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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions. The report lacked information on environmental conditions and dose volume administered.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Similar to OECD 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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
- Substance type: Pure product
- Physical state: liquid
- Analytical purity: 98.8%
- Impurities (identity and concentrations): Cu <0.001%, Fe 0.001%, Zn 0.003%
- Other details not reported or not applicable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA, USA.  
- Age at study initiation: young adult
- Weight at study initiation:  Fasted body weights ranged from 249.8-285.8 g for males and 216.8-222.4 g for females.  
- Fasting period before study: yes, the night prior
- Housing: individually housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days prior to testing.  

ENVIRONMENTAL CONDITIONS: controlled, no details

IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
Two studies were conducted, an initial dose range-finding study and a subsequent main study.  
The dose levels chosen for the main study, based on the results of the range-finding study, were 100, 178, 316, 562, and 1000 mg/kg.

VEHICLE: water
- Concentration in vehicle: not reported
- Amount of vehicle (if gavage): 20 ml

MAXIMUM DOSE VOLUME APPLIED: 10 g test article in 20 ml diluent

Doses:
100, 178, 316, 562, and 1000 mg/kg
No. of animals per sex per dose:
10 (5 males and 5 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed frequently for signs of toxicity or mortality and body weights were measured on days 0 (i.e., test initiation), 8, and 15, or at death. 
- Necropsy of survivors performed: yes, surviving animals were sacrificed on day 15, and all animals were necropsied and examined for abnormalities. 
- Other examinations performed: clinical signs and body weight
Statistics:
Acute oral toxicity values (w/ 95% confidence limits) were calculated from the mortality data using the method of Miller and Tainter (1944).   
Dose-mortality curves were plotted (normal log graph).

Results and discussion

Preliminary study:
A range finding study was performed, dose/mortality after 8 days:
100 mg/kg = 0/4
266 mg/kg = 1/4
707 mg/kg = 4/4
1880 mg/kg = 4/4
5000 mg/kg = 4/4

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
300 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
325 mg/kg bw
95% CL:
121 - 529
Sex:
female
Dose descriptor:
LD50
Effect level:
275 mg/kg bw
95% CL:
140 - 410
Mortality:
Cumulative mortality observed (number of mortalities observed/total number of animals tested), by nominal dose administered:
100 mg/kg: 0/5 males; 0/5 females
178 mg/kg: 0/5 males; 1/5 females (death occurred on day 1)
316 mg/kg: 2/5 males; 3/5 females (deaths occurred on day 1)
562 mg/kg: 5/5 males; 5/5 females (deaths occurred by day 5)
1000 mg/kg: 5/5 males; 5/5 females (deaths occurred by day 2)
Clinical signs:
Symptoms observed in more than one animal/dose group were decreased activity (all dose groups) and ataxia (316, 562, and 1000 mg/kg groups).  
Body weight:
Mean body weights of surviving rats increased during the 15-day study period. 
Gross pathology:
Necropsy findings were negative, except for the 562 and 1000 mg/kg dose groups where bloodlike viscous liquid was found in the  
intestines of 1-2 animals/dose group. 
Other findings:
none reported

Any other information on results incl. tables

A NOAEL of 22 mg Ni/kg/day (100 mg NiSO4.6H2O/kg/day) was observed.

Applicant's summary and conclusion

Conclusions:
Oral LD50 was 72 mg Ni/kg (325 mg NiSO4.6H2O /kg) (males) and 61 mg Ni/kg (275mg NiSO4.6H2O/kg) (females). A NOAEL of 22 mg Ni/kg/day (100 mg NiSO4.6H2O/kg/day) was observed.
Executive summary:

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.

The acute toxicity of the test substance was determined by oral administration to male and female Sprague Dawley rats.  Test animals were  

obtained from Charles River Breeding Laboratories, Inc., Wilmington, MA, USA.  Animals were individually housed, provided food and water ad  

libitum, and acclimatized for at least 5 days prior to testing.  The test substance was dissolved in water.

Two studies were conducted, an initial dose range-finding study and a subsequent main study.  Animals were fasted overnight prior to initiation  

of the main study.  The dose levels chosen for the main study, based on the results of the range-finding study, were 100, 178, 316, 562, and 1000 mg/kg. 

Groups of 10 animals (5 males and 5 females) received a single  oral dose of one of the test substance concentrations.


Animals were observed frequently for signs of toxicity or mortality and body weights were measured on days 0 (i.e., test initiation), 8, and 15,  

or at death.  Fasted body weights ranged from 249.8-285.8 g for males and 216.8-222.4 g for females.  Surviving animals were sacrificed on day 15,  

and all animals were necropsied and examined for abnormalities.  Acute oral toxicity values (w/ 95% confidence limits) were calculated from the  

mortality data using the method of Miller and Tainter (1944).  Dose-mortality curves were plotted (normal log graph).

Cumulative mortality observed (number of mortalities observed/total number of animals tested), by nominal dose administered:
100 mg/kg: 0/5 males; 0/5 females
178 mg/kg: 0/5 males; 1/5 females (death occurred on day 1)
316 mg/kg: 2/5 males; 3/5 females (deaths occurred on day 1)
562 mg/kg: 5/5 males; 5/5 females (deaths occurred by day 5)
1000 mg/kg: 5/5 males; 5/5 females (deaths occurred by day 2)

Symptoms observed in more than one animal/dose group were decreased activity (all dose groups) and ataxia (316, 562, and 1000 mg/kg groups).  

Mean body weights of surviving rats increased during the 15-day study period.  Necropsy findings were negative, except for the 562 and 1000  

mg/kg dose groups where bloodlike viscous liquid was found in the intestines of 1-2 animals/dose group. 

Acute oral toxicity (LD50) values (95% confidence limits), by sex tested:
LD50 (males): 325 (121-529) mg/kg bw
LD50 (females): 275 (140-410) mg/kg bw
LD50 (both sexes): 200 (101-299) mg/kg bw

STUDY RATED BY AN INDEPENDENT REVIEWER.