Registration Dossier

Administrative data

Description of key information

On each of the two endopoints skin and eye irritation, two in-vivo studies have been carried out with 2.5% and 50% aqueous solutions of target chemical toluene-2,5-diamine. No skin irritation effects observed, however the classificationas eye irritant would apply for 50% aqueous solutions of target chemical toluene-2,5-diamine.

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:
1994-05-05 to 1994-12-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline-conform study under GLP. Evaluation of erythema was not possible due to staining effects caused by the test item, thus unambiguously clear conclusions cannot be drawn from the available data. The study therefore is considered as reliable with restrictions.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France- Age at study initiation: no data- Weight at study initiation: 2.4 +/-0.1 kg- Housing: individually in polystyrene cages- Diet (e.g. ad libitum): pelleted diet ad libitum- Water (e.g. ad libitum): drinking water filtered by a F.G Millopore membrane (0.22 microns) provided ad libitum - Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18 +/- 3 °C- Humidity (%): 30 - 70 %- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): 12 h / 12 hIN-LIFE DATES: From: 1994-05-20 To: 1994-05-30
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL- Concentration (if solution): 50.6 %VEHICLEnot applicable
Duration of treatment / exposure:
4 h
Observation period:
6 d
Number of animals:
3
Details on study design:
TEST SITE- Area of exposure: right flank- % coverage: test substance was applied to a 6 cm2 gauze patch, which then was applied to the right flank- Type of wrap if used: test substance and gauze patch were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage REMOVAL OF TEST SUBSTANCE- Washing (if done): substance was removed with a gauze patch moinstened with paraffin oil- Time after start of exposure: 4 hSCORING SYSTEM:Erythem and eschar formation:no erythema: 0very slight erythema: 1well-defined erythema: 2moderate to severe erythema: 3very erythema (beet redness) to slight eschar formation (injuries in depth): 4Oedema formation:no oedema: 0very slight oedema: 1slight oedema: 2moderate oedema (raised approx. 1 mm): 3severe oedema (raised more than 1 mm and extending beyong the area of exposure): 4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: over all time points
Score:
0
Max. score:
0
Irritation parameter:
other: ulceration or necrosis
Basis:
mean
Time point:
other: over all time points
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: over all time points
Reversibility:
no data
Remarks on result:
other: In all 3 animals black colouration of the treated site by residual test substance had prevented the evaluation of erythema over the 6 days observation period.
Irritant / corrosive response data:
None reported.
Other effects:
In all 3 animals black colouration of the treated site by residual test substance had prevented the evaluation of a well-defined and a moderate to severe erythema over the 6 days observation period.
Interpretation of results:
other: Development of erythema basically possible, however this could not be evaluated due to staining effects caused by the test item.
Remarks:
Criteria used for interpretation of results: not specified
Conclusions:
No oedema, ulceration or necrosis was being observed during the study period. According to the study report, it is being concluded that under the given experimental conditions the test item IMEXINE OD (still) could provoke moderate or severe irritant effects when administered by cutaneous route to rabbits, as erythema could not be evaluated due to skin staining effects caused by the test item.
Executive summary:

The purpose of the study was to evaluate the dermal irritation properties of test item IMEXINE DO, which contains 50.6% of target chemical toluene-2,5 -diamine in aqueous solution. the study followed the protocol as given by OECD Guideline 404. No oedema, ulceration or necrosis was being observed during the study period. In all 3 animals black colouration of the treated site by residual test substance had prevented the evaluation of a well-defined and a moderate to severe erythema over the 6 days observation period. Event though no actual dermal irritation effects were being noted in the study report, it is being concluded by the study director that under the given experimental conditions the test item IMEXINE OD could provoke moderate or severe irritant effects when administered by counateous route to rabbits, in this way taking into accout a worst case assumption.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-05-10 to 1994-08-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study without deviations, under GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France- Age at study initiation: no data- Weight at study initiation: 2.75 kg- Housing: individually in polystyrene cages- Diet (e.g. ad libitum): pelleted diet ad libitum- Water (e.g. ad libitum): drinking water filtered by a F.G Millopore membrane (0.22 microns) provided ad libitum - Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18 +/- 3 °C- Humidity (%): 30 - 70 %- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): 12 h / 12 hIN-LIFE DATES: From: 1994-06-25 To: 1994-06-08
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 mL- Concentration (if solution): 50.6 %VEHICLEnot applicable
Duration of treatment / exposure:
8 days (over the whole observation period, no rinsing of treated eye)
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCEnot doneSCORING SYSTEM: According to the study report, the classification was based on criteria laid down in Directive 91/325/ECC Commission Directive of 1st March 1991 adapting to the technical progress for the twelth time Council Directive 67/548/ECC. - Chemosis: scoring range 0 - 4- Redness: scoring range 0 - 3- Discharge: scoring range 0 - 3- Iritis: scoring range 0 - 2- Cornea opacity: scoring range 0 - 4- Cornea area of opacity: scoring range 0 - 4- 0: no effects observed; highest figures, respectively: most severe effects observed; inbetween grading by whole number steps TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: overall at 24, 48, and 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Remarks:
intensity of opacity
Basis:
animal #1
Time point:
other: overall at 24, 48, and 72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Remarks:
area of opacity
Basis:
animal #1
Time point:
other: overall at 24, 48, and 72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: overall at 24, 48, and 72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: overall at 24, 48, and 72 h
Score:
3.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: discharge
Basis:
animal #1
Time point:
other: overall at 24, 48, and 72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritant / corrosive response data:
in the study report, the study director names 24 h reading day 2, 48 h reading day 3, and 72 h day 4, etc. However it is considered appropriate to name the 24 h reading day 1, the 48 h reading day 2, and the 72 h reading day 3, etc., which is reflecting to the data presented in above table.
Other effects:
none
Interpretation of results:
irritating
Remarks:
Migrated information50.6% toluene-2.5-diamineCriteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions, test item IMEXINE OD (i.e. 50.6 % of target chemical toluene-2,5-diamine in aqeous solution) was considered as irritating to eye (category 2, as effects were fully reversible) when administered by ocular route to one rabbit.
Executive summary:

The purpose of this study was to evaluate the eye irritating potential of test item IMEXINE OD (i.e. 50.6 % of target chemical toluene-2,5-diamine in aqeous solution). The study followed the protocol as given by OECD Guideline 405. Only one rabbit was being treated with 0.1 mL of IMEXIDINE OD, without rinsing of the eye.

The most significant irritation scores as overall average of the 24 h, 48 h, and 72 h readings were as follows:

- Iritis: 1.0

- Corneal opacity (intensity): 1.3

- Conjunctival redness: 3.0

- Chemosis: 3.7

As all obseved irritating effects were fully reversible within 7 days, test item IMEXINE OD (i.e. 50.6 % of target chemical

toluene-2,5-diamine in aqeous solution) shall be considered as irritating to eyes category 2, H319, according to the CLP classification system, and as Xi; R36, irritating to eyes, according to the former DSD classification system.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

No oedema, ulceration or necrosis was being observed during the study period. According to the study report, it is being concluded that under the given experimental conditions the test item IMEXINE OD (still) could provoke moderate or severe irritant effects when administered by cutaneous route to rabbits, as erythema could not be evaluated due to skin staining effects caused by the test item.

Eye irritation:

Study on 2.5% toluene-2,5 -diamine:

No significant eye irritating effects were being observed.

Study on 50.6% toluene-2,5 -diamine:

Under the experimental conditions, test item 50.6 % of target chemical toluene-2,5-diamine in aqeous solution was considered as irritating to eye (category 2, as effects were fully reversible) when administered by ocular route to one rabbit.

Conclusion:

As temporary conclusion, based on the available data target chemical toluene-2,5 -diamine shall be considered as irritant to eyes. Without information of 100% test material, the worst case is supposed with highly irritant effect.


Justification for selection of skin irritation / corrosion endpoint:
weight on evidence based on two avaialble studies of reliability 2

Justification for selection of eye irritation endpoint:
Under the experimental conditions, test item IMEXINE OD (i.e. 50.6 % of target chemical toluene-2,5-diamine in aqeous solution) was considered as irritating to eye (category 2, as effects were fully reversible) when administered by ocular route to one rabbit.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation:

Based on data available at this point of time, no classification applicable, as no classification-relevant skin irritating effects were being observed in the studies

Eye irritation:

Based on data available from the study with 50% toluene-2,5 -diamine, following temporary classification for toluene-2,5 -diamine shall apply.

GHS/CLP: causes serious eye damage Category 1, H318

DSD: Xi; R41, Risk of seriuos damage to eyes