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Administrative data

Description of key information

In the key skin irritation study (Laboratoires de Recherches de la Societe des Usines, 1971), D4 was not irritating to rabbit skin. Furthermore, acute and repeated-dose dermal toxicity studies in rats showed no indication of adverse local effects on the skin of rats or rabbits (see Sections 7.2.3 and 7.5.2).

In the key eye irritation study (Dow Corning Corporation, 1997e) D4 was not irritating to the eyes of rabbits.  Repeated dose inhalation studies generally show signs of respiratory tract irritation.

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study report lacked many details regarding the test animals and environmental conditions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Not stated

- Age at study initiation: Not stated

- Weight at study initiation: 2.3 - 2.8 kg

- Housing: Not stated

- Diet (e.g. ad libitum): Not stated

- Water (e.g. ad libitum): Not stated

- Acclimation period: Not stated

ENVIRONMENTAL CONDITIONS

- Temperature (°C): Not stated

- Humidity (%): Not stated

- Air changes (per hr): Not stated

- Photoperiod (hrs dark / hrs light): Not stated
Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml to intact and abraded skin
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE

- Area of exposure: 4cm diameter

SCORING SYSTEM: Draize
Irritation parameter:
overall irritation score
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: No skin reactions were observed at any time for intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours.
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Other effects:
No data

No skin reactions were observed at any time for intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours.

Interpretation of results:
GHS criteria not met
Conclusions:
In a study that pre-dates GLP but was similar to OECD 404, D4 produced to skin reactions in intact with of rabbits. It is therefore not irritant according to EU criteria.
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:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
2 animals were used instead of 3
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Age at study initiation: adult

- Weight at study initiation: 3-4 kg

- Housing: Individually housed
Vehicle:
not specified
Controls:
other: Untreated eye
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.1ml

- Concentration (if solution): undiluted

Duration of treatment / exposure:
Single intillation, not rinsed.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): not rinsed


SCORING SYSTEM: Draize


Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
No eye irritation was observed.
Other effects:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to be not irritating in a reliable study conducted according to an appropriate test protocol. Not conducted according to GLP. Although only 2 animals were used instead of 3 as specified in the test guideline, this does not affect the outcome of the study since no effects were seen in the test animals.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In the key skin irritation study (Laboratoires de Recherches de la Societe des Usines, 1971) 0.5 ml of undiluted D4 was applied to the shaved skin (intact and abraded) of 6 albino rabbits for 24 hours. There was no information on the type of dressing used to hold the D4 in place. The animals were then observed for 72 hours for skin reactions and signs of toxicity. Skin reactions were scored according to the scoring system of Draize. No skin reactions were observed at any time in intact skin. For abraded skin, desquamation was observed but was fully resolved after 72 hours. Therefore, D4 was not irritating to the skin under the conditions of this study. Supporting studies confirm the conclusion that D4 is not a skin irritant. Furthermore, acute and repeated-dose dermal toxicity studies in rats showed no indication of adverse local effects on the skin of rats or rabbits.

In the key eye irritation study (Dow Corning Corporation, 1997e) 0.1 ml of undiluted D4 was administrated into the right eye of each of three New Zealand white rabbits. The eyes were rinsed with lukewarm water 24 hours after instillation, and were then scored for irritation at 1, 24, 48 and 72 hours following test substance administration. D4 was determined to not be irritating to eyes under the conditions of this study. Supporting studies confirm the conclusion that D4 is not irritating to the eyes.



Justification for classification or non-classification

Based on the available in vivo skin and eye irritation data, D4 does not require classification for skin and eye irritation according to Regulation (EC) No. 1272/2008.