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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted similar to OECD guideline, no GLP (GLP was not mandatory when study was done)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1981-05-12)
GLP compliance:
no
Remarks:
when study was done GLP was not mandatory

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N, N, N', N'-Tetramethyl-1,6-hexanediamine
- Analytical purity: 97.5 %
- Expiration date of the lot/batch: stable until 1984-01
- Impurities (identity and concentrations): N,N',N'-Trimethyl-1,6-hexanediamine 2%

Test animals

Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Housing: single housing in cages made of stainless steel with mire mesh walk floor, floor area: 40x51 cm, no bedding in the cages
- Diet (e.g. ad libitum): Ovator Solikanin 4mm, Muskator-Werke, Düsseldorf, Germany
- Water (e.g. ad libitum): fully demineralized water (monday to friday) and tap water (saturday/ sunday)
- Acclimation period: 8 days before study begin, same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 26
- Humidity (%): 30- 70
- Air changes (per hr): 15- 20 times
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL (test patch dipped in undiluted substance)

Duration of treatment / exposure:
3 min, 1 hr
Observation period:
72 hrs
reading time points: 30-60 min after removal of test patches; 24, 48 and 72 hrs after beginning of the application
Number of animals:
2 male 1 female animal
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of exposure period with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 3 min, 1 hr

SCORING SYSTEM: Draize scoring system (Draize et al. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity 46-59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Remarks on result:
other: In experiments with 1 hr exposure time: after 72 hrs deep necrosis in all animals; in experiments with 3 min exposure time: marked necrosis after 72 hrs
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 72 hrs)
Remarks on result:
other: 60 min. exposure time
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 72 hrs)
Remarks on result:
other: 3 min. exposure time
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
2.7
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 72 hrs)
Remarks on result:
other: 60 min. exposure time, extending beyond the area of exposure; finding confirmed by gross-pathological examiniation
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
1.7
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 72 hrs)
Remarks on result:
other: 3 min. exposure time
Irritant / corrosive response data:
Necrosis was seen in both experiments (3 min and 1 hr exposure time) in all animals after 24 hrs observation time. After 72 hrs a marked necrosis could be detected for experiments with 3 min exposure time, and a deep necrosis for experiments with 60 min exposure time.
Severe to very severe erythema were seen in all animals over all reading time points (24, 48, 72 hrs) in both experiments (exposure time 1 hr and 3 min). Consequently this effect is not reversible within the given timepoints.
Clearly visible edema were seen in all animals after 24 and 48 hrs in experiments with 3 minutes exposure time. After 72 hrs edema score still very weak edema were seen. Consequently this effects is not reversible within 72 days. The edema extend beyond the exposed area. The edema were confirmed by gross-pathological examinations. In tests with an exposure time of 60 min more severe edema (grade 3 moderate to severe edema) were seen after 24 and 48 hrs in all animals. After 72 hrs the edema were reduced to grade 2 (clearly visible). Again the edema covered an area larger than the exposure size. Within the observation time all edema effects are not reversible.

Any other information on results incl. tables

Animals were sacrificed after 3 days.

Table 1: Skin irritation score for exposure time of 3 and 60 minutes

 

3 minutes exposure time

60 minutes exposure time

Readings

Animal

Erythema
 score

Edema
 score

Animal

Erythema
 score

Edema
 score

24 hrs

1

4

2

1

4

3

 

2

4

2

2

4

3

 

3

4

2

3

4

3

48 hrs

1

4

2

1

4

3

 

2

4

2

2

4

3

 

3

4

2

3

4

3

72 hrs

1

4

1

1

4

2

 

2

4

1

2

4

2

 

3

4

1

3

4

2

Mean

1

4

1.7

1

4

2.7

per animal

2

4

1.7

2

4

2.7

24, 48, 72 hrs

3

4

1.7

3

4

2.7

Mean
(24, 48, 72 hrs)

 

4

1.7

 

4

2.7

Applicant's summary and conclusion

Interpretation of results:
Category 1A (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was shown to be corrosive under the conditions of this study.
Executive summary:

A test was done for assessing the corrosive or irritating potential of the test substance.

The test was done equivalent to OECD guideline 404 (adopted 1981 -05 -12) under occlusive conditions with 2 different exposure times (3 min and 1 hr). Two male and 1 female white vienna rabbits were tested per application .

After 24 hrs (1 st observation time point) necrosis was seen in all animals in both experiments. After 72 hrs a deep necrosis could be seen for experiments with longer exposure time (1 hr) and a marked necrosis for the test with shorter (3 min) exposure time. Severe to very severe erythema were seen in all animals over all reading time points (24, 48, 72 hrs) in both experiments (exposure times 1 hr and 3 min). These effects were not reversible within observation period. Additionally in both experiments edema were seen. For tests with shorter exposure time the edema were of grade 2 for 24 and 48 hrs and decrease to score 1 after 72 hrs. For tests with longer exposure time moderate to severe edema were detected after 24 and 48 hrs. These effects decreased to grade 2 (clearly visible) for tests after 72 hrs. Due to the irreversible damage to the skin, the compound is to be considered as corrosive.