3,3'-oxybis(ethyleneoxy)bis(propylamine)

Endpoint summary

Description of key information

Skin, rabbit, similar to OECD 404: corrosive (1984, no GLP, reliability 2)
Eye: corrosive 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

short exposure period (3 min and 1 hour); occlusive coverage; short observation period (72 hours); non-GLP)

Principles of method if other than guideline:

BASF-test (short-term test): The undiluted test substance was applied 3 min and 1 h to the intact rabbit skin under an occlusive dressing. Scoring according to Draize was carried out after patch removal and after 24, 48 and 72 h.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4,7,10-Trioxatridecan-1,13-diamin
- Physical state/appearance: yellowish liquid
- Purity: min 95%
- Expiration date of the lot/batch: July 1985

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach/Main, FRG
- Weight at study initiation: mean males 2.69 kg
- Housing: single housing in stainless steel cages (floor area 40 cm x 51 cm)
- Diet: ca. 130 g Ovator Solikanin 4 mm (Muskator-Werke, Düsseldorf, FRG) per animal per day
- Water: ca. 250 mL tap water per animal per day
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: ca. 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:

3 minutes and 1 hour

Observation period:

72 hours

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm skin area on the upper third of the back or flank
- Type of wrap if used: not specified

REMOVAL OF TEST SUBSTANCE
- Washing: with Lutrol (concentrated) and Lutrol/water (1:1)
- Time after start of exposure: 3 minutes or 1 hour

SCORING SYSTEM: according to Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.8

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: 3 minutes occlusive exposure

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: 3 minutes occlusive exposure

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 1 hour occlusive exposure

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.9

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: 1 hour occlusive exposure

Irritant / corrosive response data:

3 min exposure: erythema of max. grade 2, not fully reversible within the 72-h observation period; edema of grade 1 in one animal, fully reversible within 48 h
1 h exposure: comprehensive erythema and edema; necrosis in all animals from 24 h after application of the TS onwards, full-thickness necrosis in all animals 72 h after application of the TS, finding macroscopic-pathologically confirmed 72 h after application of the TS

Table 1: Irritation scores:

Timepoint	Animal No.	Intact skin		Symptoms
		Erythema	Edema
3 minutes exposure, occlusive
3 min	1	1	0
	2	1	1
	3	1	0
24 h	1	0	0
	2	2	1
	3	1	0
48 h	1	0	0
	2	2	0
	3	0	0
72 h	1	0	0
	2	2	0
	3	0	0
Mean 24, 48, 72 h	1	0	0
Mean 24, 48, 72 h	2	2	0.3
Mean 24, 48, 72 h	3	0.3	0
Mean 24, 48, 72 h	1, 2, 3	0.8	0.1
1 hour exposure, occlusive
1 h	1	2	3	Overlapping erythema and edema, haemorrhagic
	2	3	2
	3	3	3
24 h	1	4	2	Necrosis, overlapping edema
	2	4	2
	3	4	2
48 h	1	4	2	Necrosis, overlapping edema
	2	4	2
	3	4	2
72 h	1	4	2	Necrosis, overlapping edema, full-thickness necrosis macroscopic-pathologically confirmed
	2	4	1
	3	4	2
Mean 24, 48, 72 h	1	4	2
Mean 24, 48, 72 h	2	4	1.7
Mean 24, 48, 72 h	3	4	2
Mean 24, 48, 72 h	1, 2, 3	4	1.9

 

 

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

A 1-hour occlusive treatment with the unchanged test substanced caused skin corrosion in rabbits.

Executive summary:

In this short-term test (non-GLP, reliability 2), the undiluted test substance was applied 3 min and 1 h to the intact rabbit skin (3 males, Vienna White) under an occlusive dressing. After exposure, the substance was washed with with Lutrol (concentrated) and Lutrol/water (1:1). Scoring according to Draize was carried out after patch removal and after 24, 48 and 72 h. An exposure duration of 3 min caused erythema of max. grade 2 (not fully reversible) and edema of grade 1 in one animal (fully reversible within 48 h). Extension of the exposure time provoked severe skin reactions. After 1 h of treatment, comprehensive erythema and edema, as well as necrosis was observed in all animals from 24 h after application of the test substance onwards. A full-thickness necrosis in all animals was macroscopic-pathologically confirmed at the end of the study.

Based on this study finding, the test substance is corossive (Cat. 1B) to the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The skin irritating/corrosive potential of the test substance was analysed in rabbits in an in-house (short-term) test (BASF, 1984) similar to OECD guideline 404. A 2.5 x 2.5 cm cloth coated with the test substance was applied 3 min and 1 h to the intact rabbit skin under an occlusive dressing. Scoring according to Draize was carried out after patch removal and the severity was noted 24, 48 and 72 h after substance application.

The following observations were made:

3 min exposure: erythema of max. grade 2, not fully reversible within the 72-hour exposure period; edema of grade 1 in one animal, fully reversible within 48 hours. The beginning reversibility of the irritating effects seen at the 72 h reading indicates that no full-thicknesss necrosis would have occurred after a prolonged observation period.

1 hour exposure: comprehensive erythema and edema; necrosis in all animals from 24 hours after application (i.e. of the test substance) onwards, full-thickness necrosis in all animals 72 hours after application, finding macroscopic-pathologically confirmed 72 hours after application.The study is classified as acceptable (key study).

In addition, in a skin irritation study (Union Carbide Corp., 1992) on rabbits it was demonstrated that the test substance exhibited corrosive properties, since full-thickness necrosis was noted after 1-hour dermal exposure to the test substance.

Smyth et al. (1969) reported the test substance as ‘highly irritating’ to rabbit skin. Both references were flagged as ‘supporting study.’

 

Eye irritation:

Eye injury in rabbits was investigated by Smyth et al. (1969) using a 10-grade ordinal series and was based upon the degree of corneal necrosis that resulted from instillation of various volumes and concentrations of a chemical. Grade 1 indicates at most a very small area of necrosis resulting from 0.5 mL of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 mL, and Grade 10 indicates a severe burn from 0.5 mL of a 1% solution in water or propylene glycol.Corneal injury in rabbits were classified as Grade 8 (= excess of 5 % solution gives injury of up to 5.0 points (15 % gives over 5.0), see Carpenter, C.P. & Smyth, H.F.: Chemical Burns of the Rabbit Cornea.Am. J. Ophthal. 29: 1363 (Nov. 1946)). The test substance was deemed as ‘highly irritating’. This publication is classified as acceptable.

 

Justification for selection of skin irritation / corrosion endpoint:
Most reliable study (key study).

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive based on skin corrosivity

Justification for classification or non-classification

In the skin irritation study, the test substance induced necrosis in all tested animals following a 1 hour exposure period. Thus, the substance is considered to be classified for skin corrosion Cat. 1B under Regulation (EC) No. 1272/2008. As the substance is skin corrosive, this leads to its classification as serious eye damage Cat. 1.