Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
It was not compliant with GLP.

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 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 2-3kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: undiluted
Details on dermal exposure:
TEST SITE

- Area of exposure: clipped, intact skin of the trunk

REMOVAL OF TEST SUBSTANCE

- Washing (if done): After the contact period, excess fluid was removed.
Duration of exposure:
24 hours
Doses:
8.0, 4.0 and 2.0 ml/kg bw
No. of animals per sex per dose:
5/sex/dose, except only 3 females dosed at 8.0 ml/kg bw (due to insufficient amount of test article)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:  Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period. Body weights were recorded on day 0 (before application), 7 and 14 (prior to termination). 

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:  At necropsy, each animal was subjected to gross pathologic evaluation.
Statistics:
LD50's were calculated by the moving average method (Thompson, 1947) and are based on a 14-day observation period.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3.36 - 4 mL/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to 3259 - 3880 mg/kg bw, based on relative density of 0.97
Mortality:
Most deaths occurred at one to 5 days (one rabbit died at 8 days).   
Clinical signs:
FEMALES: 8 ml/kg bw : sluggishness, unsteady gait at 3 minutes; marked sluggishness at 15 minutes; prostration at 2 hours. 4 ml/kg bw: Sluggishness, unsteady gait, lacrimation at 17 minutes; unkempt appearance, brown perianal discharge at 1 day. Survivors recovered at 2 days. Prostration in one at 2 days. 2 ml/kg bw: sluggishness at 3.5 hours; unkempt appearance, mild red perinasal discharge at 1 day. Recovery at 2 days.

MALES: 8 ml/kg bw : Immediate signs of discomfort (intense struggling, vocalization); sluggishness to prostration at 1 day. Recovery of survivor at 3 days. 4 ml/kg bw: immediate signs of discomfort; sluggishness, unsteady gait at 1 day. Recovery of survivors at 2 to 3 days. 2 ml/kg bw; immediate signs of discomfort; unsteady gait at 1 days. recovery in 2 days. Emaciation in 1 at 7 days (dead at 8 days).
Body weight:
No data available.
Gross pathology:
At necropsy, lungs appeared red and mottled in animals that died.  A few livers were mottled or had red or white foci in animals that died.  No remarkable findings were noted in survivors.  
Other findings:
- Other observations: Skin reaction included erythema, ecchymosis and desquamation. Discomfort, sluggishness, unsteady gait, and prostration were observed.  Survivors recovered at 2 to 3 days.

Any other information on results incl. tables

Table 1: Number of animals dead and time range within which mortality occurred

 

Dose
(mg/kg
bw)

Mortality (# dead/total)

Time range of deaths (days)

Male

Female

Combined

8

 4/5

 3/3

 7/8

 1,2,3

4

 2/5

 3/5

5/10 

 3,4,5

2

 2/5

 1/5

 3/10

 3,8

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Acute dermal LD50 (rabbit) values of 3.36 ml/kg bw for females and 4 ml/kg bw for males were determined in a reliable study conducted according to an appropriate test protocol. The study was not in compliance with GLP.