Benzeneacetic acid, .alpha.-hydroxy-, ammonium salt (1:1), (.alpha.R)-

Endpoint summary

Description of key information

Skin: not irritating (BASF, 2001)
Eye: irritating (BASF, 2016a)

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)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The potential of (R)-Ammoniummandelat-Lösung (ca. 30%) to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 White New Zealand rabbits for 4 hours under semiocclusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed approximately 1, 24, 48, 72 hours and 7 days after removal of the patch. Slight to moderate erythema was observed in all animals on the day of application, slight erythema persisted in 1 animal up to day 3. No edema was observed. The cutaneous reactions were reversible in all animals within 7 days after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.3 for erythema and 0.0 for edema. Considering the described cutaneous reactions as well as the average score for irritation, (R)-Ammoniummandelat-Lösung (ca. 30%) does not give indication of an irritant property to the skin under the test conditions chosen (BASF, 2001).

D-(-)-Mandelic acid was tested in an acute dermal irritation/corrosion test (according to OECD 404). No skin reaction was noted at any reading 1, 24, 48, or 82 h after semiocclusive dermal exposure to 0.5 g of the test substance (80% aqueous formulation) for 4 h in any of 3 White Vienna rabbits (BASF 1987).

Even under worst case conditions using mandelic acid, no skin reactionwas observed. Therefore, Benzeneacetic acid, .alpha.- hydroxy-, monoammonium salt, (.alpha.R) does not pose a skin irritating potential.

Eye Irritation 

Several studies are available for Benzeneacetic acid, .alpha.- hydroxy-, monoammonium salt, (.alpha.R). A study (OECD 405) with the 30% aqueous solution of (R)-Ammoniummandalte does not give indication of an irritant property to the eye under the test conditions chosen (BASF, 2001). To assess the properties of the pure substance, an in vitro test (BCOP) was performed using dried test substance. This test gave a borderline result, which does not clearly allow the evaluation of the risk to cause serious eye damage. Based on the observed results and applying the evaluation criteria it was concluded, that the results of the test substance Benzeneacetic acid, .alpha.- hydroxy-, monoammonium salt, (.alpha.R)- (dried) have to be considered “inconclusive” in the Bovine Corneal Opacity and Permeability Test (BCOP Test) under the test conditions chosen (BASF, 2016a). To perform a final assessment an additional OECD 405 guideline study was performed also with the dried test substance (saturated solution, BASF, 2016b).

The potential of Benzeneacetic acid, .alpha.-hydroxy-, monoammonium salt, (.alpha.R)- (dried) to cause ocular irritation or serious damage to the eyes (BCOP, OECD 437) was assessed by a single topical application of 750μL of a 20% test-substance preparation to the epithelial surface of isolated bovine corneas.Three corneas were treated with the test-substance preparation for an exposure period of 4 hours.

The mean In Vitro Irritancy Score was 59.7. The borderline result do not clearly allow for the evaluation of risk of serious eye damage. On basis of the results of this study a potential of the test substance to bear a risk of serious eye damage cannot be excluded.

Based on the observed results and applying the evaluation criteria it has to be concluded, that the results of the test substance Benzeneacetic acid, .alpha.- hydroxy-, monoammonium salt, (.alpha.R)- (dried) should be considered “inconclusive” in the Bovine Corneal Opacity and Permeability Test (BCOP Test) under the test conditions chosen (BASF, 2016a). For final assignment of a risk phrase at present, results from another study would be needed.

The potential of Benzeneacetic acid, .alpha.-hydroxy-, monoammonium salt, (.alpha.R)- (dried) to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL of the saturated solution of the test item to one eye of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About, and not less than 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and in a weekly interval until day 7. Additional eye examinations were performed following the instillation of a fluorescein solution starting at 24 h after administration until hour 48 in two animals or day 7 in one animal (reversibility of corneal lesions).

Clinical observations were recorded during the course of the study: Slight corneal opacity (grade 1), moderate iritis (grade 1), slight to obvious conjunctival redness (grade 1-2), slight to moderate conjunctival chemosis (grade 1-2), slight to severe discharge (grade 1-3), additional findings like desquamation of corneal epithelium, corneal lesions detected with the aid of fluorescein (grade 1, 2 and 4) and injected scleral vessels in a circumscribed or circular area were noted in the animals within 7 days after application. The ocular reactions were reversible in all animals within 7 days after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 0.0 and 0.0 for corneal opacity, 0.3, 0.0 and 0.0 for iris lesions, 2.0, 1.0 and 2.0 for redness of the conjunctiva and 1.3, 1.0 and 1.7 for chemosis.

Considering the described ocular reactions as well as the average score for irritation, Benzeneacetic acid, .alpha.-hydroxy-, monoammonium salt, (.alpha.R)- (dried) shows an eye irritating potential under the test conditions chosen. (BASF, 2016b)

The potential of (R)-AmmoniummandeIat-Lösung (ca. 30%) to cause damage to the conjunctiva, iris or cornea was assessed in 3 White New Zealand rabbits, subjected to a single ocular application of 0.1 ml of the test substance. About 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Slight to moderate conjunctival redness was observed in the animals up to 48 hours after application. Additionally slight conjunctival swelling was noted in 1 animal and slight discharge in 2 animals on the day of application. No other ocular findings were noted. The ocular reactions were reversible in all animals within 72 hours after application at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, iris and chemosis and 0.4 for conjunctival redness.Considering the described ocular reactions as well as the average score for irritation, (R)-AmmoniummandeIat-Lösung (ca.30%) does not give indication of an irritant property to the eye under the test conditions chosen (BASF, 2001).

Justification for selection of skin irritation / corrosion endpoint:
key study

Justification for selection of eye irritation endpoint:
Key study

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the results of the eye irritation testing, the test item is classified as eye irritant cat. 2 (H319) according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.