. Many of the items that contain BPA, for example polycarbonate bottles and coated cans, are commodities from which BPA can migrate into food and drinks, resulting in ubiquitous exposure of the population. Numerous animal studies and in vitro tests have shown that BPA acts as an "endocrine disruptor". Because of the still incomplete understanding of the complex and contradictory effects of BPA at doses below the NOAEL, the toxicological significance of recent findings is uncertain. The German HBM Commission takes notice that the risk assessment is currently in flux and that in the EU and other countries precautionary bans on BPA have been introduced. In the light of the extensive and growing body of literature, the Commission does not see itself in a position to resolve this controversy, nor to answer the question of the relevance of observed effects of low BPA doses on human health. The Commission has derived reference values (RV95) and TDI-based HBM I values for total BPA in urine. The RV95 values are 30 μg/l for 3-5 year olds, 15 μg/l for 6-14 year olds, and 7 μg/l for 20-29 year olds. The HBM I value for children is 1.5 mg/l and 2.5 mg/l for adults, respectively. The Commission emphasizes that the HBM values will require immediate adjustment should the current TDI of 0.05 mg/kg bw/day be changed. For the practical application of HBM, the Commission recommends an assessment based on the RV95. Confirmed exceedance of the RV95 by repeat measurements should prompt a search for the possible source(s), following the ALARA principle.