Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1966
Report Date:
1966

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Method: other: Contract laboratory protocol
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Tradename Neodol 45

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: Young adults
- Weight at study initiation: 2.5-3.5 kg
- Fasting period before study:
- Housing: standard laboratory cages during pre-dosing, dosing, and post -dosing observation periods.
- Diet: ad libitum
- Water: ad libitum


Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: 50% w/v solution of Neodol 45 in Dowanol DPM
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: 10% of body surface clipped for application.
- Type of wrap if used: plastic film, securely affixedc with masking tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported

VEHICLE
- Concentration (if solution): 50%
Duration of exposure:
24 hours
Doses:
3.038, 4.556, 6.834 and 10.25 g/kg
No. of animals per sex per dose:
2M, 2F
Control animals:
no
Details on study design:
- Duration of observation period following administration: not reported
- Frequency of observations and weighing: Periodic examination for mortality and clinical signs  during exposure then daily thereafter including monitoring for skin  irritation at the application site.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
The LD50 was calculated using the methods of Weil  1952 and Thompson et al, 1947 and 1952.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 180 mg/kg bw
Mortality:
- Time of death: 4 rats died during the exposure period, 3 others died  between days 3 and 6.
Clinical signs:
General weakness was observed in 10 rabbits within 24  hours with recovery between days 2 and 5. Anorexia was observed in all  rabbits, recovery of survivors  occurred between days 5-7. Iritis was  observed 10 rabbits within 24 hours reversing between days 2 and 4.
Body weight:
Not reported.
Gross pathology:
There were no remarkable gross pathological findings  amongst survivors. In premature decedents hyperaemic lungs were observed  in all animals. Thickening of skin at the application site was observed  in most decedents.
Other findings:
POTENTIAL TARGET ORGANS: None identified.
APPLICATION SITE: Erythema (mild -severe) was observed at the application  site within 24 hours, with recovery in survivors by day 8. Within 1-2  days there was drying of the site and subsequent fissuring with loss of  the uppermost layers which continued  throughout the observation period.

Any other information on results incl. tables

Table 1: Number of animals dead  

Dose
(mg/kg
bw)

Mortality (# dead/total)

Male

Female

Combined

3038

0/2 

0/2

 0/4

4556

1/2

 0/2

 1/4

6834

 0/2

 2/2

2/4 

10250

 2/2

 2/2

4/4 

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The rabbit dermal LD50 for Neodol 45 as a 50% solution in Dowanol DPM was 6.18 g/kg. Skin irritiation was observed at the application site of all animals persisting until the end of the observation period. Clinical signs of toxicity were generalised weakness and anorexia. Iritis was reported during exposure peristing for several days. Findings at gross necropsy were unremarkable for survivors.