Amines, polyethylenepoly-, triethylenetetramine fraction

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 4-19,1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

stability/purity not reported

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Amines, polyethylenepoly-, triethylenetetramine fraction

EC Number:

292-588-2

EC Name:

Amines, polyethylenepoly-, triethylenetetramine fraction

Cas Number:

90640-67-8

Molecular formula:

C6H18N4, C8H20N4

IUPAC Name:

Amines, polyethylenepoly-, triethylenetetramine fraction

Test material form:

liquid

Specific details on test material used for the study:

- Amount received: 662.77 g (gross weight)
- pH: 8 (litmus paper)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Denver, PA
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 2.325-2.607 kg
- Housing: Rabbits were housed individually in cages sized in accordance with the ''Guide for the Care and Use of Labolatory Animals'' of the Institute of National Research Council.
- Diet: Purina Lab Rabbit Chow (H.F.) ad libitum
- Water:fresh tap water, ad libitum
- Acclimation period: minimum 5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3 (63°-73°F)
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light):12h light, 12h dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL/site (6 cm²)

Duration of treatment / exposure:

The test article was administrated once per site:
3 min, 60 min, 4h, 24 h

Observation period:

14d

Number of animals:

Six (6) :3♂ and 3♀

Details on study design:

TEST SITE
- Area of exposure: 5 sites on the dorsal trunk
- Type of wrap if used: impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): by using water and a gauze
- Time after start of exposure: 3 min, 60 min, 4h, 24h

SCORING SYSTEM:
Draize Evaluation of Dermal Irritation, Primary Irritation Index

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

6 animals

Time point:

other: 4h exposure

Score:

8

Max. score:

8

Reversibility:

not reversible

Remarks on result:

other: necrosis at 24 hour reading time point in 5/6 animals

Results 2

Irritation parameter:

erythema score

Remarks:

3-minute exposure

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: necrosis in all animals

Results 3

Irritation parameter:

edema score

Remarks:

3-minute exposure

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: necrosis in all animals

Irritant / corrosive response data:

animals have been exposed for 60min, 4h, and 24h. All animals scored 4 (necrosis) for erythema and edema immediately after unwrapping.
Severe erythema and severe edema remained present in all animals at all observation periods during the study (up to 14 days).

Any other information on results incl. tables

 

Animal No.	Sex	Body Weight Initial (kg)	Body weight Final (kg)
1	M	2.405	2.752
2	M	2.514	2.707
3	M	2.387	2.673
4	F	2.591	2.847
5	F	2.607	2.903
6	F	2.325	2.495

Table 1: 3-minute exposure
Rabbit/sex sex	0 hours*		24 hours		48 hours		72 hours		Day 4 - 14
	erythema	edema	erythema	edema	erythema	edema	erythema	edema	erythema	edema
1M	2	0	4N	4	4N	4	4N	4	4N	4
2M	1	0	4N	4	4N	4	4N	4	4N	4
3M	2	0	4N	4	4N	4	4N	4	4N	4
4F	1	0	4N	4	4N	4	4N	4	4N	4
5F	0	0	1	0	2	0	4N	4	4N	4
6F	2	0	4N	4	4N	4	4N	4	4N	4
mean	1.3	0	3.5	3.3	3.7	3.3	4	4	4	4
Mean erythema 24/48/72h		3.7
Mean edema 24/48/72h		3.5
*: immediately after unwrap N = Necrosis

 

Table 2: 60-minute, 4-hour and 24-hour exposure
Rabbit/sex sex	0 hours*		24 hours		48 hours		72 hours		Day 4 - 14
	erythema	edema	erythema	edema	erythema	edema	erythema	edema	erythema	edema
1M	4N	4	4N	4	4N	4	4N	4	4N	4
2M	4N	4	4N	4	4N	4	4N	4	4N	4
3M	4N	4	4N	4	4N	4	4N	4	4N	4
4F	4N	4	4N	4	4N	4	4N	4	4N	4
5F	4N	4	4N	4	4N	4	4N	4	4N	4
6F	4N	4	4N	4	4N	4	4N	4	4N	4
mean	4	4	4	4	4	4	4	4	4	4
Mean erythema 24/48/72h		4.0
Mean edema 24/48/72h		4.0
*: immediately after unwrap N = Necrosis

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS Category 1B (H314) according to Regulation (EC) No 1272/2008

Conclusions:

The test article was considered to be severe dermal irritant at both 4 and 24 hour exposures.
The Dermal Irritation Toxicity Category is Class I (corrosive).
The DOT Packing Group Classification is Class I (corrosive at less than 3 min).
Primary Dermal Irritation Index at 4h and 24h exposure=8.00 (according to Draize scoring system).
No reading time point at 1 hour after 3-minute exposure was available in order to definetly find a conclusion on subcategory 1A or 1B. Since after immediate observation after 3-minute exposure well-defined erythema (score 2) was found in 3 out of 6 animals it is not assumed that after on hour necrosis would have been formed. Therefore, a classification category 1B is considered.

Executive summary:

The test substance was examined undiluted for skin irritation in groups of 3 rabbits per sex. The test material was applied (semi-occlusive) directly on the intact and abraded skin sites. The skin was abraded using a burred needle, the abrasion penetrated the stratum corneum, but not the derma. The test article was administrated once per site for 3 min, 60 min, 4h, or 24 h. Necrosis was observed after 3 min exposure. The animals that had been exposed for 60 min, 4 h, or 24h scored 4 (necrosis) for erythema and edema immediately after unwrapping. Severe erythema and severe edema remained present in all animals at all observation periods during the study (up to 14 days).