Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific methods, non-standard test.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Effect of nickel sulfate on male rats.
Author:
Mathur, A.K., K.K. Datta, S.K. Tandon, and T.S.S. Dikshith.
Year:
1977
Bibliographic source:
Bulletin of Environmental Contamination and Toxicology. 17(2):241-248.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A particular Test Guideline was not specified in this study.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nickel Sulfate Hexahydrate, 10101-97-0
- Molecular formula (if other than submission substance): not different than submission substance
- Molecular weight (if other than submission substance): not different than submission substance
- Smiles notation (if other than submission substance): not different than submission substance
- InChl (if other than submission substance): not different than submission substance
- Structural formula attached as image file (if other than submission substance): not different than submission substance
- Other details not reported or not applicable

Test animals

Species:
rat
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Male rats
- Weight at study initiation: (160 +/- 10 g) 
- Other details not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 +/-2 deg C
- Humidity (%): 60-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

IN-LIFE DATES: not reported

Administration / exposure

Type of coverage:
open
Vehicle:
other: normal saline
Details on dermal exposure:
TEST SITE
- Area of exposure: The hair on each animal's lateroabdominal area (approximately 4x4 cm) was clipped off and cleaned with an ethanol-acetone 
(1:1) mixture. 
- % coverage: not reported
- Type of wrap if used: not used, painted on

REMOVAL OF TEST SUBSTANCE
- not reported

TEST MATERIAL
-  Rats from group I, II and III were  painted daily for 30 days with 40, 60 and 100 mg Ni/kg, respectively in the form of NiSO*6H20 dissolved in 0.25 ml of normal saline.  An equal  volume of saline was applied on the skin of group IV animals, which served as a control. 

VEHICLE
- no data
Duration of exposure:
30 days
Doses:
40, 60 and 100 mg Ni/kg,
No. of animals per sex per dose:
8
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 15 or 30 days
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: yes, Skin, liver, kidney, and testes were removed and fixed for histopathological examination.
- Other examinations performed: none
Statistics:
None

Results and discussion

Preliminary study:
none reported
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 100 mg/kg bw
Remarks on result:
other: Dose is in mg Ni/kg BW
Mortality:
No mortality occurred
Clinical signs:
No clinical signs during exposure
Body weight:
Not measured
Gross pathology:
Macroscopic observations: No gross changes were noticed in the skin, liver, kidney, or testes of rats painted with nickel sulphate.  There was  
no liver enlargement and the weight of liver showed no significant difference from those of controls.  The testes did not show any marked  
atrophy or hypertrophy.  The colour and weight of testes from test animals did not differ significantly from those of controls.
Microscopic observations: After 15 days of exposure to nickel sulphate, no significant changes in the testes were observed, while mild effects  
were seen in the skin (at 100 mg Ni/kg) and liver (at 60 mg Ni/kg).   Liver and testes were normal after 30 days exposure in the 40 mg Ni/kg  
group, but changes were noted at higher exposures.  Skin showed slight hyperkeratinization at 40 mg Ni/kg with more significant changes at 60  
and 100 mg Ni/kg.  No abnormality was observed in kidney of the nickel sulphate-treated rats at any exposure tested.
Other findings:
none reported

Any other information on results incl. tables

Effect level was not reported.

Applicant's summary and conclusion

Conclusions:
NiSO4.6H2O corresponding to 40, 60, 100 mg Ni/kg in 0.25% normal saline daily for 30 days was administered to the skin of male rats and no clinical signs of poisoning or mortality were found.
Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.

 

Robust Summary of Mathur et al. 1977: Thirty two male albino rats (160 +/- 10 g) were divided into four groups of 8 animals each. The hair on each animal's lateroabdominal area (approximately 4x4 cm) was clipped off and cleaned with an ethanol-acetone (1:1) mixture. Rats from group I, II and III were painted daily for 30 days with 40, 60 and 100 mg Ni/kg, respectively in the form of NiSO*6H20 dissolved in 0.25 ml of normal saline. An equal volume of saline was applied on the skin of group IV animals, which served as a control. Four animals from each group were sacrificed after 15 and 30 days of application. Skin, liver, kidney, and testes were removed and fixed for histopathological examination.

 

Morbidity and Mortality: There were no clinical symptoms of poisoning or mortality among experimental animals due to the dermal application of nickel sulphate at doses up to 100 mg Ni/kg.

 

Macroscopic observations: No gross changes were noticed in the skin, liver, kidney, or testes of rats painted with nickel sulphate. There was no liver enlargement and the weight of liver showed no significant difference from those of controls. The testes did not show any marked atrophy or hypertrophy. The colour and weight of testes from test animals did not differ significantly from those of controls. 

 

Microscopic observations: After 15 days of exposure to nickel sulphate, no significant changes in the testes were observed, while mild effects were seen in the skin (at 100 mg Ni/kg) and liver (at 60 mg Ni/kg). Liver and testes were normal after 30 days exposure in the 40 mg Ni/kg group, but changes were noted at higher exposures. Skin showed slight hyperkeratinization at 40 mg Ni/kg with more significant changes at 60 and 100 mg Ni/kg. No abnormality was observed in kidney of the nickel sulphate-treated rats at any exposure tested. Due to a lack of mortality, the LD0 for nickel sulphate was reported as >100 mg Ni/kg.