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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:
not reported
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
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
According to OECD 401
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel dichloride
EC Number:
231-743-0
EC Name:
Nickel dichloride
Cas Number:
7718-54-9
Molecular formula:
Cl2Ni
IUPAC Name:
nickel(2+) dichloride
Constituent 2
Reference substance name:
98.8%
IUPAC Name:
98.8%
Constituent 3
Reference substance name:
NiPERA.
IUPAC Name:
NiPERA.
Details on test material:
- Name of test material (as cited in study report): Nickel chloride Hexahydrate
- 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): Fe 0.001%, Cu 0.001%, SO4 0.008%, H2O insoluble < 0.01%
- Composition of test material, percentage of components: not applicable
- Isomers composition: not applicable
- Purity test date: not reported
- Lot/batch No.: 072182
- Other details on test material not reported or not applicable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA, USA. 
- Age at study initiation: not reported, young
- Weight at study initiation: mean body weight on day 1 = 352.4 - 375.6 grams
- Fasting period before study: food witheld the night prior to dosing
- Housing: Animals were 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
- not reported

IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 grams test article, in 20 mls H20 (50% w/v)
- Amount of vehicle (if gavage): 20 mls H2O
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD: not applicable
Doses:
50, 98, 194, 381, and 750 mg/kg
No. of animals per sex per dose:
10 (5 males and 5 females)
Control animals:
no
Details on study design:
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 50, 98, 194, 381, and 750 mg/kg.  

- 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
- 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:
Mortality after 8 days:
100 mg/kg = 0/4
266 mg/kg = 3/4
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:
200 mg/kg bw
95% CL:
186 - 214
Sex:
male
Dose descriptor:
LD50
Effect level:
210 mg/kg bw
95% CL:
159 - 261
Sex:
female
Dose descriptor:
LD50
Effect level:
175 mg/kg bw
95% CL:
131 - 219
Mortality:
Cumulative mortality observed (number of mortalities observed/total number of animals tested), 
by nominal dose administered:
50 mg/kg: 0/5 males; 0/5 females
98 mg/kg: 0/5 males; 0/5 females
194 mg/kg: 3/5 males; 4/5 females (deaths occurred by day 2)
381 mg/kg: 4/5 males; 5/5 females (deaths occurred on day 1)
750 mg/kg: 5/5 males; 5/5 females (deaths occurred on day 1)
Clinical signs:
Symptoms observed in more than one animal/dose group were decreased activity (98, 194, and 381 mg/kg groups), 
salivation (98 and 194 mg/kg groups), and ataxia and swollen limbs (194 mg/kg group).
Body weight:
Mean body weights of surviving rats increased during the 15-day study period.   
Gross pathology:
Necropsy findings were negative for all dose groups.
Other findings:
none reported

Any other information on results incl. tables

NOAEL of 100 mg/kg bw (or ~20 mg Ni/kg bw/day)

Applicant's summary and conclusion

Conclusions:
The calculated oral LD50 for male rats was found to be 210 mg/kg body weight with a 95% confidence interval of 159 to 261 mg/kg. 
The calculated oral LD50 for female rats was found to be 175 mg/kg body weight with a 95% confidence interval of 131 to 219 mg/kg
The combined response was found to be 200 mg/kg body weight with a 95% confidence interval of 186 to 214 mg/kg.
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 50, 98, 194, 381, and 750  

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 352.4-375.6 g for males and 239.2-254.8 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:
50 mg/kg: 0/5 males; 0/5 females
98 mg/kg: 0/5 males; 0/5 females
194 mg/kg: 3/5 males; 4/5 females (deaths occurred by day 2)
381 mg/kg: 4/5 males; 5/5 females (deaths occurred on day 1)
750 mg/kg: 5/5 males; 5/5 females (deaths occurred on day 1)

Symptoms observed in more than one animal/dose group were decreased activity (98, 194, and 381 mg/kg groups), salivation (98 and 194 mg/kg  

groups), and ataxia and swollen limbs (194 mg/kg group).  Mean body weights of surviving rats increased during the 15-day study period.   

Necropsy findings were negative for all dose groups.

Acute oral toxicity (LD50) values (95% confidence limits), by sex tested:

LD50 (males): 210 (159-261) mg/kg bw
LD50 (females): 175 (131-219) mg/kg bw
LD50 (both sexes): 200 (186-214) mg/kg bw

STUDY RATED BY AN INDEPENDENT REVIEWER.