Food for thought...on alternative methods for chemical safety testing.

About 70 million chemicals have been synthesized, as registered in Chemical Abstracts Service. It is not really clear how many are found in consumer products and the environment. Why not? First, because registrations are only required for certain production volumes. Second, no organization or entity tracks increases in production volumes. I am not aware, for example, of very many new chemicals (in Europe, those notified after September 1981) that have been reregistered and subjected to additional testing demands due to higher production volume; this might be a reason why practically all new chemicals (registered from 1981-2006) have been pre-registered again for ReACH, from which they are exempted in principle. Similarly, no procedures exist to track when thresholds for registration are exceeded on a european level by different manufacturers combined, when originally only tiny amounts were produced. In europe, until 2007, the threshold for notification was 100 kg (now 1 ton) per year, which resulted in about 300 files per year. In the smaller US chemical industry the number of premarketing notifications is about 2,000 per year, giving us an idea about how few chemicals are accurately monitored in europe. third, requirements for registration differ considerably. Many chemicals enter our markets as components of products. Who registers when a sport shoe manufactured somewhere in Asia is imported and its fashionable, decorative glitter is produced by chemicals? Sure customs (and prior to ReACH directive 67/548/eeC) ask for documentation but in practice many importers are not aware of every component of the product. Fourth, many additional compounds, especially in the environment, are decomposition and reaction products. Fifth, things get really difficult when we also have to think of different formulations as particles. It is well known that nanoparticles (i.e. chemical particles typically between 1 and 100 nm) change their behavior depending on size and shape. A whole new field of nanotoxicology is emerging, which will be the subject of a future article in this series. But effects relevant to toxicity also occur on a larger scale. We know that both crystal sizes and shapes of drugs affect bioavailability and side-effects. A reasonable estimate is that people are exposed to about 100,000 relevant synthetic chemicals (84,000 are listed in the cumulative US tSCA inventory, 100,000 in the eU eINeCS inventory) in contrast to the 5,000 to 10,000 for which actually (widely varying in depth) safety assessments exist. the knowledge gap is, from this view, tremendous. this gap is even deeper if we consider the effect of chemicals in mixtures, where synergies may occur as recently addressed by the eU Council of environment Ministers (http:// register.consilium.europa.eu/pdf/en/09/st17/st17820.en09.pdf). However, we are most likely exposed to an even larger number of chemicals, given all the naturally occurring sources. I was once very much impressed when I learned that a plant extract used as a drug can contain 40,000 substances. With regard to possible toxic properties, there is no difference between a substance produced by chemical synthesis or by the metabolism of an organism – on the contrary, some of the most toxic substances are “natural” because evolution has optimized these poisons. Similarly, there are byproducts from chemical synthesis to be considered. Petrochemicals fall somewhere in-between, as they are very heterogeneous as natural products to start with and fractionation will always remain partial.