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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:
Between 7 December 1983 and 7 January 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on composition. Basic data given; the method followed is comparable with OECD 425.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
not specified
Remarks:
in-house quality assurance was in place
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Appearance: clear colourless liquid
Storage: ambient temperature
Batch number: 73/283324

No further details provided

Test animals

Species:
rat
Strain:
other: HC/CFY (remote Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Limited, England
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 80 to 129 g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing
- Housing: individually housed in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum, Laboratory Diet No. 1, Spratt's Rodent Breeding Diet (LAD 1)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 45
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: Between 7 December 1983 and 7 January 1984

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
2.9 ml/kg
Doses:
1.0, 1.26, 1.6, 2.0, 2.5 g/kg
No. of animals per sex per dose:
The study continued until 6 animals per sex had been dosed after reversal of the initial outcome; 11 males and 11 females were
used in total.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: twice daily observations and individual bodyweights of rats were measured on Days 1 (day of dosing), 8 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
LD50 values were estimated by probit analysis, using a slope estimated from background data. The probit model was fitted by
maximum likelihood, with a slope of 8.333 (equivalent to a standard deviation of 0.12 units for the distribution of individual (log.)
tolerance levels). Approximate confidence intervals (95% level) were determined by adding and subtracting 1.96 times the standarderror of the (log.) LD50 estimate.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
95% CL:
1 300 - 1 600
Sex:
female
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
95% CL:
1 000 - 1 600
Mortality:
see: remarks on results including tables and figures
Clinical signs:
Signs in all rats after dosing included piloerection, hunched posture and abnormal gait (waddling). These signs were accompanied
by: lethargy, decreased respiratory rate, ptosis and pallor of the extremities amongst rats at all the dose levels, increased salivation amongst rats dosed at 1.0, 1.26, 1.6 and 2.5 g/kg. Diarrhoea in one female rat treated at 1.26 g/kg and one male at 1.6 g/kg.
Recovery of survivors as judged by external appearance and behaviour was apparantly complete 5 to 7 days after dosing.
Body weight:
All rats that died showed a bodyweight loss. No effects on the survivors.
Gross pathology:
No effects observed in survivors. Autopsy of animals that died revealed congestion of the lungs and pallor of the liver, kidneys and spleen.

Any other information on results incl. tables

Mortality data

0 = survival

1 = death

                                   mortality data on each dosing occasion
 sex  dose (g/kg)  1 10  11 
 m  1.0  0                    
 m  1.26        0    0    0      
 m  1.6      1    1    1    0    
 m 2.0                     1  
 m  2.5    1                  1
 f  1.0  0        0    0        
 f  1.26        1    0    0    1  
 f  1.6      1            1    1
 f 2.0                       
 f  2.5    1                  

Time and number of deaths

 sex  dose (g/kg) No. of deaths                                 Day
       1     2     3     4     5    6 -8
     No. Dosed  0.5 -6 h after dosing  a  b  a  b  a  b  a  b  a  b
 m  1.0  0/1                      
 m  1.26  0/3                      
 m  1.6  3/4        2        1      
 m  2  1/1          1            
m  2.5  2/2        2              
 f  1.0  0/3                      
 f  1.26  2/4      1    1            
 f  1.6  3/3      1  2              
 f  2.5  1/1        1              

a First observation

b Second observation

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute median lethal oral doses (LD50) and their 95% confidence limits were estimated to be:
Males: 1.7 (1.3 to 2.1) g/kg bodyweight
Females: 1.3 (1.0 to 1.6) g/kq bodyweight
According to these results the substance should be classified as Category IV according to OECD-GHS.
Executive summary:

According to an up-and-down procedure male and female rats were administered a single dose of the undiluted test compound ranging from 1.0 to 2.5 g/kg bw. Clinical signs in all rats after dosing included piloerection, hunched posture and abnormal gait (waddling). These signs were accompanied by lethargy, decreased respiratory rate, ptosis and pallor of the extremities amongst rats at all the dose levels, increased salivation amongst rats dosed at 1.0, 1.26, 1.6 and 2.5 g/kg, and diarrhoea in one female rat treated at 1.26 g/kg and one male at 1.6 g/kg. Recovery of survivors as judged by external appearance and behaviour was apparently complete 5 to 7 days after dosing. Body weight of the survivors was not affected, animals that died had decreased bodyweights. Necropsy findings were normal in survivors; in non-survivors these consisted of congestion of the lungs, and pllaor of the liver, kidneys and spleen. The acute median lethal oral doses (LD50) and their 95% confidence limits were estimated to be 1.7 (1.3 to 2.1) g/kg bw for males, and 1.3 (1.0 to 1.6) g/kq bw for females. According to these results the substance should be classified as Category IV according to OECD-GHS criteria.