Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 02 Oct 2007 to 08 Jan 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to international test guidelines and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:
Harlan Netherlands BV
Kreuzelweg 53, NL-5961 NM Horst/The Netherlands
Postbus 6174, NL-5960 AD Horst/The Netherlands
- Age at study initiation: 11 weeks for the male; 13-14 weeks for the females
- Weight at study initiation: 2445 to 2778 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 08/07, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet, batch no. 31/07 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23° C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (music during the daytime light period)

IN-LIFE DATES: From: 15 Oct 2007 to 18 Oct 2007

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied : 0.1 mL/animal
- Concentration: 100%
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
1, 24, 48 and 72 hours after administration
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing done.

SCORING SYSTEM: according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004. Scleral reddening and ocular discharge were also assessed.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
other: overall at 24, 48 and 72 h
Score:
0.22
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Meaof each animal: 0.33; 0.33; 0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
The test material did not induce significant or irriversible damage to the rabbit eye.

The grade 2 conjunctival redness was observed in all 3 animals at the 1-hour reading time and this effect was still observed (with grade 1) in 2 animals at 24 hours, but was no longer present at 48 hours.

A slight reddening of the sclerae was present in both females at the 1-hour evaluation.
Other effects:
No other local signs and no staining observed.

No clinical signs and body weights were within the normal range.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

(redness)

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

2/2/2 

0/0/0

24 h

0/0/0

0/0/0

 1/1/0

0/0/0

48 h

0/0/0

0/0/0

 0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0/0/0 

0/0/0

 0.33/0.33/0

0/0/0

Reversibility*)

 -

-

 c (48 hours)

-

 

*) Reversibility: c. = completely reversible.

 

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), Dimethyl 2-methylglutarate is considered to be "not irritating" to the rabbit eye.
Executive summary:

In an eye irritation study, 3 New Zealand White rabbits were treated by an ocular instillation of 0.1 mL of undiluted Dimethyl 2-methyl glutarate and were observed 1, 24, 48 and 72 hours after administration.

 

The instillation of the test material into the eye resulted in mild to moderate, early-onset (from 1-hour post-administration) and transient ocular changes, including reddening of the conjunctivae and sclerae (maximum mean score of 0.33 for the conjunctivae). These effects were reversible and no longer evident 24- or 48 hours after treatment.

 

No other local signs and no staining were observed. There were no clinical signs and body weights were within the normal range.

 

This ocular irritation study is classified as acceptable. It does satisfy the guideline requirement for an acute ocular irritation/corrosion study (OECD 405) in the rabbit.