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Administrative data

Description of key information

Concerning skin and eye irritation, MATMD was tested with NZW rabbits. There are no data available concerning respiratory irritation. However, as MATMD has irritant and corrosive properties, a study concerning respiratory irritation with exposure via inhalation is scientifically unjustified.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in compliance with GLP and according to the OECD guideline 404 (acute skin irritation/corrosion).
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 14 weeks, females 15 weeks
- Weight at study initiation: males 2.4-2.6 kg, females 2.5 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: The test article was applied moistened with polyethylene glycol (PEG 400)
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
The skin reaction was assessed at 1, 24, 48 and 72 hours and at 7 days intervals after the removal of the dressing, gauze patch and test article.
Number of animals:
3
Details on study design:
TEST SITE:
Approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square
centimeters ( 10 cm x 10 cm) .
On test day 1, 0.5 g of the test article was applied to approx. 6 cm2 of the intact skin of the shaved area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an
elastic bandage.
REMOVAL OF TEST SUBSTANCE:
Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
male
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
male
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
female
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
male
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
male
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
female
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Irritation:
MATMD showed a primary irritation score of 2.67, when applied to intact rabbit skin. Local signs (mean 1 hour to 7 days) consisted of grade
1.5 erythema and grade 0.6 edema. They were reversible until day 7.
Corrosion:
No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin. Slight scales were
observed in two animals, and moderate scales were observed in one animal on day 7 of observation.
Other effects:
Coloration:
In the area of application, brown staining of the treated skin by pigment or coloring of the test article was observed in all animals at each of the
measuring intervals.
Body weights:
The body weight gain of all rabbits was similar.
Clinical symptoms / Mortality:
No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.
Necropsy:
No necropsy was performed. All animals were killed and discarded.
Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Due to the mean irritation score of 2.67 when applied to the intact skin of rabbits the substance had to be classified as an irritant to the skin.
Executive summary:

Due to the mean irritation score of 2.67 when applied to the intact skin of rabbits the substance had to be classified as an irritant to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in compliance with GLP and according to the OECD guideline 405 (acute eye irritation/corrosion).
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
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 14 weeks, females 15 weeks (at start of treatment)
- Weight at study initiation: males 2.6 - 2.7 kg, females 2.0 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal served as control
Amount / concentration applied:
0.1 g / animal
Duration of treatment / exposure:
Single exposure, no washing
Observation period (in vivo):
1, 24, 48 and 72 hours, 7, 14 and 21 days after administration.
Number of animals or in vitro replicates:
3
Details on study design:
The test article (0.1 g per animal) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the
eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served
as the reference control. The eyes of each animal were examined 1, 24, 48 and 72 hours, and at 7, 14 and 21 days after administration.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48 and 72 hours
Score:
0.88
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48 and 72 hours
Score:
2.22
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 1-3
Time point:
other: 24, 48 and 72 hours
Score:
3.11
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Partly corrosion of the conjuctivae was observed ·in all animals from 24 hours to 7 days after treatment.
Other effects:
No staining of the cornea and conjunctivae of the treated eyes by pigment or coloring of the test article was observed.
Corneal opacity was observed in two animals from 1 hour to 21 days, and in one animal from 24 hours to 21 days after test article application.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this experiment, MATMD was found to cause a primary irritation score of 8.17, when applied to the conjunctival sac of the
rabbit eye.
Executive summary:

In all 3 animals (in 2 from 1 hour and in 1 from 24 hours after administration) irreversible corneal opacity was noted and hence the substance had to be classified as inducing irreversible changes to the eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Concerning skin irritation, MATMD was tested with NZW rabbits according to OECD guideline 404 with GLP compliance. Due to the mean irritation score of 2.67 when applied to the intact skin, the substance had to be classified as an irritant to the skin.

Concerning eye irritation, MATMD was tested with NZW rabbits according to OECD guideline 405 with GLP compliance. In all 3 animals (in 2 from 1 hour and in 1 from 24 hours after administration) irreversible corneal opacity was noted and hence the substance had to be classified as inducing irreversible changes to the eye.

In a 28 day gavage study, several necrotic/inflammatory lesions and/or reactive alteration to the local injuries were recorded in trachea, lung and/or oesophagus. These findings were unlikely to be lesions resulting from the systemic exposure of the test item and were considered to be secondary or incidental events caused by regurgitation and/or incidental aspiration of the test item. Also the high viscosity of the vehicle PEG is known to induce a physical reflux after gavage dosing. In addition MATMD was shown to be irritant to the skin and corrosive to the eye in studies with NZW rabbits. Therefore a study concerning respiratory irritation with exposure via inhalation is scientifically unjustified.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification