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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
30 April 2015 to 14 May 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For read across justification, see Section 13 of IUCLID

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Dilithium adipate
EC Number:
242-449-7
EC Name:
Dilithium adipate
Cas Number:
18621-94-8
Molecular formula:
C6H8O4.2Li
IUPAC Name:
dilithium adipate
impurity 1
Chemical structure
Reference substance name:
Adipic acid
EC Number:
204-673-3
EC Name:
Adipic acid
Cas Number:
124-04-9
Molecular formula:
C6H10O4
IUPAC Name:
adipic acid
Test material form:
solid
Details on test material:
- Batch number: A049-99
- Expiry date: 06 March 2018
- Storage condition of test material: At room temperature protected from light

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L'Arbresle Cedex, France
- Age at study initiation: 24 - 26 weeks old
- Weight at study initiation: 4322 - 4981 g
- Housing: Individually housed in labeled cages with perforated floors (dimensions: 67 x 62 x 55 cm, Ebeco, Germany) and shelters (dimensions: 40 x 32 x 23 cm, Ebeco, Germany).
- Diet: Pelleted diet for rabbits (Global Diet 2030, Harlan Tekland, Mucedola, Milanese, Italy), approximately 100 g per day. Hay (Tecnilab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period.
- Water: Tap water, ad libitum.
- Acclimation period: At least 5 days before test start, under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 24 °C
- Humidity: 40 - 70 %
- Air changes: at least 10 air changes/hour
- Photoperiod: 12 hours dark: 12 hours light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: Animals were treated by instillation of 27.8 mg (range 27.4 - 28.3 mg) of the test substance (a volume of approximately 0.1 mL) in the conjunctival sac of one eye after gently pulling the lower lid away from the eyeball. The second eye remianed untreated and served as the control.

Duration of treatment / exposure:
Single application.
Observation period (in vivo):
Observations of eyes: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.
Observations were made twice daily for mortality/viability and at least once daily for toxicity. Body weight was measured prior instillation of test item and after the final observation.
Number of animals or in vitro replicates:
3 females. The study was performed in a stepwise manner and was started by treatment of a single rabbit. Two other animals were treated in a similar manner 11 days later, after considering the degree of eye irritation observed in the first animal.
Details on study design:
PREEMPTIVE PAIN MANAGEMENT
One hour prior to instillation of the test substance, buprenorphine (Buprenodale®, Dechra Ltd., Stoke-on-
Trent, United Kingdom) 0.01 mg/kg was administered by subcutaneous injection in order to provide
a therapeutic level of systemic analgesia.

Five minutes prior to instillation of the test substance, two drops of the topical anesthetic alcaine 0.5%
(SA Alcon-Couvreur NV, Puurs, Belgium) were applied to both eyes.

Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic
analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH,
Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection.

REMOVAL OF TEST SUBSTANCE: None.

SCORING SYSTEM: The irritation was assessed according to the numerical scoring system. At each observation, the highest scores given were recorded.

TOOL USED TO ASSESS SCORE: 2 % fluorescein (Merck, Germany) in water (adjusted to pH 7.0)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 24 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
- Corneal effects: None were noted during the study
- Iridial effects: No iridial irritation observed during the study.
- Conjunctival effects: Irritation of the conjunctivae, which consicted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in all animals.
Other effects:
No signs of systemic toxicity observed in the animals during the test period and no mortality occured.

Any other information on results incl. tables

Table 1. Individual eye irritation scores

Animal

Time after dosing (h)

Cornea

Iris

Conjunctivae

Comments

Opacity (0-4)

Area (0-4)

Fluor area (%)2

(0-2)

Redness (0-3)

Chemosis (0-4)

Discharge (0-3)

43

1

0

0

0

0

2

2

1

-

24

0

0

0

2

1

0

-

48

0

0

0

1

0

0

-

72

0

0

0

0

0

0

-

2

1

0

0

0

0

2

1

1

-

24

0

0

0

1

0

0

-

48

0

0

0

1

0

0

-

 72

0

0

0

0

0

0

-

84

1

0

0

0

0

2

1

1

-

24

0

0

0

1

0

0

-

48

0

0

0

1

0

0

-

72

0

0

0

0

0

0

-

Table 2. Animal specification

Animal

Sex

Age at start (weeks)

Body weights (g)

 

Prior to application

At termination

43

female

24

4867

4918

2

female

25

4322

4359

84

female

26

4991

4985

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Dilithium adipate does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.
Executive summary:

The eye irritation of dilithium adipate was assessed in a GLP-compliant, in vivo eye irritation study following OECD guidelines 405 (WIL Research 2015). A single treatment of dilithium adipate was applied to the non-irrigated eye of three rabbits and observations made at 1, 24, 48 and 72 hours for effects on conjunctivae, iris and cornea and for reversibility of effects.

Instillation of the dilithium adipate resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in all animals. Based on the results, dilithium adipate does not have to be classified for eye irritation according to GHS and Regulation EC No. 1272/2008.

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