Registration Dossier

Administrative data

Description of key information

Relevant, reliable and adequate data on skin and eye irritation of AAPBs are available on spray dried samples of Coco AAPB and C8-18 AAPB, on aqueous solutions of Coco AAPB with concentrations from 35 % a. i. down to 3 % a. i.. In addition data from a skin irritation study (30 % a. i.) and an eye irritation study (29 % a. i.) with aqueous C8-18 AAPB are available. 
As spray dried powder as well as in the technically relevant aqueous concentrations of up to 35 % a. i., AAPB caused only slight transient irritation at the rabbit skin in studies performed according to EU Method B.4 and/or OECD TG 404. In eye irritation studies, aqueous solutions down to concentrations of 25 % a. i. and the spray dried AAPB powder induced corneal and/or iris damage in rabbits which was still present in some animals at the end of the observation period of 21 days. 5 to 10 % solutions caused mild to moderate effects, which were all reversible within the observation period. AAPB concentrations ≤ 4.5 % caused only minimal transient eye effects with mean scores following grading at 24, 48 and 72 hours after instillation well below the values triggering a classification.
The obtained results from Coco AAPB and C8-18 AAPB are considered to be valid for the whole group of AAPBs.

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
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
see "General Justification for Read-Across" attached to IUCLID section 13

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Mutual read across from the AAPBs to one another is justified:

a) Based on the information given in section 1, it can be concluded that all AAPBs mentioned above are similar in structure, since they are manufactured from similar resp. 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 deviation within this group of substances is a minor variety in their fatty acid moiety, which is not expected to have a relevant impact on intrinsic toxic or ecotoxic activity and environmental fate. Potential minor impact on specific endpoints will be discussed in the specific endpoint sections.

The read-across hypothesis is based on structural similarity of target and source substances. Based on the available experimental data, including key physico-chemical properties and data from toxicokinetic, acute toxicity, irritation, sensitisation, genotoxicity and repeated dose toxicity studies, the read-across strategy is supported by a quite similar toxicological profile of all five substances.
The respective data are summarised in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see "General Justification for Read-Across" attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see "General Justification for Read-Across" attached to IUCLID section 13

4. DATA MATRIX
see "General Justification for Read-Across" attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1.67
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - 1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
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
see "General Justification for Read-Across" attached to IUCLID section 13

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Mutual read across from the AAPBs to one another is justified:

a) Based on the information given in section 1, it can be concluded that all AAPBs mentioned above are similar in structure, since they are manufactured from similar resp. 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 deviation within this group of substances is a minor variety in their fatty acid moiety, which is not expected to have a relevant impact on intrinsic toxic or ecotoxic activity and environmental fate. Potential minor impact on specific endpoints will be discussed in the specific endpoint sections.

The read-across hypothesis is based on structural similarity of target and source substances. Based on the available experimental data, including key physico-chemical properties and data from toxicokinetic, acute toxicity, irritation, sensitisation, genotoxicity and repeated dose toxicity studies, the read-across strategy is supported by a quite similar toxicological profile of all five substances.
The respective data are summarised in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see "General Justification for Read-Across" attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see "General Justification for Read-Across" attached to IUCLID section 13

4. DATA MATRIX
see "General Justification for Read-Across" attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Irritation parameter:
other: irreversible effects to the eye
Basis:
animal #1
Time point:
other: 1h
Reversibility:
other: animal was humanely killed because of severity of effects after the first scoring one hour after treatment
Remarks on result:
probability of severe irritation
Remarks:
extreme bleeding of conjunctivae and nictating membrane, blood coloured discharge, reddened iris, cornea opacity score 2 of one half of the cornea, iritis score 1, conjunctival erythema and chemosis score 3
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Studies on skin and eye irritation are available for spray dried samples of C8-18 AAPB as well as for the closely related source substance Coco AAPB (C8-18 and C18 unsatd. AAPB).

In addition, data from a skin irritation study (30 % a.i.) and an eye irritation study (29 % a.i.) of aqueous C8-18 AAPB are available.

A justification for read-across is given below.

 

Skin irritation/corrosion

In the key studies on primary dermal irritation, performed according to EU Method B.4 and/or OECD Guideline 404, rabbits were exposed to 0.5 g or 0.5 mL of test substance for 4 hours under semi-occlusive conditions, with one exception (35 % a.i. Coco AAPB) were an occlusive dressing was used. Irritation was scored according to the method of Draize.

In both studies with spray dried solids, test substance was moistened with physiological saline or water prior to application. In the study performed with Coco AAPB (99.4 % dry solids) very slight (score 1) to slight (score 2) edema were observed within the first 24 hours in 2/3 animals. Erythema were observed in all animals, up to score 3 in one animal. All skin effects were fully reversible within 72 hours. In the study performed with C8-18 AAPB dry solids (84 % a.i.) treated animals showed no skin reactions at all.

Even though Coco AAPB at the technical relevant concentration of 35 % a.i. was applied under more intensive occlusive conditions, only a very slight edema (score 1) in one animal and erythema scores of 1 or 2 in two animals were observed. Effects were fully reversible within 8 days. In a further study, C8-18 AAPB (30 % a. i) was applied under a semi-occlusive dressing. Erythema score 1 was observed in all animals, which were fully reversible within 48 hours in 5/6 animals. In one animal erythema score 1 persist at study termination at the 72 hour reading. Although, because of the short recovery period, not proved, full reversibility is very likely if the observation period would have been extended to up to 14 days, as required according to recent guidelines, especially taking results from AAPB studies with higher concentrations into account. No edema was observed in this study.

AAPBs are technically processed as aqueous solutions or dry solids. Results described above show that up to and including the almost highest concentrated aqueous solutions of technically relevance (35 % a.i.) and as dry solids, AAPBs caused only slight transient skin irritation.

Supporting data are available from studies on aqueous dilutions with up to 38 % a.i. and 24 hour occlusive exposure. Under these intensive exposure conditions clear signs of skin irritation were observed. However, these data are not relevant for classification and labelling purpose, as the exposure regime does not meet the requirements of recent OECD guideline 404 and EU Method B.4.

In humans, Coco AAPB (30 % a.i., diluted to 3 % v/v) was not irritating following a single occlusive application for 24 hours.

 

Eye irritation/corrosion

In the key studies on primary eye irritation, performed according or similar to EU Method B.5 and/or OECD Guideline 405, 0.1 g or 0.1 mL of the test items was instilled into the conjunctival sac of rabbits. The eyes were not rinsed after test substance instillation. Irritation was scored according to the method of Draize for up to 21 days or full reversibility was reached.

Two studies were performed with spray dried solids. Coco AAPB (99.4 % dry solids) was instilled into the conjunctival sac of one rabbit. The treated eye showed 1 h after dosing extreme bleeding of conjunctivae and nictating membrane, blood coloured discharge, reddened iris, cornea opacity score 2 of one half of the cornea, iritis score 1, conjunctival erytheme and chemosis score 3. The untreated control eye showed no abnormalities. After this initial scoring the animal was humanely killed because of severity of effects. In this study, Coco AAPB (99.4 % dry solids) caused irreversible effects on the eye. (see table below). In the second study on a spray dried AAPB sample, 3 rabbits were exposed to C8-18 AAPB(84 % a.i.). Observation period was 21 days.Delayed occurrence of cornea opacitiy (score 1 or 2) was seen in two animals, persisting to day 21 in one animal. Initial iritis score 1 was observed in all animals, in one animal the severity increased temporarily to score 2. Iritis was fully reversible in all animals at day 10. Conjunctival redness score 2 or 3 and chemosis score 3 was observed in all animals. Both effects decreased with time but were not fully reversible in two animals until study termination. C8-18 AAPB caused irreversible effects on the eye in this study (see table below).

Irreversible effects were also seen when Coco AAPB was tested as aqueous solution with 35 % a.i. or 25 % a.i. (see table below).

Whereas the 10 % a.i. aqueous solution was an eye irritant but caused no irreversible damage to the eye. Cornea opacity score 1 which affected in the individual animals one quarter of the cornea to the whole cornea was seen at the initial scoring 24 hours after treatment in all six animals. From the second scoring 48 hours after treatment onward, two animals were free of cornea opacity. In the other 4 animals cornea opacity was fully reversible at the 7 day scoring. Iritis score 1 was seen in all six animals at the 24 hour scoring, in 4/6 at the 48 hour scoring and in 2/6 at the 72 hour scoring. Iritis was fully reversible in all animals by the 7 day scoring. Conjunctival redness reduced from initial score 3 in 2/6 and score 2 in the remaining 4/6 animals to full reversibility in all animals by the 7 day scoring. Chemosis score 3 in 3/6, score 2 in 1/6 and score 1 in 2/6 animals was seen at the 24 hour scoring. At the 48 hour scoring 3/6 animals were already free of chemosis and full reversibility in all animals was reached by the 7 day scoring. Discharge was seen in all animals at the 24 hour scoring with intensity between score 1 to 3 and was finally fully reversible in all animals by the 7 day scoring as all other eye responses.

A well the 5 % a.i. aqueous solution was an eye irritant but caused no irreversible damage to the eye. All animals showed 1 hour after treatment, cornea opacity score 1 which affected one quarter of the cornea (area score 1). Until the 24 hour scoring cornea opacity worsened in one animal to score 2 and trespassed in all four animals to the whole cornea (area score 4). Cornea effects were fully reversible within 72 hours. Iritis was solely seen in two of the four animals at the 24 hour scoring. Conjunctival redness worsened in all animals from initial scores 1 or 2 to score 3 at the 24 and 48 hour scorings and was fully reversible in all animals at the 7 day reading. Maximal chemosis was seen at the 6 hour scoring with score 1 in one and score two in the other three animals and was fully reversible in all animals by the by the 96 hour scoring. All animals showed discharge formation, which had its maximum at the 6 hour scoring and was fully reversible in all animals 7 days after treatment.

Coco AAPB in a concentrations of 4.5 % a.i. caused only minimal transient eye effects. A total of 6 rabbits were treated. The animals were not rinsed after test substance instillation, whereas the eyes of the remaining three animals were rinsed 4 seconds after treatment. None of the animals developed cornea opacity or iritis. The unrinsed eyes showed 24 hours after treatment, conjunctival redness score 2, chemosis score 2 and discharge score 1 or 2. A decrease of symptoms was seen from the second scoring 48 hours after treatment onward. All effects were fully reversible in all animals with unrinsed eyes after 7 days. Rinsing reduced incidence and intensity of effects. At the initial scoring conjunctival redness score 1 and chemosis score 1 was seen in 2/3 animals and in addition one of these animals showed also discharge score 1. In animals with rinsed eyes all effects had completely disappeared 72 hours after treatment. In this study, the mean eye irritation values induced by Coco AAPB (4.5 % a.i. in water) are well below the values triggering a classification.

In studies with 3 % a.i. AAPB, the eye effects were also minimal, but full reversibility was not proved, as the studies were already terminated after 72 hours. However, complete reversibility can be hypothesized if the observation period would have been extended to up to 21 days, as required according to recent guidelines.

Available eye irritation studies on aqueous solutions of C8-18 AAPB (30.3, 29, 10 and 3 % a.i.) do not comply with the relevant guidelines, as the observation period was only 72 hours. Effects seen until termination in the studies with the 30.3, 10 and 3 % a.i. C8-18 AAPB solutions are comparable to the effects induced by comparable or corresponding Coco AAPB concentrations. However, in the test with the 29 % a.i. C8-18 AAPB solution markedly less severe responses occurred than induced by the 35 and 25 % a.i. Coco AAPB solutions.

 

Summary

In the key studies on primary dermal irritation, performed according to EU Method B.4 and/or OECD Guideline 404 on dry solid AAPBs (99.4 % a.i. (Coco) and 84 % a.i. (C8-18)) and AAPB samples covering the highest technically relevant aqueous concentrations (35 % a.i. (Coco) and 30 % a.i. (C8-18)), AAPBs are only very slightly irritating to the skin of rabbits. Mean values of skin reactions at 24, 48 and 72 h were less than those triggering classification. Also, all findings were fully reversible. Clear signs of skin irritation were seen in rabbits after occlusive and/or 24 hour exposure to AAPBs with concentrations of about 30 %.

Aqueous AAPB solutions with ≥25 % and the spray dried AAPB induced corneal and/or iris damage in rabbits which was still present in some animals at the end of the observation period of 21 days. 5 to 10 % solutions caused mild to moderate effects, which were all reversible within the observation period. AAPB concentrations ≤ 4.5 % caused only minimal transient eye effects with mean scores following grading at 24, 48 and 72 hours after instillation well below the values triggering a classification.

The comprehensive data on Coco AAPB and C8-18 AAPB is used for hazard/risk assessment and C&L purposes for the whole group of AAPBs. The skin and eye irritation potential of the whole group of AAPBs is assumed to be similar. Coco AAPB used for read across purposes for the whole group of AAPBs acts as worst case model substance, as it contains short chain fatty acid moieties as well as unsaturated moieties, fatty acid amounts which might have some increasing influence on the irritating activity.

 

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

 

Justification for read-across

For details on substance identity and detailed toxicological profiles, please refer also to the general justification for read-across given at the beginning of the CSR and attached as pdf document to IUCLID section 13.

This read-across approach is justified based on structural similarities. All AAPBs contain the same functional groups. Thus a common mode of action can be assumed.

The only deviation within this group of substances is a minor variety in their fatty acid moiety (chain length and degree of unsaturation), which may have an influence on the outcome of skin and eye irritation studies. However,Coco AAPB is used for read across purposes for the whole group of AAPBs acting as worst case model substance, as it contains short chain fatty acid moieties as well as unsaturated moieties, fatty acid amounts which might have some increasing influence on the irritating activity.

 

a. Structural similarity and functional groups

Alkylamidopropyl betaines (AAPBs) are – with the exception of C12 AAPB - UVCB substances (Substances of Unknown or Variable composition, Complex reaction products or Biological materials), which are defined as reaction products of natural fatty acids or oils with dimethylaminopropylamine and further reaction with sodium monochloroacetate. AAPBs are amphoteric surfactants, which are characterized by both acidic and alkaline properties.

 

Their general structure is:

 

R-C(O)-NH-(CH2)3-(N(CH3)2)+-CH2-C(O)O-

R = fatty acid moiety

 

The fatty acids have a mixed, slightly varying composition with an even numbered chain length from C8 to C18. Unsaturated C18 may be included. Consequently, the AAPBs differ by their carbon chain length distribution and the degree of unsaturation in the fatty acid moiety. However, Lauramidopropyl betaine (C12 fatty acid derivate) is the major ingredient of all AAPBs covered by this justification as listed in table 1 “Substance identities” of the general justification for read-across.

 

The substances under evaluation share structural similarities with common functional groups (quaternary amines, amide bonds and carboxymethyl groups), and fatty acid chains with differences in chain length and degree of saturation.

 

b. Differences

Differences in the irritating properties of the AAPBs could potentially arise from the following facts:

-Different amounts of different carbon chain lengths (carbon chain length distribution):

Higher amounts of higher chain lengths and corresponding lower amounts of lower chain length could result in a rising average lipophilicity. However, the main component for all AAPBs is C12 AAPB. Relevant effects are not to be expected.

- Different amounts of unsaturated fatty ester moieties:

Effects may be expected for e.g. physical state and for some toxicological endpoints, mainly local effects (e.g. irritation). However, data obtained withC8-18 and C18 unsatd. AAPB are regarded as worst case as the substancecontains short chain fatty acid moieties as well as unsaturated moieties, fatty acid amounts which might have some increasing influence on the irritating activity.

 

Comparison of irritation data

 

Endpoints

Source substance

Target substance

 

C8-18 and C18 unsatd. AAPB

C8-18 AAPB

Skin irritation, in vivo

key_99.4% dry solids_Skin irritation / corrosion:61789-40-0_8.1.1_HOECHST_1995_OECD_404


key study

 

OECD TG 404, in vivo, rabbit, Type of coverage: semiocclusive, spray dried, 99.4% a.i.


not irritating

 

Reliability: 1 (reliable without restriction), GLP

key_84% dry solids_Skin irritation / corrosion: 97862-59-4_8.1_THG_1991a

key study

 

OECD TG 404, in vivo, rabbit, Type of coverage: semiocclusive, spray dried, 84% a.i.

 

not irritating

 

Reliability: 1 (reliable without restriction), GLP

key_35% a.i._Skin irritation / corrosion: 61789-40-0_8.1.1_Hüls_1986_OECD 404

key study


comparable to OECD TG 404, in vivo, rabbit, Type of coverage: occlusive, 35% a.i. in water

not irritating

 

Reliability: 2 (reliable with restrictions), no GLP

 

key_30% a.i._Skin irritation / corrosion: 97862-59-4_8.1_THG_1990a

 

key study

 

OECD TG 404, in vivo, rabbit, Type of coverage: semiocclusive, 30% a.i. in water

 

not irritating

 

Reliability: 1 (reliable without restriction), GLP

 

Sup_30% a.i._Skin irritation / corrosion: 61789-40-0_8.1_Henkel_1986a

 

Supporting study

 

comparable to OECD TG 404, in vivo, rabbit, Type of coverage: occlusive, 30% a.i. in water

not irritating

 

Reliability: 2 (reliable with restrictions), GLP

2 further supporting studies available with 38% and 33.3% a.i., respectively

 

 

US FHSA Federal regulation: 16 CFR 1500.41, in vivo, rabbit,

24 h occlusive

 

inadequate for C&L purposes

 

Reliability: 2 (reliable with restrictions)

Eye irritation, in vivo

key_99.4% dry solids_Eye irritation: 61789-40-0_8.2.1_HOECHST_1995_OECD_405

 

Key study

 

OECD TG 405, in vivo, rabbit, spray dried, 99.4% a.i.

 

Category 1 (irreversible effects on the eye)

 

Reliability: 1 (reliable without restriction), GLP

key_84% dry solids_Eye irritation: 97862-59-4_8.2.1_Th_Goldschmidt_AG_1991b


Key study


OECD TG 405, in vivo, rabbit, spray dried, 84% a.i.

 

Category 1 (irreversible effects on the eye)

 

Reliability: 1 (reliable without restriction), GLP

key_35% a.i._Eye irritation: 61789-40-0_8.2.1_Hüls_1986_OECD 405

 

Key study

 

OECD TG 405, in vivo, rabbit, 35 % a.i. in water

 

Category 1 (irreversible effects on the eye)

 

Reliability: 2 (reliable with restrictions), no GLP

sup_29% a.i._Eye irritation: 97862-59-4_8.2.1_ EOC_Simon_1991

Supporting study

similar to OECD TG 405, in vivo, rabbit, 29 % a.i. in water

 

not irritating

 

Reliability: 2 (reliable with restrictions), no GLP

 

key_25% a.i._Eye irritation: 61789-40-0_8.2.1_Henkel_1987b_OECD 405

 

Key study

 

OECD TG 405, in vivo, rabbit, 25 % a.i. in water

 

Category 1 (irreversible effects on the eye)

 

Reliability: 2 (reliable with restrictions), GLP

 

key_10% a.i._Eye irritation: 61789-40-0_8.2.1_Stepan_1982d_FDRL

 

Key study

 

US FHSA Federal regulation: 16 CFR 1500.42, in vivo, rabbit, 10 % a.i. in water

 

Category 2A (irritating to eyes)

 

Reliability: 2 (reliable with restrictions), GLP

key_5% a.i _Eye irritation: 61789-40-0_8.2.1_Henkel_1986b_OECD 405

 

Key study

 

OECD TG 405, in vivo, rabbit, 5% a.i. in water

 

Category 2A (irritating to eyes)

 

Reliability: 1 (reliable without restriction), GLP

key_4.5% a.i._Eye irritation: 61789-40-0_8.2_GCC_1965

Key study

Similar to OECD TG 405, in vivo, rabbit, 4.5 % a.i. in water

 

not irritating

 

Reliability: 2 (reliable with restrictions), pre-GLP

Sup_10% a.i._Eye irritation: 61789-40-0_8.2.1_Stepan_1982c_FDRL

 

Supporting study


US FHSA Federal regulation: 16 CFR 1500.42, in vivo, rabbit, 10 % a.i. in water

 

not irritating

 

Reliability: 2 (reliable with restrictions), GLP

Sup_7.5% a.i._Eye irritation: 61789-40-0_8.2.1_THG_1977

Supporting study

similar to OECD TG 405, in vivo, rabbit, 7.5 % a.i. in water

 

not irritating

 

Reliability: 2 (reliable with restrictions), pre-GLP

 

In the key studies on primary dermal irritation, mean values of skin reactions at 24, 48 and 72 h were less than the cut-off values for classification i. e. < 2.3 (CLP) and < 2 (67/548/EEC) for erythema/eschar and edema in each individual animal. Also, all findings were fully reversible. Considering these results of reliable relevant and adequatein vivotests, a non-classification for skin irritation is justified.

In studies on primary eye irritation, AAPB with a.i. ≥ 25 % caused severe eye effects not expected or proved not to be fully reversible within 21 days. AAPBs have to be classified as irritant with R41 Risk of serious damage to eyes (Directive 67/548/EEC), respectively as eye irritant Category 1 with H318 Causes serious eye damage (Regulation (EC) No 1272/2008) and need to be labelled accordingly.

 

Quality of the experimental data of the analogues:

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

The skin irritation studies were conducted according to (or comparable to) OECD Guideline 404 or US FHSA Federal regulation 16 CFR 1500.41 and are reliable or reliable with restrictions (RL1-2).

The eye irritation studies were conducted according to (or comparable to) OECD Guideline 405 or US FHSA Federal regulation 16 CFR 1500.42 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.

 

Conclusion

Based on structural similarities of the target and source substance as presented above and in more detail in the general justification for read across, it can be concluded that the available data from the source substance C8-18 and C18 unsatd. AAPB are also valid for the target substance C8-18 AAPB.

C8 -18 and C18 unsatd. AAPB used for read across purposes acts as worst case model substance, as it contains short chain fatty acid moieties as well as unsaturated moieties, fatty acid amounts which might have some increasing influence on the irritating potential.

Based on the mean values of skin reactions at 24, 48 and 72 h which were blow the cut-off values for classification i. e. < 2.3 (CLP) and < 2 (67/548/EEC) for erythema/eschar and edema in each individual animal and the full reversibility of the observed effects, a non-classification for skin irritation is justified.

Aqueous AAPB solutions with ≥25 % and the spray dried AAPB induced corneal and/or iris damage in rabbits which was still present in some animals at the end of the observation period of 21 days. 5 to 10 % solutions caused mild to moderate effects, which were all reversible within the observation period. AAPB concentrations ≤ 4.5 % caused only minimal transient eye effects with mean scores following grading at 24, 48 and 72 hours after instillation well below the values triggering a classification.

Justification for classification or non-classification

Skin irritation

A classification of AAPB is not justified for skin irritation according to CLP (EU-GHS) Regulation (EC) No 1272/2008 as well as the former European directive on classification and labelling 67/548/EEC.

Classification of skin irritation is based on erythema/eschar and edema calculated as mean scores following grading at 24, 48 and 72 hours after removal of the test material, in consideration of reversibility.

Results were taken from the key studies on primary dermal irritation, performed according to EU Method B.4 and/or OECD Guideline 404 on dry solid AAPBs (99.4 % a. i. (Coco) and 84 % a. i (C8-18)) and on AAPB samples covering the highest technically relevant aqueous concentrations (35 % a. i. (Coco) and 30 % a. i. (C8-18)). Mean values of skin reactions at 24, 48 and 72 h were less than the cut-off values for classification i. e. < 2.3 (CLP) and < 2 (67/548/EEC) for erythema/eschar and edema in each individual animal. Also, all findings were fully reversible. Considering these results of reliable relevant and adequatein vivotests, a non-classification for skin irritation is justified.

Eye irritation

A classification of AAPB is justified for eye irritation according to CLP (EU-GHS) Regulation (EC) No 1272/2008 as well as the former European directive on classification and labelling 67/548/EEC.

In studies on primary eye irritation, performed according to EU Method B.5 and/or OECD Guideline 405, AAPB with a. i. ≥ 25 % caused severe eye effects not expected or proved not to be fully reversible within 21 days. AAPBs have to be classified as irritant with R41 Risk of serious damage to eyes (Directive 67/548/EEC), respectively as eye irritant Category 1 with H318 Causes serious eye damage (Regulation (EC) No 1272/2008) and need to be labelled accordingly.

According to article 10 of GHS Regulation EC No 1272/2008, specific concentration limits (SCL) were established for AAPBs, which are above the general default concentration limit set for irritation Category 1 and Category 2 in Part 2 of Annex I of this regulation.

Aqueous solutions with 5 to 10 % a. i. of AAPB caused mild to moderate effects, which were all fully reversible within the observation period. Conjunctival redness mean scores following grading at 24, 48 and 72 h after instillation trigger a classification as eye irritant Category 2 according to CLP (EU-GHS) Regulation (EC) No 1272/2008 (mean scores following grading at 24, 48 and 72 hours after instillation of the test material for conjunctival redness2 in 4/4 animals in a study with 5 % a. i. and 3/6 in one study with 10 % a. i.). A classification with R36 according the former European directive on classification and labelling 67/548/EEC is not required since the cut-off value of 2.5 for conjunctival redness defined in this regulation is exceeded in the studies with 5 % and 10 % a. i. in only 2/4 and 2/6 animals, respectively (classification is indicated when the cut-off value is reached in 2/3 animals).

For AAPB concentrations4 % a classification as eye irritant is not justified, as AAPB in this concentration caused only minimal transient eye effects with mean scores following grading at 24, 48 and 72 hours after instillation well below the cut-off values for classification.

According to article 10 of GHS Regulation EC No 1272/2008, for eye irritation Category 1 a specific concentration limit (SCL) of > 10 % and for eye irritation Category 2 a SCL of > 4 % - ≤ 10 % could be established for mixtures containing AAPB. This implies, mixtures containing ≤ 4 % AAPB need not to be classified for eye irritation.