Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-06-08 to 2010-08-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Lot No. 10021006
clear liquid, odor of amine,
purity: > 99%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Strain: Sprague-Dawley (Crl:CD(SD)), SPF
- Sex, number, age and body weight range (at receipt)
12 males, 7 weeks old, 197.9 - 210.7 g
12 females, 8 weeks old, 198.8 - 212.1 g
- Sex, number, age and body weight range (on administration)
10 males, 8 weeks old, 263.5 - 288.9 g
10 females, 9 weeks old, 215.6 - 235.9 g
- All animals were observed for general condition and clinical signs daily and body weights were on Day 7 after receipt. All animals were quarantined for 3 days, and acclimated for 4 days.
- Animal husbandry:
Type & size of a cage: stainless wire mesh cages, 260Wx350Dx210H (mm)
Number of animals per cage: one animal/cage (during the study)
Temperature: 21.0 - 23.8 °C
Relative humidity: 40.3 - 53.4%
Air changes: 10 - 15 clean, fresh, filtered air changes per hour
Lighting: 12 hours light/dark
Intensity of illumination: 150 - 300 Lux
- Feed:
Type: Pelleted rodent chow
Method: The diet was placed in feeders and provided ad libitum
- Water:
Type /method: Public tap water was filtered and irradiated; provided ad libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Method of administration:
The subscapular dorsa surface (approx. 5 cm x 6 cm) of each animal`s back was clipped with an electric clipper approx. 24 hours prior to dosing. 4 cm x 5 cm of these shaved areas were designated as the treated sites. After the treatment of the test substance to lint tape, the treated sites were covered with lint tape and plastic film. Each animals back was over-wrapped with Soft Cloth Tape with Liner. At the end of a 24-hour exposure period, lint tape, plastic film and Soft Cloth Tape with Liner were removed and any residual test substance was removed using adsorbent cotton moistened with tepid water. The shaved treated sites of the control animals were dressed in the same manner as the treated animals.
Duration of exposure:
24 hours
Doses:
The dose level of 2,000 mg/kg was selected for this study, which was expected to show low toxicity.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Details on study design:
Parameters Evaluated:
- Clinical signs: All animals were observed for mortality, general condition and clinical signs (time onset, severity and recovery) for 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once saily thereafter for 14 days (Days 1 to 14).
- Body weights: Body weights were recovered once on Day 0 prior to treatment on Day 3 and 7 and 0n the day of necropsy, day 14.
- Necopsy: On Day 14, all surviving animals were anesthetized with CO2 and exsanguinated from the abdorminal aorta. Complete gross postmortem examinations were performed on all animals in the study.
- Histopathology: In necropsy findings, crust was observed on the treated sites of all animls in the 2,000 mg/kg dosing group. Therefore, histopathological examinations were performed.
Statistics:
Statistical analysis: using SAS Programm;
Body weights: Folded-F test for homogeneity of variance (significant level: 0.05);
Student t-test was employed on homogeneous data (significance level: 0.05);
Aspin-Welch t-test was employed for heterogeneous data (significant level: 0.01)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities
Mortality:
No mortality was observed at 2,000 mg/kg treatment throughout the course of the study.
Clinical signs:
On the treated sites at 2,000 mg/kg treatment, discoloration of skin (black) in all males and females and crust formation in two males and five females were observed on Days 1 and/or 2. In addition, discolorations of skin and crust formations were observed in all males and females from Days 3 to 14 after dosing. Scar was observed on the treated sites of three males and females at 2,000 mg/kg treatment on Days 11 to 14.
Body weight:
Normal body weight gains were observed in all animals at 2,000 mg/kg treatment.
Gross pathology:
Necropsy and histopathological findings:
Crust were observed on the treated sites of all animals at 2,000 mg/kg treatment. In histopathological findings, scar as mild to moderate was observed on the treated sites of all animals.
Other findings:
No other findings

Any other information on results incl. tables

No further information

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Based on the results of this study, the acute toxicity of isophorone diamine after dermal application to male and female rats is low: the LD50 value was determined to be > 2000 mg/kg bw.
Executive summary:

This study was conducted to assess the potential toxicity of the test substance isophorone diamine, following a single dermal treatment to Sprague-Dawley rats.

All animals at 2,000 mg/kg treatment survived the duration of the study.

Discoloration of skin and crust formation from Days 1 to 14 after dosing and scar from Days 11 to 14 were observed on the treated sites of all animals at 2,000 mg/kg treatment. These were considered to be test substance-related effects. No test substance-realted affected on body weights were observed.

In necropsy findings, crust was observed on the treated sites of all animals at 2,000 mg/kg treatment. In histopatholocical findings, scar as mild to moderate was observed on the treated sites of all animals. These were considered to be skin wounds caused by the test substance.

Based on the results of this study, Acute toxicity of isophorone diamine, the dermal LD50 was > 2,000 mg/kg in male and female rats.