N,N,N',N'-tetramethylhexamethylenediamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Jan 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

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

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethylhexamethylenediamine

EC Number:

203-842-9

EC Name:

N,N,N',N'-tetramethylhexamethylenediamine

Cas Number:

111-18-2

Molecular formula:

C10H24N2

IUPAC Name:

[6-(dimethylamino)hexyl]dimethylamine

Specific details on test material used for the study:

- 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 or test system 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:

yes, concurrent no treatment

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

Results

Results 1

Irritation parameter:

other: necrosis

Basis:

mean

Time point:

24/48/72 h

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

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

1 hr exposure

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 72 hrs)

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 min exposure

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 72 hrs)

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

1 hr exposure

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 72 hrs)

Remarks on result:

other: extending beyond the area of exposure; finding confirmed by gross-pathological examiniation

Results 5

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 min exposure

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 72 hrs)

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) based on GHS criteria

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.