Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats

Wim H. De Jong, Eveline De Rijk, Alessandro Bonetto, Wendel Wohlleben, Vicki Stone, Andrea Brunelli, Elena Badetti, Antonio Marcomini, Ilse Gosens, Flemming R. Cassee

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)
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Copper oxide (CuO) nanoparticles (NPs) and copper carbonate nanoparticles (Cu2CO3(OH)2 NPs have applications as antimicrobial agents and wood preservatives: an application that may lead to oral ingestion via hand to mouth transfer. Rats were exposed by oral gavage to CuO NPs and Cu2CO3(OH)2 NPs for five consecutive days with doses from 1 to 512 mg/kg and 4 to 128 mg/kg per day, respectively, and toxicity was evaluated at days 6 and 26. Both CuO NPs and Cu2CO3(OH)2 NPs induced changes in hematology parameters, as well as clinical chemistry markers (e.g. increased alanine aminotransferase, ALT) indicative of liver damage For CuO NPs histopathological alterations were observed in bone marrow, stomach and liver mainly consisting of an inflammatory response, ulceration, and degeneration. Cu2CO3(OH)2 NPs induced morphological alterations in the stomach, liver, intestines, spleen, thymus, kidneys, and bone marrow. In spleen and thymus lymphoid, depletion was noted that warrants further immunotoxicological evaluation. The NPs showed partial dissolution in artificial simulated stomach fluids, while in intestinal conditions, the primary particles simultaneously shrank and agglomerated into large structures. This means that both copper ions and the particulate nanoforms should be considered as potential causal agents for the observed toxicity. For risk assessment, the lowest bench mark dose (BMD) was similar for both NPs for the serum liver enzyme AST (an indication of liver toxicity), being 26.2 mg/kg for CuO NPs and 30.8 mg/kg for Cu2CO3(OH)2 NPs. This was surprising since the histopathology evidence demonstrates more severe organ damage for Cu2CO3(OH)2 NPs than for CuO NPs.

Original languageEnglish
Pages (from-to)50-72
Number of pages23
Issue number1
Early online date19 Nov 2018
Publication statusPublished - 1 Feb 2019


  • Benchmark dose modeling
  • copper carbonate nanoparticles
  • copper oxide nanoparticles
  • dissolution and transformation
  • oral toxicity

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology


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