Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older published study and original report; guideline comparable with limited reporting details but sufficient for the assessment of toxicity and classification

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Range-finding toxicity data List V
Author:
Smyth HF, Carpenter CP, Weil CS, Pozzani UC
Year:
1954
Bibliographic source:
AMA Archives of Industrial Hygiene and Occupational Medicine 10(1): 61-68
Reference Type:
study report
Title:
Unnamed
Year:
1953
Report Date:
1953

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The study was conducted according to the one-day cuff method of Draize et al (1944), and is generally similar to OECD 402.
GLP compliance:
no
Remarks:
older proprietary study; pre-dates GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Hexaonic acid, ε-lactone. Obtained from S. Charleston, batch number 242 RD 89.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
The animals were male New Zealand giant albino rabbits, weighing 2.5 to 3.5 kg and 3 to 5 months of age..

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The fur of the entire trunk was closely clipped, and the substance was placed in contact with the skin so as to cover about 10% of the body surface. The substance was held in place with an occlusive impervious plastic film (polyethylene). After 24 hours exposure to the substance, the film and test substance was removed.
Duration of exposure:
24 hours
Doses:
Doses applied were 5000 and 10000 mg/kg bw.
No. of animals per sex per dose:
4 males/dose
Control animals:
no
Details on study design:
The rabbits were observed for 14 days after removal of the test substance. Necropsies were performed.
Statistics:
The LD50 with limits of ± 2 standard deviations (95% confidence limits) was calculated by the Thompson method

Results and discussion

Preliminary study:
None
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
5.99 mL/kg bw
Based on:
test mat.
95% CL:
4.27 - 8.42
Remarks on result:
other: Equivalent to 6400 mg/kg bw using a relative density of 1.07
Mortality:
Deaths occurred at 10000 ml/kg bw (4/4) and at 5000 ml/kg bw (1/4) on Day 1 or 2.
Clinical signs:
Skin erythema was produced, which may or may not result in necrosis and desquamation.
Body weight:
One survivor at 5000 mg/kg bw lost weight (58 g; ~2.4% initial weight) over the study period.
Gross pathology:
Autopsies revealed congested haemorrhagic lungs, and extremely congested livers.
Other findings:
No other findings reported.

Any other information on results incl. tables

Dose level (ml/kg bw)

Deaths

Day of death

10000

4/4

1-2

5000

1/4

2

The acute dermal LD50 was calculated to be 5.99 ml/kg bw; this is equivalent to 6400 mg/kg bw using a relative density of 1.07.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 was 5.99 (4.27 -8.42) ml/kg bw; calculated to be equivalent to 6400 (4570 -9000) mg/kg bw.
Executive summary:

The acute dermal toxicity of ε-caprolactone was determined in male New Zealand White rabbits (4 per group). The test substance was applied to the clipped skin of the trunk, covering approximately 10% of the body surface. The test substance was held in place for 24 hours using an impervious plastic film. After removal of the dressing, the rabbits were observed for 14 days for mortality. Deaths occurred at 10000 ml/kg bw (4/4) and at 5000 ml/kg bw (1/4). Skin erythema was produced, and autopsies revealed congested haemorrhagic lungs, and extremely congested livers. The acute dermal LD50 was 5.99 (4.27 -8.42) ml/kg bw; calculated to be equivalent to 6400 (4570 -9000) mg/kg bw.