Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
1973
Report Date:
1973
Reference Type:
publication
Title:
Comparative acute toxicity and primary irritancy of various classes of amines
Author:
Myers RC, Ballantyne B
Year:
1997
Bibliographic source:
Tox Subst Mechanisms 16:151-194

Materials and methods

Principles of method if other than guideline:
24 hr dosing period followed by a 14 day observation period
GLP compliance:
no
Test type:
other: 24 hr dermal dosing period followed by a 14 day observation period
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
- Age at study initiation: 3 - 5 month
- Weight at study initiation: 2.0 - 3.0 kg
- Diet and water: Non-fasted animals are maintained on appropriate Rockland diets and water ad lib except during period of manipulation or confinement.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Male albino rabbits, 3 to 5 months of age, are immobilized during the 24-hour contact period with the compound retained unter impervious sheeting on the clipped intact skin of the trunk. Thereafter, excess fluid is removed to prevent ingestion.
Duration of exposure:
24-hours
Doses:
16000, 8000 or 4000 mg/kg
No. of animals per sex per dose:
4 male rabbits/dose level
Control animals:
not specified
Details on study design:
Dosage intervals differ by a factor of 2 in a geometric series.
Statistics:
LD50 was calculated by the moving average method based on a 14-day observation period.

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
8 000 mg/kg bw
Mortality:
Rabbits given 16000, 8000 or 4000 mg/kg resulted in 4/4, 2/4 and 0/4 (dead/dosed),
Clinical signs:
Skin irritation consisting of erythema and necrosis where pressure of stocks was present, was observed at all dose levels.
Body weight:
8000 mg/kg in survivors: One rabbit gained 318 g while other rabbit lost 143 g over 14 day observation period.
4000 mg/kg: All rabbits gained weight during 14 day observation period. Weight gain ranged from 140 to 313 g.
Gross pathology:
Gross pathology consisted of congestion of lungs, livers, spleens and kidneys, mottled livers and opaque stomachs.
Other findings:
no data

Any other information on results incl. tables

Rabbits given 16000, 8000 or 4000 mg/kg resulted in 4/4, 2/4 and 0/4 (dead/dosed), respectively. Skin irritation consisting of erythema and necrosis where pressure of stocks was present, was observed at all dose levels. Gross pathology consisted of congestion of lungs, livers, spleens and kidneys, mottled livers and opaque stomachs.

Applicant's summary and conclusion

Executive summary:

DIPA was applied dermally for 24 hours at doses of 4000, 8000 or 16,000 mg/kg to the intact skin of groups of 4 male rabbits. All rabbits from the 16,000 mg/kg group died while 2 of 4 rabbits from the 8000 mg/kg group died within the 14-day observation period. The dermal LD50 was determined to be 8000 mg/kg using the moving average method of statistical analysis.