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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Neurotoxicity

Currently viewing:

Administrative data

Endpoint:
neurotoxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Nickel-induced neurodegeneration in the hippocampus, striatum and cortex; an ultrastructural insight, and the role of caspase-3 and α-synuclein
Author:
Ijomone OM, Olatunji SY, Owolabi JO, Naicker T, Aschner M
Year:
2018
Bibliographic source:
Journal of Trace Elements in Medicine and Biology 50:16-23

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: This study investigated nickel-induced neurodegeneration in rats treated with Nickel Chloride by examining ultrastructural changes in certain brain regions and investigating the role of caspase-3 and α-synuclein.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel chloride
EC Number:
253-399-0
EC Name:
Nickel chloride
Cas Number:
37211-05-5
Molecular formula:
NiCl2
IUPAC Name:
nickel(2+) dichloride
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material:
Sigma, St Louis, MO, USA

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Central Animal Holding, Babcock University
- Age at study initiation: Adults
- Weight at study initiation: 180 ± 20 grams
- Housing: Not stated
- Diet: Ad libitum
- Water: Ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
Not specified.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
Not stated but assumed daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
10 mg/kg bw/day (nominal)
Dose / conc.:
20 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Not specified.
Control animals:
yes, concurrent vehicle
Details on study design:
Not specified.

Examinations

Observations and clinical examinations performed and frequency:
None performed.
Neurobehavioural examinations performed and frequency:
None performed.
Other examinations:
Brain tissue prepared for electron microscopy with semi-quamtification of ultrastructural alterations in neurons in the hippocampus, striatum and cortex. Additional sections of various areas of brain tissue underwent immunohistochemical preparation and staining followed by digital image analysis for caspase-3 immunoreactivity and also for expression of the protein alpha-synuclein.
Statistics:
Digital image analysis results were analysed using one-way ANOVA followed by Turkey's multiple comparison tests with GraphPad Prism Version 7 statistical software.

Results and discussion

Results of examinations

Clinical signs:
not specified
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
effects observed, treatment-related
Description (incidence and severity):
Caspase-3 levels -
Caspase-3 immunoreactivity was increased in the CA3 (P = 0.0008) and DG (P = 0.0011) regions of the hippocampus and the striatum (P = 0.0002) of rats treated with 20 mg/kg.

α-synucelin expression -
Expression of α-synuclein was significantly increased in the cortex of rats treated with 20 mg/kg (P = 0.0009). No effects were observed in the hippocampus or striatum.
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
effects observed, treatment-related
Description (incidence and severity):
Hippocampus -
An increased incidence of "electron-dense" neurons were observed in rats treated with 20 mg/kg. "Electron-dense" nuclei exhibit a larger proportion of heterochromatin to euchachromatin, and can also be referred to as "dark neurons". These neurons also exhibited nuclei crenations, with increased cytoplasmic density. An increased incidence of mitochondrial abnormalities was also observed in the hippocampus of rats treated with 20 mg/kg.

Striatum -
An increased incidence of nuclei shrinking was observed in neurons of the striatum in rats treated with 10 and 20 mg/kg. An increased incidence of mitochondrial damage was also observed in the striatum of rats treated with 20 mg/kg.


Cortex -
An increased incidence of mitochondrial damage was observed in the cortex of rats treated with 10 and 20 mg/kg.
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
LOAEL
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
histopathology: non-neoplastic
other: gene expression / protein activity

Target system / organ toxicity

Critical effects observed:
yes
Lowest effective dose / conc.:
10 mg/kg bw/day (nominal)
System:
nervous system
Organ:
brain
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
yes

Applicant's summary and conclusion

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.