Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation/corrosion:

Not irritating. No significant concern can be reliably derived for the registration substance with respect to the endpoint skin irritation based on experimental data (OECD Guideline 439, OECD Guideline 404, GLP) . Weight of evidence built on several studies with closely related substances.

Eye irritation/corrosion:

Irreversible effects on the eye (OECD Guideline 405, GLP). The test substance was instilled into the conjunctival sac of the left eye of three young adult female Himalayian rabbits. The eyes were not washed. Evolvement of signs of serious eye damage from the 12th day after instillation. Corneal opacity and Iris effects did not subside until the 20th day after instillation (last examination). Read-across from Polyoxyethylene(5) lauryl ether carboxylic acid.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar / identical precursors under similar conditions
• they share structural similarities with common functional groups:
o fatty alcohol ethoxylates with a terminating carboxylic acid group
o a linear alkyl moiety (differing slightly in length and degree of saturation)
o ethylene oxide chain (varying slightly in mean length)

Therefore, read-across from the existing irritation and sensitisation studies on the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

Reason / purpose for cross-reference:
read-across source
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
test substance: mean of triplicates
Value:
87
Negative controls validity:
valid
Remarks:
set to 100%
Positive controls validity:
valid
Remarks:
27% of control
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: no
- Colour interference with MTT: no
ACCEPTANCE OF RESULTS:
The relative mean tissue viability obtained after 15 minutes treatment with the testsubstance compared to
the negative control tissues was 87%.
Since the mean relative tissue viability for the testsubstance was above 50% the testsubstance is consi
dered to be non-irritant.
The positive control had a mean cell viability after 15 minutes exposure of 27%.
The absolute mean OD570 of the negative control tissues was within the laboratory historical control data
range.
The standard deviation value of the percentage viability of three tissues treated identically was 6 to 15%,
indicating that the test system functioned properly.
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes
- Range of historical values if different from the ones specified in the test guideline:
-negative control range (OD): 0.576 - 1.994 (mean 0.91 ± 0.17; n=171)
-positive control range (OD): 0.020 - 0.408 (mean 0.10 ± 0.07; n=170)
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the available data Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is not be classified as irritating to the skin according to regulation (EC) 1272/2008.
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar / identical precursors under similar conditions
• they share structural similarities with common functional groups:
o fatty alcohol ethoxylates with a terminating carboxylic acid group
o a linear alkyl moiety (differing slightly in length and degree of saturation)
o ethylene oxide chain (varying slightly in mean length)

Therefore, read-across from the existing irritation and sensitisation studies on the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
other:
Basis:
animal: all animals
Time point:
24/48/72 h
Reversibility:
fully reversible within: observation priod
Remarks on result:
no indication of irritation

Skin Reaction

Reading (Hours)

Individual Scores - Rabbit Number and Sex

 

 

 

Polyoxyethylene(2.7) lauryl and miristyl ether carboxylic Sodium Salt (93%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

0.0

0.0

0.0

Oedema Formation

24/48/72 h

0.0

0.0

0.0

 

Polyoxyethylene(9) oleyl ether carboxylic acid (91%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

1.7

2.0

2.0

Oedema Formation

24/48/72 h

0.7

2.0

2.0

 

Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic Sodium salt (90%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

2.0

2.0

2.0

Oedema Formation

24/48/72 h

1.7

1.7

1.7

 

Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

1.0

1.0

1.0

Oedema Formation

24/48/72 h

0.0

0.0

0.0

 

 

All treated skin sites appeared normal at the end of the observation period.

 

All test substances were notirritating to rabbit skin according to the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the available data Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is not be classified as irritating to the skin according to regulation (EC) 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar / identical precursors under similar conditions
• they share structural similarities with common functional groups:
o fatty alcohol ethoxylates with a terminating carboxylic acid group
o a linear alkyl moiety (differing slightly in length and degree of saturation)
o ethylene oxide chain (varying slightly in mean length)

Therefore, read-across from the existing irritation and sensitisation studies on the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 20 d
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 13 d
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 11 d
Remarks on result:
positive indication of irritation

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

 

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0*/0*/0*

 0/0/0

2/2/2 

0#/1#/1# 

24 h

1/1/1 

1/1/1 

2/2/2 

2#/1#/1# 

48 h

1/1/1 

1/1/1 

2/2/2 

2#/1#/1# 

72 h

1/1/1 

1/1/1 

2/2/2 

2#/1#/1# 

Average 24h, 48h, 72h

1.0/1.0/1.0

1.0/1.0/1.0

2.0/2.0/2.0

2.0/1.0/1.0

4 d

1/1/1

2/1/2

2/2/2

2#/2#/1# 

5d

2/1/1

2/1/1

2/2/2

2#/2#/1# 

6d

2/1/1

2/1/1

2/2/2

2#/2#/1# 

7d (LH)

2/1/2

2/1/1

2/2/2

2/2/1

8d (LH)

1/1/2

2/1/1

1/2/1

2/2/1

9d (LH)

1/1/2

2/1/1

1/2/1

2/1/1

10d (LH)

1/1/2

2/1/1

1/1/1

2/1/1

11d (LH)

1/1/2

2/1/1

1/1/1

1/0/0

12d (LH)

1/1##/2##

2/1/1

1/1/1

1/0/0

13d

1/1/2###

1/1/1

1/1/1

0/0/0

14d

1/1/2###

1/1/2

1/1/1

0/0/0

15d

1/1/2###

1/1/2

1/1/1

0/0/0

16d

1/1/2###

1/1/2

1/1/1

0/0/0

17d

1/1/2###

1/1/2

1/0/1

0/0/0

18d

1/1/2###

1/1/2

1/0/1

0/0/0

19d

1/1/2###

1/1/2

1/0/1

0/0/0

20d

1**/1/2

1/1/2

1/0/1

0/0/0

Reversibility*)

 n

 n

 n

 c

Average time (unit) for reversion

 

 

 

 14 d

24 hrs, 7 d and 14 d fluorescein tests: confirmed the corneal changes

* transparent substance deposits on the cornea ** detachment of the cornea

# whitish conjunctivalhypersecretion (grades 1 - 3) (LH) loss of hair around the eyelids

## pericorneal vascular injection ### pericorneal vascular injection, commencing detachment of the cornea

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

 

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the available data Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid has to be classified as irreversible effects to the eye (Category 1) and labelled with H318 (Causes serious eye damage) according to regulation (EC) 1272/2008.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data on skin and eye irritation are not available for the target substance Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid. For the assessment of local effects ofPolyoxyethylene(1 to 2.5) oleyl ether carboxylic acidresults from the following studies are taken into consideration:

-      An in vivo OECD 405 acute eye irritation / corrosion study with the source substance Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90%)

-      An in vitro skin irritation study according to OECD 439 with the source substance Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (82%)

-      several OECD 404 primary dermal irritation studies in vivo with the source substances:

o   Polyoxyethylene(9) oleyl ether carboxylic acid (91%)

o   Polyoxyethylene(4.5) lauryl ether carboxylic Sodium salt (90%)

o   Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90%)

o   Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt

A justification for read-across is given below.

 

Skin Irritation

In a dermal irritation study performed in accordance with OECD Guideline 439 (In Vitro Skin Irritation) (26 July 2013) and EU method B.46 (In vitro skin irritation: reconstructed human epidermis model test) (20 July 2012), the test substance Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid (82%) was applied to the three-dimensional human epidermis model tissue (EPISKIN Small Model (EPISKIN-SM, 0.38 cm², Batch no.: 14-EKIN-001) for an exposure period of 15 minutes. The number of replicate tissues was three.

The test substance was applied undiluted in an amount of 25 µl directly on top of the skin tissue. After 15 minutes exposure at room temperature, the tissues were washed with phosphate buffered saline. Subsequently the tissue constructs were incubated for 42 h at 37°C. Cytotoxicity (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

The positive (5% SDS) and negative (PBS) control gave responses that were within the acceptancecriteria and as such demonstrated the validity of the study.

The relative mean tissue viability obtained after 15 minutes treatment with Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid compared to the negative control tissues was 87%. Since the mean relative tissue viability for the test substance was above 50%, Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid (82% a.i.) is identified to be not irritating.

Primary dermal irritation studies according to OECD Guideline 404, adopted 17 July 1992, and EU Method B.4 were conducted with four different closely related read-across substances (Polyoxyethylene(9) oleyl ether carboxylic acid (91%), Polyoxyethylene(4.5) lauryl ether carboxylic Sodium salt (90%), Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90%) andPolyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt)

In all four studies young adult rabbits of one sex were dermally exposed to 0.5 mL of the respective testsubstance to 6 cm² skin surface. The animals were subsequently exposed for 4 hours. Animals then were observed for either 72 hours, 7 days or 14 days.

 

In none of the studies, the respective test substance had to be classified based on the individual mean scores.

 

Skin Reaction

Reading (Hours)

Individual Scores - Rabbit Number and Sex

Polyoxyethylene(9) oleyl ether carboxylic acid (91%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

1.7

2.0

2.0

Oedema Formation

24/48/72 h

0.7

2.0

2.0

 

Polyoxyethylene(4.5) lauryl ether carboxylic Sodium salt (90%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

2.0

2.0

2.0

Oedema Formation

24/48/72 h

1.7

1.7

1.7

 

Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90%)

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

1.0

1.0

1.0

Oedema Formation

24/48/72 h

0.0

0.0

0.0

 

Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt

Animal #1

Animal #2

Animal #3

Erythema/Eschar Formation

24/48/72 h

0.0

0.0

0.0

Oedema Formation

24/48/72 h

0.0

0.0

0.0

 

 

All treated skin sites appeared normal at the end of the observation period.

 

All test substances were not irritating to rabbit skin according to the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

 

 

Eye Irritation 

In a primary eye irritation study according to OECD guideline 405 (February 24, 1987) 0.1 mL of Polyoxyethylene(4.5) lauryl andmiristylether carboxylic acid (90% a.i.) was instilled into the conjunctival sac of one eye of 3 young adult Himalayan rabbits not followed by washing. The untreated eyes served as controls. Animals were then observed for 20 days. Irritation was scored by the method of Draize.

Corneal opacity (grade 1 and 2) which was observed in all three rabbits between 24 hours and 20 days after instillation (last examination time-point). From the 12th day after instillation a pericorneal vascular injection was observed for two rabbits, in one of them a commencing detachment of the cornea occurred from the next day onwards. Corneal changes were confirmed by three fluorescein tests (24 hours, 7 and 14 days after dosing). Opacity covered up to the whole area. Corneal opacity did not subside until the 20th day after instillation (last examination).

At the examinations 24 hours to 20 days after instillation, the iris of all animals was affected with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection (any of these or combination of any thereof), the iris was still reacting to light (grade 1) or showed no reaction to light, had haemorrhages and/or gross destruction (any or all of these, grade 2).

Conjunctival redness (grade 1 and 2) was seen during the examinations 1 hour to 16 days after instillation in all rabbits, in two animals the redness was observed until the 20th day after instillation. Conjunctival chemosis (grade 1 and predominantly grade 2) was evident in all rabbits between 24 hours and 10 days after instillation, in one rabbit until the 12th day after instillation.

Conjunctival hypersecretion (grade 1 to 3) was observed in all three rabbits during the examinations 1 hour to 6 days instillation. Conjunctival chemosis had disappeared 13 days after instillation, conjunctival redness had not disappeared until 20 days after instillation (last examination).

Thus, Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90% a.i.), produced irreversible effects to the eye in this study and thus has to be classified as Category 1 (irreversible effects on the eye).

 

Respiratory irritation

No data on the respiratory irritation of Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid are available.

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

 

Justification for read-across

Hypothesis for the analogue approach

This read-across is based on the hypothesis that source and target substances have similar toxicological properties because

·        they are manufactured from similar / identical precursors under similar conditions

·        they share structuralsimilarities with common functional groups:

o   fatty alcohol ethoxylates with a terminating carboxylic acid group

o   a linear alkyl moiety (differing slightly in length and degree of saturation)

o   ethylene oxide chain (varying slightly in mean length)

Therefore, read-across from the existing irritation studies on the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

The justification of the proposed read-across approach is elaborated in the next chapters.

 

1. Substance Identities

The target and source substances are manufactured by the reaction of fatty alcohol ethoxylates with sodium chloroacetate under alkaline conditions. The main components can be described as fatty alcohol ethoxylate linked via ether bond to the acetic acid.The general structure of the alkyl polyglycol ether carboxylic acidis:

 

 R-O-(CH2CH2O-)nCH2COOH

 

with R = linear alkyl chain, C12 – C18, C18:1

and n = 1 - 9

 

The target substance Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid contains mainly 9-octadecenyl chains (=C18 unsaturated) and a mean number of 2.5 EO units.

 

The source substances vary in thecarbon chain length of the alkyl chain as well as in the number of EO units:

 

The source substance Polyoxyethylene(9) oleyl ether carboxylic acid contains a9-octadecenyl chain (=C18 unsaturated) and a mean number of 9 EO units.

The source substance Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid contains lauryl and myristyl chains (C12, C14, saturated) and a mean number of 4.5 EO units.

 

The source substance Sodium polyoxyethylene(4.5) lauryl ether carboxylate contains lauryl chains (C12, saturated) and a mean number of 4.5 EO units.

 

The source substance Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt contains a lauryl chain (C12, saturated) and a mean number of 2.5 EO units.

 


Table 1: Substance identities

 

Target substance

Sourcesubstances

 

 

 

Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid

Polyoxyethylene(9) oleyl ether carboxylic acid

Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid

Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt

Sodium polyoxyethylene(4.5) lauryl ether carboxylate

CAS number

57635-48-0

57635-48-0

27306-90-7

33939-64-9

33939-64-9

Moles EO (mean)

2.5

9

4.5

2.5

4.5

Chain length distribution

C12: < 5%

C14: < 10%

C16: 2 - 25%

C18 1 - 15 %

C18:1(oleyl):60- 95%

C12: < 5%

C14: < 10%

C16: 2 - 25%

C18 1 - 15 %

C18:1(oleyl):60- 95%

C12: 70%

C14: 30%

C12 90-100%

C12: 90-100%

Composition

Alkylethercarboxylic acid: 60-90%

 

Alkylethoxylate < 2.5 EO: 5-30%

 

Ester: 0-25%

n.a.

Fatty alcohol: 8%

n.a.

Dodecanol, ethoxylated: 2%

 

 

Minor constituents

Alkylethercarboxylic acid: 30-80%

 

Alkylethoxylate <2.5EO: 5-40%

 

Esterification products ofAlkylethercarboxylic acidand Alkylethoxylate: 1-35%

 

Fatty alcohol: < 1%

Alkylethercarboxylic acid: 30-80%

 

Alkylethoxylate:0-40%

 

Esterification products of Alkylethercarboxylic acid and Alkylethoxylate: 1-35%

 

Fatty alcohol: < 1%

Alkylethercarboxylic acid: 30-80%

 

Alkylethoxylate: 0-40%

 

Esterification products of Alkylethercarboxylic acid and Alkylethoxylate: 1-35%

 

Fatty alcohol: < 10 %

Alkylethercarboxylic acid: 30-80%

 

Alkylethoxylate: 0-40%

 

Esterification products of Alkylethercarboxylic acid and Alkylethoxylate: 1-35%

 

Fatty alcohol: < 1%

Alkylethercarboxylic acid: 30-80%

 

Alkylethoxylate: 0-40%

 

Esterification products of Alkylethercarboxylic acid and Alkylethoxylate: 1-35%

 

Fatty alcohol: < 1%


2. Impurities

The target and source substances belong to the group of alkyl polyglycol ether carboxylic acid, which are manufactured from different fatty alcohol ethoxylates as raw material. Since the impurities in the fatty alcohol ethoxylates are considered to be comparable, the impurities of the registration substance and of other alkyl polyglycol ether carboxylic acid are expected to be comparable. A difference in irritation potential due to different impurity profiles is not likely.

 

3. Analogue approach justification

The read-across hypothesis is based on structural similarity of target and source substances. The respective reliable data (RL 1 or 2) are summarized in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.

 

The read-across from the source substances is justified:

 

a)    Based on the information given in section 1, it can be concluded that the substances are similar in structure, since they are manufactured from similar or identical precursors under similar conditions and all contain the same functional groups. Thus a common mode of action can be assumed.

b)   The content of minor constituents in all products are comparable and differ to an irrelevant amount.

c)    The only deviations within this group of substances is a variety in their alkyl chain length as well as in the number of EO units, which is not expected to have a relevant impact on intrinsic toxic activity.

 

3.1. Structural similarity and functional groups (Table 1)

The general structure of the alkyl polyglycol ether carboxylic acidis:

 

 R-O-(CH2CH2O-)nCH2COOH

 

with R = linear alkyl chain, C12 – C18, C18:1

and n = 1 - 9

 

target substance:

Polyoxyethylene(2.5) oleyl ether carboxylic acid: R = C18:1, n =2.5.

 

source substances:

Polyoxyethylene(9) oleyl ether carboxylic acid: R = C18:1, n =9

Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid: R = C12-14, n =4.5

 

Sodium polyoxyethylene(4.5) lauryl ether carboxylate: R = C12, n =4.5

 

Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt: R = C12, n =2.5

 

 

3.2. Differences

 

Differences in chemical and other intrinsic properties of the target and source substances potentially arise from the following facts:

-      Differences in C-chain length and unsaturated moieties:

The source substances Sodium polyoxyethylene(4.5) lauryl ether carboxylate, Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid, as well as Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Saltcontain mainly shorter chain lengths (C12 - 14, saturated) compared to the target substance (mainly C18:1).

The presence of unsaturated C18 chains may be considered as a worst case with respect with respect to local effects (irritation, sensitisation) (HERA, 2002; Stillman, 1975; Aungst, 1989). As also data on skin irritation and sensitisation are available for the source substance Polyoxyethylene(9) oleyl ether carboxylic acid (containing C18:1 chains like the target substance), it is demonstrated based on experimental data, that the small difference in C-chain length and degree of unsaturation is not relevant for this read-across approach.

 

-      Differences in number of EO units:

The degree of ethoxylation may influence the irritation potential: longer EO chains may exhibit a slightly lower irritation potential (HERA, 2009). However, the difference in number of EO units is rather small between the target and source substances (ranging from 2.5 to 9). Moreover, data on skin irritation are available for the source substance Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt (with a number of EO units comparable to the target substance). It is demonstrated based on experimental data, that the small difference in the number of EO units is not relevant for this read-across approach.

 

-      Na Salt vs. Carboxylic acid

The target substance Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid and the source substances Polyoxyethylene(9) oleyl ether carboxylic acid and Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid are carboxylic acids, whereas the source substances Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt and Sodium polyoxyethylene(4.5) lauryl ether carboxylate are Sodium salts of carboxylic acids. Based on the results obtained with Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid and Sodium polyoxyethylene(4.5) lauryl ether carboxylate, which were both only slightly irritating to skin, it is demonstrated that this difference has no relevant effect on the skin irritation potential.

 

The target and source substances belong to the group of alkyl polyglycol ether carboxylic acid, the structural difference being only different alkyl moieties and number of ethylene glycol units. Based on the incremental change in the chemical structures among the members, the read-across is justified with high confidence.

 

4. Data matrix

 

Polyoxyethylene(2.5) oleyl ether carboxylic acid

Source chemicals: Alkyl polyglycol ether carboxylic acid

Endpoints

 

Hazard profile/ Hazard assessment method

Hazard profile

 

Irritation

Skin

read-across

Not irritating

C12-14/4.5EO/27306-90-7

 

C12-14/2.5EO/NA Salt/33939-64-9

 

Oleyl/9EO/57635-48-0

 

C12-14/4.5EO Na Salt/33939-64-9

Eye

read-across

Irreversible effects on the eye

C12-14/4.5EO/27306-90-7

Skin Sensitization

 

read-across

not sensitizing

Oleyl/9EO/57635-48-0

 

C12-14/4.5EO/27306-90-7

 

 

Schematic overview skin irritation

 

 

Target substance

 

 

 

 

Polyoxyethylene(9) oleyl ether carboxylic acid

Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid

Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt

Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid

Sodium polyoxyethylene(4.5) lauryl ether carboxylate

Moles EO (mean)

9

2.5

2.5

4.5

4.5

Main alkyl chain

C18:1

C18:1

 

C12

C12 / C14

C12

Na salt / free acid

Acid

Acid

Na salt

Acid

Na salt

 

Schematic overview eye irritation

 

Target substance

 

 

Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid

Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid

Moles EO (mean)

2.5

4.5

Main alkyl chain

C18:1

 

C12 / C14

Na salt / free acid

Acid

Acid

 

Based on interpolation from the results obtained with the source substances Polyoxyethylene(9) oleyl ether carboxylic acid, Polyoxyethylene(2.5) lauryl ether carboxylic Sodium Salt, Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid, and Sodium polyoxyethylene(4.5) lauryl ether carboxylate, which were not irritating to skin, the target substance Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is considered to be not irritating to skin

Based on the results obtained with the source substance Polyoxyethylene(4.5) lauryl miristyl ether carboxylic acid, the target substance Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is considered to cause irreversible effects to the eye.

 

5. Quality of the experimental data of the analogues

The available data are adequate and sufficiently reliable to justify the read-across approach.

The studies were conducted according to OECD Guideline 404 or 405 and are reliable or reliable with restrictions (RL1-2).

The test materials used in the respective studies represent the source substance as described in the hypothesis in terms of substance identity and minor constituents.

Overall, the study results are adequate for the purpose of classification and labelling and risk assessment

 

6. References

Aungst, 1989. Structure/Effect Studies of Fatty Acid Isomers as Skin Penetration Enhancers and Skin Irritants. Pharmaceutical Research, March 1989, Volume 6, Issue 3, pp 244-247

 

HERA, 2002: Fatty Acid Salts – Human Health Risk Assessment; http://www.heraproject.com/files/5-HH-04-HERA%20Fatty%20acid%20salts%20HH%20web%20wd.pdf

 

HERA, 2009: Alcohol Ethoxylates; http://www.heraproject.com/files/34-F-09%20HERA%20AE%20Report%20Version%202%20-%203%20Sept%2009.pdf

 

Stillman et al., 1975. Relative irritancy of free fatty acids of different chain length. Contact Dermatitis. 1975;1(2):65-9.

 

 

 

Conclusion

Human data on local irritation/corrosion are not available for the target substance Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid but reliable and relevantin vitro and in vivo data regarding skin irritation show only mild to moderate irritating properties (conclusive but not sufficient for classification).

 

All source substances do not have to be classified as irritating to skin in vitro and in vivo.The structural similarities between the source and the target substances and the similarities in their breakdown products as presented above justify the read-across hypothesis. Adequate and reliable scientific information indicates that the source and target substances and their subsequent degradation products have similar toxicity profiles under the experimental conditions in the considered studies for the endpoint skin irritation. Testing of skin irritation of Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is therefore scientifically not justified and the results of the source substances are used to fulfill this information requirement.

 

Polyoxyethylene(4.5) lauryl and miristyl ether carboxylic acid (90% a.i.) is classified for irreversible effects on the eye (Category 1) in a reliable and relevant study. Because of the high structurally similarity to the target substance, Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is also classified for irreversible effects on the eye (Category 1) and there is therefore no need to conduct a study on the target substance itself (Reach regulation, Annex VIII, 8.2.1, Column 2).

Justification for classification or non-classification

Based on the available data, Polyoxyethylene(1 to 2.5) oleyl ether carboxylic acid is not be classified as irritating to the skin but as irreversible effects to the eye (Category 1) and labelled with H318 (Causes serious eye damage) according to regulation (EC) 1272/2008.