Registration Dossier

Administrative data

Description of key information

in vitro data

OECD 439: irritant

OECD 431: corrosive

in vivo data

Read Across OECD 404: negative

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
non GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Details on animal used as source of test system:
SOURCE ANIMAL
- Source: Gaukler, Offenbach, Germany
- Sex:male
- Housing:stainless stell cage with wire mesh walk floors, floor area: 40x51 cm
- Diet (e.g. ad libitum): Kliba 341, 4 MM (Klingentalmuehle AG, Kaiseraugst, Switzerland
- Water (e.g. ad libitum):about 250 mL tap water per day
- Acclimation period:at least 8 days before the beginning of the study
Vehicle:
water
Control samples:
other: untreated skin of the same animal served as control
Amount/concentration applied:
THE TEST PATCH (2.5 CM X 2.5 CM) WAS COVERED WITH AN APPROX. 0.5 MM LAYER OF AN 80% SUSPENSION (THUS ABOUT 0.5 G OF THE SUSPENSION WAS APPLIED
Duration of treatment / exposure:
4 h
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: GAUKLER; D-6050 OFFENBACH/MAIN, FRG
- Age at study initiation:
- Weight at study initiation: 2.71 kg
- Housing: single in CAGE MADE OF STAINLESS STEEL WITH WIRE MESH WALK FLOORS, FLOOR AREA: 40 CM X 51 CM
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 h

IN-LIFE DATES: From: To:
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
0.5 g of an 80% aqueous suspension on 2.5 cm x 2.5 cm area
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3 (m)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: 100 %
- Type of wrap if used: FOUR LAVERS OF ABSORBENT GAUZE + PORGUS BANDAGE).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after exposusure period with Lutrol and Lutrol/water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 4, 24, 48, 72 h after application

SCORING SYSTEM:
- Method of calculation: erythema and edema scores, calculation according toi 83/467/EEC criteria
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 4h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Other effects:
no other effects have been observed
Interpretation of results:
GHS criteria not met
Conclusions:
This OECD 404 compliant assay shows no irritation to skin after 4 h exposure of a test material suspension (80 % in water).
Executive summary:

This OECD 404 compliant assay shows no irritation to skin after 4 h exposure of a test material suspension (80 % in water).

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 10, 2016 - August 12, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Designation: Art. 806913
Synonym: DL-Mandelic acid for synthesis
Appearance: Solid
Minimum shelf life: May 31, 2020
Storage: Tightly closed, dark at room temperature (15 to 25°C)

Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
yes, concurrent positive control
Amount / concentration applied:
750 µL (i.e. 150mg/750µL) of test item preparation, negative or positive control.

The test item Art. 806913 was prepared as a 20% (w/v) suspension in a 0.9% sodium chloride solution. The stability in the vehicle was not investigated. The test item preparation was administered within <1 hour after preparation.
Duration of treatment / exposure:
240 minutes
Number of animals or in vitro replicates:
in vitro: triplicate design
Irritation parameter:
in vitro irritation score
Run / experiment:
Experiment 1 / Run 1
Value:
199.8
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation

Opacity
Permeability
IVIS
per cornea
per group
(mean value)
SD
Negative control
0.9% NaCl Solution
1.487
-0.001
1.477
1.2
1.1
-0.131
0.002
-0.106
2.067
0.002
2.102
Positive control
20% Imidazole solution
65.778
2.136
97.811
102.6
10.1
61.921
2.261
95.834
77.183
2.470
114.226
Test item
Art. 806913
202.722
0.002
202.745
199.8
6.5
204.439
-0.003
204.397
192.282
0.003
192.330


Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the conditions of the present study, Art. 806913 is inducing serious eye damage (UN GHS: Category 1).
Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. Under the conditions of the present study, Art. 806913 is inducing serious eye damage (UN GHS: Category 1).

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

Additional information

For this endpoint information from a structural similar compound is available. The study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 404. The test material was the enantiomer of mandelic acid providing highest simlarity in terms of chemical, biological and physicochemical parameters. Therefore using the in vivo data of the enantiomer for the racemic mixture is justified.

Justification for classification or non-classification

For this endpoint in vivo data are available. In this in vivo study perfomred for the enantiomer no indication for irritation was demonstrated. Therfore, the in vitro findings are considered not relevant for the in vivo situation and no classification is warranted.