Research on the carcinogenicity of nanoparticles and other dusts
The primary aims of the study were to analyse differences between the carcinogenicity of granular dusts in the rat lung after intratracheal instillation, to find out the optimal dose metric for their carcinogenic potency and to interprete their potential relevance for human health. Nineteen dusts were choosen for the experiment, which differed at least in one of the following properties of their particles: chemical composition, density, specific surface area (according to the so called BET method) and mean particle size. Quartz and amorphous silica were included in the study as dusts with known specific toxicity; little was known about the toxicity of some dusts. Also, coated hydrophobic TiO2 had been selected that had not been tested before and showed strong acute toxicity.
Sixteen of the 19 dusts formed a group for which no specific toxicity was detected which seemed to be essential for their carcinogenicity in this experiment. Accordingly, these dusts were defined as respirable granular bio-durable particles without known significant specific toxicity (GBP, the three letters of the abbreviation are to cover all nine words) in the frame of this carcinogenicity experiment. Regarding the size of the primary particles, 4 of the 16 GBP were clearly ultrafine dusts (GBP-UF, mean diameters 0.01 - 0.03 µm); they are also called nanoparticles. The other 12 GBP were classified as fine dusts (GBP-F, mean diameters 0.09 - 4.0 µm). The results suggested subdividing this large group into two groups with different diameters: 4 small-fine dusts (GBP-F-sm, mean diameters 0.09 - 0.2 µm) and 8 large-fine dusts (GBP-F-la, mean diameters 1.8 - 4 µm).
All 16 GBP produced lung tumours, many more than expected. The microscopically diagnosed lung tumour incidences were used for non-linear regression analysis. The GBP volume in connection with particle size turned out to be the most adequate dose metric for the carcinogenicity of GBP. The 4 tested GBP-UF were about 2 times more effective than the "small" GBP-F-sm and 5- to 6 times more effective than the "large" GBP-F-la.
An effect threshold of carcinogenicity of GBP in the range of the General Threshold Limit Value for Dust is extremely unlikely for rats, if all inhalation and instillation studies are considered. The additional cancer risk after exposure of rats to GBP-F was calculated as 1 - 3 % for the exposure scenario of the General Threshold Limit Value for respirable dust of 3 mg/m³, which is in force since 2001. Many arguments speak against the hypothesis that the mechanism which causes the dust related lung tumours in rats does not exist in humans. Some epidemiological data indicate that a similar carcinogenic potency may exist for humans and rats related to the long-term (i.e. same proportion of life expectancy) exposure concentration. However, the limit for a statistically "unequivocally" increased risk is very high (absolute excess risk greater than 5 - 10 %) for the most studies both with humans and with rats. Overall, the state of knowledge meets the EU criteria for a classification of GBP into category 2 of carcinogenic substances.
The results of this project are currently beeing discussed in a working group with members of the subcommittee "Hazard risk assessment" (III) of the German Committee on Hazardous Substances (AGS) and members of the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission).
Please download the complete report "Research on the carcinogenicity of nanoparticles and other dusts" (in German only).
Research on the carcinogenicity of nanoparticles and other dusts.
1. edition. Dortmund: Bundesanstalt für Arbeitsschutz und Arbeitsmedizin 2008.
ISBN: 978-3-88261-069-7, pp. 309, Project number: F 2083, paper, pdf file
Signatures of the BAuA library:
B424/LH100/21, DM19/LH100/21, D122/LH100/21