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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional 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.) of aqueous C8-18 AAPB are available.

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 with25 % 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 21days. 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.

Relevant data in detail

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 thoughCoco 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 onewhite 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.


Effects on eye irritation: corrosive

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.