title: Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials.
abstract: Materials that can be described as respirable granular biodurable particles without known significant specific toxicity (GBP) show a common mode of toxicological action that is characterized by inflammation and carcinogenicity in chronic inhalation studies in the rat. This study was carried out to compare the carcinogenic potency of GBP nanomaterials (primary particle diameter 1-100 nm) to GBP micromaterials (primary particle diameter >100 nm) in a pooled approach. For this purpose, the positive GBP rat inhalation carcinogenicity studies have been evaluated. Inhalation studies on diesel engine emissions have also been included due to the fact that the mode of carcinogenic action is assumed to be the same. As it is currently not clear which dose metrics may best explain carcinogenic potency, different metrics have been considered. Cumulative exposure concentrations related to mass, surface area, and primary particle volume have been included as well as cumulative lung burden metrics related to mass, surface area, and primary particle volume. In total, 36 comparisons have been conducted. Including all dose metrics, GBP nanomaterials were 1.33- to 1.69-fold (mean values) and 1.88- to 3.54-fold (median values) more potent with respect to carcinogenicity than GBP micromaterials, respectively. Nine of these 36 comparisons showed statistical significance (p < 0.05, U test), all of which related to dose metrics based on particle mass. The maximum comparative potency factor obtained for one of these 9 dose metric comparisons based on particle mass was 4.71. The studies with diesel engine emissions did not have a major impact on the potency comparison. The average duration of the carcinogenicity studies with GBP nanomaterials was 4 months longer (median values 30 vs. 26 months) than the studies with GBP micromaterials, respectively. Tumor rates increase with age and lung tumors in the rat induced by GBP materials are known to appear late, that is, mainly after study durations longer than 24 months. Taking the different study durations into account, the real potency differences were estimated to be twofold lower than the relative potency factors identified. In conclusion, the chronic rat inhalation studies with GBP materials indicate that the difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials is low can be described by a factor of 2-2.5 referring to the dose metrics mass concentration.
authors.affiliation: Federal Institute for Occupational Safety and Health, Dortmund, Germany. gebel.thomas@baua.bund.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebel
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008422:Materials Testing; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D013045:Species Specificity; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D052638:Particulate Matter; D001335:Vehicle Emissions