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Toxicological information

Specific investigations: other studies

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Administrative data

chemobiokinetics general studies
Type of information:
experimental study
study currently ongoing
Adequacy of study:
weight of evidence
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference Type:
study report

Materials and methods

Test guideline
equivalent or similar to
other: ISO TS 18827:2017 Nanotechnologies
Version / remarks:
Electron spin resonance (ESR) as a method for measuring reactive oxygen species (ROS) generated by metal oxide nanomaterials
Principles of method if other than guideline:
Ferric Reduction Ability of Serum (FRAS) assay measures the surface reactivity of nanomaterials (NMs) under physiological conditions. The test material NMs are incubated with human blood serum (HBS). The antioxidative components in the serum serve as reporter molecules as they are comsumed during incubation with the NMs. After, the NMs are centrifuged and the supernatant human blood serum is incubated in the FRAS reaction with Fe3+. The reduction of Fe3+ to Fe2+ is detected optically by a color change from transparent to blue. A high consumption of antioxidative components will be observed in a reduction of the blue color.
GLP compliance:
Type of method:
other: in chemico
Endpoint addressed:
basic toxicokinetics
other: surface reactivity

Test material

Test material form:

Administration / exposure

Route of administration:
other: test material is in direct contact to humane serum
Duration of treatment / exposure:
180 min
Frequency of treatment:
one treatment
No. of animals per sex per dose:
- replicates: triplicate
Details on study design:
- 10 mg of test item applied to 100% human serum (Sigma Aldrich, P2918-100mL) at 37°C for 180 min
- the sample and serum are centrifuged at 14,000 g (11,900 rpm in specific centrifuge) for 150 minutes
- the FRAS substances are handled in the dark
- calibration of the FRAS absorption signal with a concentration series of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water-soluble analogue of vitamin E
- Blank: pure serum


- measurement of UV/VIS absorption at 500-700 nm
- Metric:Surface-based biological oxidative damage (sBOD) in nM Trolox-equivalent units (TEU) per m² of nanomaterial surface = nM TEU / m² , at a nanomaterial concentration of 1 m² /mL.
Positive control:
Mn2O3 (insoluble), CuO (partially soluble)

Results and discussion

Applicant's summary and conclusion