Nickel bis(dihydrogen phosphate)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

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

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other 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

Test material information

Constituent 1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

NiSO4

IUPAC Name:

nickel(2+) sulfate

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 or test system 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:

other: No clinical signs during exposure

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.