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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-04-01 to 2018-04-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2017-10-09
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2015-06-05

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- State of aggregation: solid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: dry, < 30 °C

Due to the intrinsic properties of the test material direct application according to the OECD Guideline number 405 (neat or grounded to fine dust) was technically not feasible. The test material is hygroscopic. After preparation of a solution with ground test material it immediately clumped. For this reason it is assumed, that the ground test material immediately clumps after direct application into the eye.
So the test material was suspended with aqua ad injectionem at a concentration of 40 g/L in order to obtain a saturated aqueous solution (the water solubility of the test material is approximately 33 g/L). The suspension was incubated under agitation for 48 hours at room temperature.
After 48 hours the suspension was centrifuged and the saturated aqueous solution of Barium 4-dodecylphenolate was administered.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 47 or 48 weeks old
- Weight at study initiation: 4.0 – 4.4 kg
- Housing: housed in ABS-plastic or Noryl rabbit cages, floor 4200 cm2
- Diet (ad libitum): autoclaved hay and to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Relative humidity: 55 ± 10%
- Air changes: at least 10 x / hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
other: aqua ad injectionem
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the saturated aqueous solution of Barium 4-dodecylphenolate
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
1 hour as well as 24, 48 and 72 hours after test item application
Number of animals or in vitro replicates:
2 female rabbits
Details on study design:
INITIAL AND CONFIRMATORY TEST
The in vivo test was performed initially using one animal. Since the results of the initial test did not indicate the saturated aqueous solution of Barium 4-dodecylphenolate of the test item to be corrosive or a severe irritant to the eye using the procedure described. In order to confirm the response, one additional animal was treated in the same manner.

USE OF TOPICAL ANESTHETICS AND SYSTEMIC ANALGESICS
One hour before the application of the saturated aqueous solution of the test item, 0.01 mg/kg of buprenorphine (Temgesic® 0.3 mg/mL) was administered subcutaneously in order to achieve a therapeutic level of systemic analgesia.
Approx. 5 minutes prior to the application of the saturated aqueous solution of the test item, 1-2 drops of an ocular anaesthetic (Proparakaine-POS® hydrochloride ophthalmic 0.5% solution) were administered in both the treated and the control eye of each animal.
Post-application the animals did not show pain and distress and therefore did not receive analgesia.

REMOVAL OF TEST SUBSTANCE
- Washing: eyes were not rinsed to remove residues of the test item supernatant, foreign bodies or incrustation 1 hour after application.

SCORING SYSTEM: according to the Draize scale

TOOL USED TO ASSESS SCORE: slit lamp biomicroscope / fluorescein solution
To detect cornea lesions the treated eyes were examined with the aid of a fluorescein solution and a slit lamp biomicroscope 24 hours post-application and from then on daily until end of the observation period. The eyes were rinsed with physiological saline 0.9% NaCl after the examination.

OBSERVATIONS
- body weight: prior to the administration and at the end of the observation period
- nature, severity and duration of clinical observations were described (systemic effects and local effects)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Initial animal:
The animal showed slight conjunctival redness (score 1) from 1 hour until 24 hours post-application. The effect was fully reversible within 48 hours after application of the test material. The mean score of the animal, following grading at 24, 48 and 72 h after installation of the test material’s supernatant, was calculated to be 0.33.
Iris, conjunctiva and cornea were not affected by administration of the saturated aqueous solution of the test item.

Confirmatory animal:
The animal showed slight conjunctival redness (score 1) from one hour until 24 hours post-application. The effect was fully reversible within 48 hours after application of the test material. The mean score of the animal, following grading at 24, 48 and 72 h after installation of the test material’s supernatant, was calculated to be 0.33.
Iris, conjunctiva and cornea were not affected by administration of the saturated aqueous solution of Barium 4-dodecylphenolate.

Other effects:
- clinical observations: neither mortalities nor significant clinical signs of toxicity were observed in any animal. Local effects were only found in the confirmatory animal, which showed 1 hour post-application redness on the nictitating membrane. The observed effect fully disappeared within 24 hours.
- body weight: the body weight development of all animals was within the expected range.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The saturated aqueous solution of barium 4-dodecylphenolate is not irritating to the eyes.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the saturated aqueous solution of barium 4-dodecylphenolate does not require classification as eye irritant.