Registration Dossier

Administrative data

Description of key information

There is no skin irritation/corrosion data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs , but there are two studies for the read across substance Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 registered under 2,2’-(C16 -18 (evennumbered, C18 unsaturated) alkyl imino) diethanol CAS 1218787-32-6,.  Available for skin corrosion/irritation a validity 1 GLP study to OECD 404 except that weanling domestic pigs were used and a validity 2 GLP OECD 404 study in rabbits that show corrosion after a 4 hour exposure OECD/GHS Category 1C.  There are no data on eye irritation, but this not a concern as the corrosive classification for the skin will also be applied to the eyes via the hazard statement.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
September 1989 - January 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Substance: CESIO 33. No data on batch no. and composition. Basic data given according to guidelines/standards.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
6 animals rather than 3 animals were used
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 13-21
- Humidity (%): 47-69
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 26 September 1989 To: 4 January 1990 (for all 17 compounds)
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours (Exposure of 3 min was also preformed but no data reported).
Observation period:
up to 14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm gauze patch
- % coverage: not indicated
- Type of wrap if used: gauze patch was secured with surgical adhesive tape (2.5 x 4 cm); the trunk was wrapped in an
elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, by gently swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: immediately following patch removal


SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by
definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
2.67
Max. score:
3
Reversibility:
not reversible
Remarks:
within 14 days
Remarks on result:
other: scar tissue in 5/6 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks:
within 14 days
Remarks on result:
other: evaluation in 5/6 animals at day 7/14 not possible due to presence of other adverse dermal reactions
Irritant / corrosive response data:
Severe dermal responses were produced. The adverse skin reactions sometimes precluded accurate evaluation of erythema and
oedema. Very slight to well -defined erythema, haemorrhage of the dermal capillaries and slight to moderate oedema were noted
one hour after patch removal. The responses increased in severity and at subsequent observations were identified as well -
defined and moderate to severe oedema, haemorrhage of the dermal capillaries, blanching of the skin, a brown discolouration of theepidermis, scabbing, loss of skin flexibility, a straw-coloured crust (possible hyperkeratinisation), desquamation, thickening of the
skin, reduced re-growth of fur and glossy skin. Scar tissue, indicative of dermal corrosion was noted in five out of six rabbits.
Other effects:
No data.

Summary of dermal irritation (following 4-h application)

Animal no.

Effect

Hour

Days after application

Mean score erythema

(24/48/72 h)

Mean score oedema

(24/48/72 h)

1

1

2

3

7

14

25 M

Erythema

Oedema

2

2

3

4

2

4

?

?

?

?

?

?

2.5?

4?

28 F

Erythema

Oedema

2

2

3

4

3

3

?

?

?

?

0

?

3?

3.5?

31 M

Erythema

Oedema

2

3

3

4

3

4

3

3

?

?

?

?

3

3.67

33 M

Erythema

Oedema

2

2

3

4

3

4

3

3

?

?

?

?

3

3.67

73 M

Erythema

Oedema

2

2

2

4

2

4

2

3

?

?

?

0

2

3.67

134 F

Erythema

Oedema

1

2

2

4

3

3

?

?

?

?

?

?

2.5?

3.5?

Mean all animals

2.67?

3.67?

? Unable to evaluate degree of erythema or oedema due to presence of other adverse dermal reactions

At day 7: scabs, dry straw-coloured crust, sometimes flaking from the skin (possible hyperkeratinisation)

At day 14: desquamation, thickening of the skin, scabs, scar tissue, reduced re-growth of fur, skin glossy in appearance (keratinolysis)

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test material was considered to be corrosive (Category 1C) to the rabbit skin according to OECD-GHS. This was essentially
based on the formation of scar tissue, indicative of dermal corrosion, in 5 out of 6 rabbits.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irri tation/Corrosion" and Method B4 of the EC. A single

4 -hour, semi-occluded application of the test material to the intact skin of six rabbits produced severe dermal responses. Scar tissue, indicative of dermal corrosion was noted in 5 out of 6 rabbits 14 days after application. The test material was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the substance is classified as irritating to eyes with risk of serious damage to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no skin irritation/corrosion data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs , but there are two studies for the read across substance Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 registered under 2,2’-(C16 -18 (evennumbered,C18 unsaturated) alkyl imino) diethanol CAS 1218787-32-6,. Available for skin corrosion/irritation is a validity 1 GLP study to OECD 404 in 2002, however rather than use of rabbits the study was carried out using weanling domestic pigs.  No mortality or clinical signs of toxicity were observed during the 168-hour observation period.

Scab formation was observed on all three animals beginning at the 48 hour observation period and extending to the 168 hour observation period (slight/moderate scabbing). Exfoliation (slight/moderate) was observed on two of the three animals beginning at the 120 hour observation period extending to the 168 hour observation period.

Based on this study Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 can be classified as a mild irritant to the skin (Category 3 according to OECD-GHS.

 

The second study that is available is a CESIO validity 2 study but done to GLP following OECD guideline 404 The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" and Method B4 of the EC. A single 4 -hour, semi-occluded application of the test material to the intact skin of six rabbits produced severe dermal responses. Scar tissue, indicative of dermal corrosion was noted in 5 out of 6 rabbits 14 days after application.

 

As the rabbit is the routine species for this test method, the results in the rabbit have been used for the classification, as the use of the weanling pig in the study has not been fully validated. The Ethanol, 2,2’-iminobis-, N-tallow alkyl derives was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria. This classification will be read across to Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs

 

There are no data on eye irritation, but this not a concern as the corrosive classification for the skin will also be applied to the eyes via the hazard statement.

Justification for selection of skin irritation / corrosion endpoint:

This is a rabbit study, the prefered model for classification and labelling, other data from the pig is not fully validated.

Justification for selection of eye irritation endpoint:

Read across form an appropraite substnace.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

The CESIO study while validity 2 was used as the basis for classification as it uses the OECD guideline recommended species of the rabbit and therefore the results are comparable with other testing done for classification purposes. After a 4 hour application scar tissue, indicative of dermal corrosion was noted in 5 out of 6 rabbits 14 days after application. The Ethanol, 2,2’-iminobis-, N-tallow alkyl derives was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria.

 

There are no studies on eye irritation with Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 but due to the corrosive nature to the skin of the substance it is not ethical to carry out this animal study. The corrosive classification of the Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives and the required risk management methods to avoid eye contact, so the lack of an eye irritation study will not affect the safe handling of the substance. Ethanol, 2, 2’-iminobis-, N-tallow alkyl derives will be considered to be corrosive to eyes based on the effects on the skin as the GHS/CLP phases for skin irritation also includes serious eye damage.