Propanol, iminobis-, N-(C16-18 and C18-unsatd. alkyl) derivs.

Endpoint summary

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-C12-18-alkyl derives CAS No 61791-31-9 registered under 2,2’-(C12-18 evennumbered alkyl imino) diethanol CAS 71786-60-2,.  Available for skin corrosion/irritation a validity 1 GLP study to OECD 404 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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

The study was performed between 15 April 2010 and 29 April 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Justification for type of information:

See section 13.2 for the read-across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

One New Zealand White rabbit was supplied by Harlan Laboratories U.K. Ltd., Loughborough, UK. At the start of the study the animal weighed 2.79 kg and was twelve to twenty weeks old. After an acclimatisation period of at least five days the animal was given a number unique within the study which was written with a black indelible marker pen on the inner surface of the ear and on the cage label.

The animal was housed in a suspended cage. Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, axon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animal was provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
0.5 ml

- Concentration (if solution):
Not applicable.

VEHICLE
Not applicable.

- Concentration (if solution):
Not applicable.

- Lot/batch no. (if required):
Not given in study report.

Duration of treatment / exposure:

3-Minutes, 1-Hour and 4-Hours

Observation period:

14 days

Number of animals:

1

Details on study design:

TEST SITE
- Area of exposure:
On the day of the test three suitable sites were selected on the back of the rabbit

- % coverage:
Not given in study report.

- Type of wrap if used:
Test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
Any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.

- Time after start of exposure:
3 minutes, 1 hour and 4 hours.


SCORING SYSTEM:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary
irritation and scored according to the following scale (table below).
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 4

Max. score:

4

Reversibility:

not reversible

Remarks:

Corrosive effects noted

Remarks on result:

other: Max score not really applicable due to corrosive effects

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

> 4

Reversibility:

not reversible

Remarks:

Irreversible effetcs noted

Remarks on result:

other: Evaluation of oedema not possible due to adverse dermal reactions

Irritant / corrosive response data:

The individual scores for erythema/eschar and oedema are given in remarks on results including tables and figures.
3-Minute Exposure Period

The scores for erythema/eschar and oedema are given in Table 1.
Very slight erythema was noted at the treated skin site at the 24, 48 and 72 Hour observations.
The treated skin site appeared normal at the 7-Day observation.

1-Hour Exposure Period

The scores for erythema/eschar and oedema are given in Table 1.
Very slight erythema was noted at the treated skin site immediately and one hour after patch removal with well-defined erythema and slight oedema
noted at the 24, 48 and 72 Hour observations. The erythema extended approximately 2 cm beyond the test site at the 24, 48 and 72 Hour
observations. Very slight erythema, very slight oedema and severe desquamation were noted at the treated skin site at the 7 Day observation. Slight desquamation was noted at the treated skin site at the 14 Day observation.

4-Hour Exposure Period

The scores for erythema/eschar and oedema are given in Table 2.
Moderate to severe erythema and slight oedema were noted at the treated skin site immediately and one hour after patch removal. A hardened, dark
brown/black coloured scab, preventing accurate evaluation of erythema and oedema, was noted at the treated skin site at the 24, 48 and 72 Hour and 7 Day observations. Well-defined erythema surrounding the scab was noted at the 24, 48 and 72 Hour observations. Thickening of the skin was
noted at the treated skin site at the 14-Day observation.

The individual scores for erythema/eschar and oedema are given in the folowing table.

Table1              Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction	Observation Time (following patch removal)	Individual Scores - Rabbit Number and Sex
		69076
		3-Minute Exposure	1-Hour Exposure
Erythema/Eschar Formation	Immediately	0	1
	1 Hour	0	1
	24 Hours	1	2R
	48 Hours	1	2R
	72 Hours	1	2R
	7 Days	0	1D
	14 Days	0	0D*
Oedema Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	2
	48 Hours	0	2
	72 Hours	0	2
	7 Days	0	1
	14 Days	0	0

R=      Erythema extends approximately 2 cm beyond the test site

D =      Severe desquamation

D* =     Slight desquamation

Table2          Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Scores – Rabbit Number and Sex
		69076Male
Erythema/Eschar Formation	Immediately	3
	1 Hour	3
	24 Hours	?eStWe
	48 Hours	?eStWe
	72 Hours	?eStWe
	7 Days	?eSt
	14 Days	0Th
Oedema Formation	Immediately	2
	1 Hour	2
	24 Hours	?od
	48 Hours	?od
	72 Hours	?od
	7 Days	?od
	14 Days	0

St=    Hardened dark brown/black coloured scab

Th =    Thickening of the skin

We =  Well-defined erythema surrounding other skin reactions

?e =    Adverse skin reactions prevent accurate evaluation of erythema

?od =  Adverse skin reactions prevent accurate evaluation of oedema

The test material was classified as CORROSIVE to rabbit skin.

The test material was also classified as corrosive to rabbit skin according to EU labelling regulations Commission Directive 2001/59/EC. The symbol “C”, the indication of danger “Corrosive” and the risk phrase R 34 “CAUSES BURNS” are therefore required.

Iirreversible alteration of the dermal tissue noted. Test material is classified as corrosive to rabbit skin. Classification according to Draize, therefore, not be applicable.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The test material was classified as CORROSIVE to rabbit skin.

The test material was also classified as corrosive to rabbit skin according to EU labelling regulations Commission Directive 2001/59/EC. The symbol “C”, the indication of danger “Corrosive” and the risk phrase R 34 “CAUSES BURNS” are therefore required.

Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

§        Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

Results. 

3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

A single 4-hour, semi-occluded application of the test material to the intact skin of one rabbit produced moderate to severe erythema, slight oedema and a hardened, dark brown/black coloured scab which prevented accurate evaluation of erythema and oedema. Well-defined erythema surrounding the scab was also noted. Thickening of the skin was noted at the 14-Day observation.

Conclusion. 

The test material was classified as CORROSIVE to rabbit skin.

The test material was also classified as corrosive to rabbit skin according to EU labelling regulations Commission Directive 2001/59/EC. The symbol “C”, the indication of danger “Corrosive” and the risk phrase R 34 “CAUSES BURNS” are therefore required.

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 does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

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-C12-18-alkyl derives CAS No 61791-31-9 registered under 2,2’-(C12-18 evennumbered alkyl imino) diethanol CAS 71786-60-2,.  Available for skin corrosion/irritation a validity 1 GLP study to OECD 404 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.

 

In the primary study on Ethanol, 2,2’-iminobis-, N-C12-18-alkyl derives CAS No 61791-31-9 performed in 2010, the 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects. A single 4-hour, semi-occluded application of the test material to the intact skin of one rabbit produced moderate to severe erythema, slight oedema and a hardened, dark brown/black coloured scab which prevented accurate evaluation of erythema and oedema. Well-defined erythema surrounding the scab was also noted. Thickening of the skin was noted at the 14-Day observation. This resulted in a classification as Category 1C according to GHS.

 

The second study that is available is a validity 2 study but done to GLP following OECD guideline 404 The study was performed in 1985 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 three rabbits produced persistent moderate to severe irritation. Necrotic areas were observed in 2/3 animals 1 to 5 days after application. The test material was therefore classified as corrosive (Category 1C) according to OECD-GHS criteria.

 

Results for the circa 2010 OECD guideline 404 test have been used for classification. The use of more up-to-date guidelines likely increases the accuracy and reliability of the result. The 2,2’-(C12-18 evennumbered alkyl imino) diethanol was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria. This classification will be read across to di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine.

 

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

Results for the circa 2010 OECD guideline 404 test have been used for classification. The use of more up-to-date guidelines likely increases the accuracy and reliability of the result. The 2,2’-(C12-18 evennumbered alkyl imino) diethanol was therefore classified as corrosive (Category 1C) to the rabbit skin, according to OECD/GHS criteria. This classification will be read across to di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine.

 

There are no studies on eye irritation with di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine CAS No. 1309955-79-0 previously 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 2,2’-(C12-18 evennumbered alkyl imino) diethanol 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. di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine 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.