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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:
June 8, 1983 to July 19, 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 level administered.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
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:
Methods equivalent to OECD Guideline 401
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Carbonyl nickel powder
- 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
- Physical state: Solid (powder)
- All other details on test material 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: Not reported
- Weight at study initiation: Mean fasted body weights ranged from 214.0-246.2 g for males and 196.6-209.8 g for females. 
- Fasting period before study: Food withheld on night prior to dosing
- Housing: Individually housed in wire mesh bottom cages
- 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
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: June 15, 1983 To: June 30, 1983

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: mineral oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Weighed 85 grams of test material (50% w/v)
- Amount of vehicle (if gavage): 170 ml
- Justification for choice of vehicle: Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: Not reported

DOSAGE PREPARATION (if unusual): Weighed 85 grams of test material, Q.S. 170 ml with vehicle

CLASS METHOD (if applicable): Not applicable
Doses:
Animals received a single oral dose of 4000, 4899, 6000, 7348, or 9000 mg/kg
No. of animals per sex per dose:
10 (5 males and 5 females)
Control animals:
yes
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.  

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Days 0, 8, and 15 (or at death)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight measurements were conducted
Statistics:
Not reported

Results and discussion

Preliminary study:
The range finding study was conducted using 2 male and 2 female rats at dose levels of 100, 266, 707, 1880, and 5000 mg/kg.
Mortality was observed for 8 days. One animal died on day 4 at the 5000 mg/kg dose group.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 9 000 mg/kg bw
Mortality:
Cumulative mortality observed (number of mortalities observed/total number of animals tested), by nominal dose administered:
4000 mg/kg: 0/5 males; 0/5 females
4899 mg/kg: 0/5 males; 0/5 females
6000 mg/kg: 0/5 males; 0/5 females
7348 mg/kg: 1/5 males; 0/5 females (death occurred on day 5)
9000 mg/kg: 0/5 males; 0/5 females
Clinical signs:
The only symptom observed in more than one animal/dose group was diarrhea in the 9000 mg/kg group.
Body weight:
Mean body weights of surviving rats increased during the 15-day study period.
Gross pathology:
Necropsy findings were generally negative for all dose groups.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not reported
- Other observations: none examined

Applicant's summary and conclusion

Conclusions:
Based on the data obtained from this study, the acute oral LD50 for male and female rats was found to be greater than 9000 mg/kg body weight.
Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.

Robust Summary for FDRL (1983):


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.  A  suspension of the test substance was prepared in mineral oil.

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 4000, 4899, 6000, 7348, and  

9000 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 214.0-246.2 g for males and 196.6-209.8 g for females.  Surviving animals were sacrificed on day 15  

and all animals were necropsied and examined for abnormalities.

Cumulative mortality observed (number of mortalities observed/total number of animals tested), by nominal dose administered:
4000 mg/kg: 0/5 males; 0/5 females
4899 mg/kg: 0/5 males; 0/5 females
6000 mg/kg: 0/5 males; 0/5 females
7348 mg/kg: 1/5 males; 0/5 females (death occurred on day 5)
9000 mg/kg: 0/5 males; 0/5 females

The only symptom observed in more than one animal/dose group was diarrhea in the 9000 mg/kg group.  Mean body weights of surviving rats increased  

during the 15-day study period.  Necropsy findings were generally negative for all dose groups.

Based on the lack of observed, dose-related mortality, the acute oral LD50 for male and female rats was found to be >9000 mg/kg bw.