Poly(oxy-1,2-ethanediyl), α-[2-(dide- cylmethylammonio)ethyl]- .omega.- hydroxy-, propanoate (salt) (Bardap 26)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July - September 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

bis(decyl)(2-hydroxyethyl)methylazanium propanoate

EC Number:

619-057-3

Cas Number:

94667-33-1

Molecular formula:

C29 H62 N O4 . C3 H5 O2

IUPAC Name:

bis(decyl)(2-hydroxyethyl)methylazanium propanoate

Constituent 2

Reference substance name:

alpha.-[2-(Didecylmethylammonio)ethyl]-.omega.-hydroxy-poly(oxy-1,2-ethanediyl) propionate

IUPAC Name:

alpha.-[2-(Didecylmethylammonio)ethyl]-.omega.-hydroxy-poly(oxy-1,2-ethanediyl) propionate

Constituent 3

Reference substance name:

N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate

IUPAC Name:

N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate

Constituent 4

Reference substance name:

Bardap 26

IUPAC Name:

Bardap 26

Details on test material:

The test material was Bardap 26 described as a clear, yellow liquid. The test substance was stored at 22°C in the dark in a fume hood.
The deviation in composition of the old test material to the current specifications is considered not to have any impact on the outcome of the study.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The animals were 3-5 month old New Zealand White rabbits obtained from Hoechst AG, Kastengrund, Germany. The rabbits weighed 2.2-3.6 kg. The animals were housed individually, temperature was maintained at 20 ± 3°C and relative humidity was maintained at 50 ± 20% with a 12 hour light/dark cycle. The rabbits were fed Altromin 2123 Haltungsdiat - Kaninchen ad libitum, and provided with deionised chlorinated water ad libitum.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml undiluted test substance/site

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

14 days

Number of animals:

3 per exposure period

Details on study design:

On the day prior to administration, the dorsal area and the trunk of each animal was clipped free of fur. Only animals with intact skin were selected for the test.
On the day of dosing, a wound plaster with a 2.5 x 2.5 cm pulp patch (Beiersdorf AG, Hamburg) was fixed on the prepared skin site of each animal. 0.5 ml of the undiluted test substance was administered under the plaster. For animals with 1- and 4-hour exposures the test area was covered with a semi-occlusive bandage. The exposure period was 3 minutes, 1 hour or 4 hours. Residual test material was gently removed from the test sites with lukewarm water.
Skin reactions were recorded 30-60 minutes, 24, 48 and 72 hours after removal of the dressings, and at 7 and 14 days. Reactions were scored according to the scoring system set out in OECD 404. Rabbits were observed for mortality daily.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.22

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 3 minute exposure

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 3 minute exposure

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.56

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 1 hour exposure

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1 hour exposure

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: 4 hour exposure

Irritant / corrosive response data:

Very slight to moderate erythema and barely perceptible to slight oedema was observed following the 3-minute exposure, persisting for up to 7 days. 14 days after patch removal the skin showed very slight, barely perceptible erythema. The test site was observed to be dry, chapped and discoloured light brown. One animal had hardened skin 72 hours after patch removal, and 7 days after patch removal fine and rough desquamation partially occurred.
Moderate to severe erythema was observed up to 7 days after exposure for 1 hour. Barely perceptible to slight oedema was observed up to 24 hours after the 1 hour exposure. In addition, the skin was discoloured light brown, hardened and arched. Rough desquamation was observed from day 7 onwards. Eschar formation was observed in 2 animals after termination, and swelling of the treated skin was observed in one animal.
Following 4 hours exposure, the skin showed well defined to moderate erythema and very slight to moderate oedema up to 72 hours after patch removal. Very slight, barely perceptible erythema and oedema were observed 7 days after patch removal. The test sites were hardened, discoloured red-brown and the patch site framed white. The skin showed well defined to severe erythema 14 days after patch removal. One animal showed a defined oedema; oedema formation could not be observed in the other 2 animals due to hardening of the test site skin. The skin was roughly and finely desquamated, hardened, arched and discoloured red-brown. One animal was observed to have an open wound, and eschar formation was observed in all animals.

Other effects:

No other effects reported.

Any other information on results incl. tables

Table 1. Mean skin irritation scores after 3 minutes of exposure

If 3 animals or less	^*Mean score animal number			Maximum value	Maximum duration of any effect	Maximum value at the end of the observation period
	1	2	3
erythema/eschar	2.33	2	2.33	3	14 days	1
oedema	1.33	0	1.67	2	7 days	0
^*calculated on the basis of the scores at 24, 48, 72 hours for each animal

 

Table 2. Mean skin irritation scores after 1 hour of exposure

If 3 animals or less	^*Mean score animal number			Maximum value	Maximum duration of any effect	Maximum value at the end of the observation period
	1	2	3
erythema/eschar	4	4	2.67	4	7 days	0
oedema	0.67	0.33	0.67	2	1 day	0
^*calculated on the basis of the scores at 24, 48, 72 hours for each animal

 

Table 3. Mean skin irritation scores after 4 hours of exposure

If 3 animals or less	^*Mean score animal number			Maximum value	Maximum duration of any effect	Maximum value at the end of the observation period
	1	2	3
erythema/eschar	2	2	2	4	14 days	4
oedema	1.67	1.67	1.67	3	14 days	2
^*calculated on the basis of the scores at 24, 48, 72 hours for each animal

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

It was concluded that the test substance is corrosive to rabbit skin after 1 and 4 hours exposure.

Executive summary:

The acute skin irritant potential of Bardap 26 was investigated in nine New Zealand White rabbits. The rabbits were given a single topical application of 0.5 ml undiluted test substance/site under a semiocclusive dressing for either 3 minutes, 1 hour or 4 hours (3 rabbits per exposure period). The rabbits were observed for up to 14 days post-application.

Moderate skin irritation was observed after 3 minutes of exposure. The test substance was corrosive after 1 and 4 hours of exposure with necrosis, desquamation and scars observed at 14 days after both exposure periods. It was concluded that the test substance is corrosive to rabbit skin following 1 and 4 hours exposure, and should therefore be classified as Corrosive Category 1B according to Regulation (EC) No. 1272.