Table 2.
In vivo new genotoxicity studies on nickel
| Endpoint and experimental system | Test substance | Exposure conditions | Result | Comments | Reference |
|---|---|---|---|---|---|
| Chromosomal aberrations Male mice bone marrow N = 5/group | NiCl2 Vehicle: not specified Positive control: endoxan Negative control: vehicle | Single i.p. treatment at 0, 2.62, 5.25, 10.5 and 21.0 mg/kg bw Harvesting: 24 h Repeated i.p. treatment at 2.62, 5.25 and 10.5 mg/kg bw per day for 1, 2 or 3 weeks | Single treatment: dose‐dependent increase in % abnormal metaphases (fragment/breaks, deletions, translocations, endomitosis) from 5.25 mg/kg bw onwards Positive Repeated treatment: 1 week: increased % of abnormal metaphases at the two highest doses second and third weeks: increased abnormal metaphases at all doses Positive | Cumulative effect of repeated dosing of NiCl2 | Fahmy et al. (2014) |
| Chromosomal aberrations Male mice spermatocytes N = 5/group | NiCl2 Vehicle: not specified Positive control: endoxan Negative control: vehicle | Single i.p. treatment at 0, 2.62, 5.25, 10.5 and 21.0 mg/kg bw Harvesting: 24 h Repeated i.p. treatment at 2.62, 5.25 and 10.5 mg/kg bw per day for 1, 2 or 3 weeks | Single treatment: dose‐dependent increase in % abnormal metaphases (separation of X‐Y and autosomal univalent, fragment/breaks) from 5.25 mg/kg bw Positive Repeated treatment: Dose‐ and time‐dependent increase in % abnormal metaphases at all doses Positive | The authors report a significant dose‐dependent increase in the % of sperm abnormalities (heads and tails) | Fahmy et al. (2014) |
| Chromosomal aberrations (structural and numerical) adult male Swiss albino mice Bone marrow N = 12/group | NiCl2 Vehicle: saline Positive control: not included Negative control: vehicle | 2.3, 4.7 and 7.0 mg/kg bw (s.c. injection) 24‐h exposure 800 cells scored | Dose‐related increase in % aberrant cells (without gaps) (significant only at the highest dose) (induction of gaps, breaks, fragments and exchanges) Increase incidence of aneuploidy in all groups. Ratio hypoploidy (38/39 chromosomes)/hyperploidy (41/42 chromosomes): between 2.1 and 3:1 Increased incidence of polyploidy (3 N) Positive | Clastogenic and aneugenic effects were associated with oxidative stress (increased lipid peroxidation and NO, decreased GSH levels) and cytotoxicity (Lactate dehydrogenase) | El‐Habit and Abdel (2014) |
| Micronuclei Adult male Swiss albino mice Bone marrow N = 12/group | NiCl2 Vehicle: saline Positive control: not included Negative control: vehicle | 2.3, 4.7 and 7.0 μmol/kg bw (s.c. injection) Harvesting; 24 h | Significant increase in MNPCE (4–9‐folds) at all doses Dose‐related decrease in PCE/NCE Positive | 500 PCE scored | El‐Habit and Abdel (2014) |
| SSBs (comet assay) Adult male Swiss albino mice Bone marrow N = 12/group | NiCl2 Vehicle: saline Positive control: not included Negative control: vehicle | 2.3, 4.7 and 7.0 μmol/kg bw (s.c. injection) | Dose‐dependent increase in SSBs at all doses Positive | El‐Habit and Abdel (2014) |
NiCl2: nickel chloride; i.p.: intraperitoneal; N: number of animals; PCE: polychromatic erythrocytes; NCE: normochromatic erythrocytes; MNPCE: micronucleated polychromatic erythrocytes; s.c.: subcutaneous; SSBs: single‐strand breaks; GSH: glutathione.