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Description of key information

The registered substance did not exert irritant effects on skin and eyes of rabbits in vivo.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03 MAY 1976 to 6 MAY 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: testing regime differs to some extent from today's standard methods, but conclusion on C&L is possible
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973)
Deviations:
not specified
GLP compliance:
yes
Remarks:
GLP was not compulsory at the time the study was conducted
Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: individually
- Weight at study initiation: 1.5-2.0 kg
- Diet: mixed feed ERKA 8300 (Robert Koch, Hamm), ad libitum
- Water: tap water, ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: two areas on one flank: one clipped one scarified respectively
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
24 h
Observation period:
48 h after end of exposure
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm gauze patch
- Type of wrap if used: PVC foil, elastic bandage

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

SCORING SYSTEM: described in § 1500.41 in Fed. Reg. 38, No. 187, 27.09.1973, p. 27019, in accordance with OECD TG 404.
Scores were assessed 24, 48 and 72 h after start of exposure, which lasted for 24 h. For classification, the readings are stated here as immediately, 24 and 48 h after end of exposure.
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #4 and #5 each
Time point:
other: mean of 24 and 48 h after end of treatment
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since no effects
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean of 24 and 48 h after end of treatment
Score:
0.5
Max. score:
4
Reversibility:
not fully reversible within: 48 h (end of observation)
Remarks on result:
no indication of irritation
Remarks:
The test item is intensly red colored,. remaining traces might appear as "erythema"
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: mean of 24 and 48 h after end of treatment
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 48 h (end of observation)
Remarks on result:
no indication of irritation
Remarks:
The test item is intensly red colored,. remaining traces might appear as "erythema"
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 48 h after end of treatment
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since no effect
Irritant / corrosive response data:
The Erythema score could not be determined immediately after end of exposure due to pigment overlay. Animal #3 had an erythema score of 0 and 1 (24 and 48 h), Animal #6 had 1 and 1 in the 24 and 48 h reading. No erythema was observed in the other animals. No edema were observed at any time point.
Readings on the scarified skin showed comparable results.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study the observation period was not long enough to check whether the observed effects are fully reversible. A longer observation period would have been preferable, because 2/6 animals showed an erythema score of 1 in the 48 h reading. But since severity was weak and incidence was low it can plausibly be assumed that the effects observed would have been completely reversible within a longer observation time.

The applied testing regime differs from today's standard methods in so far as the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin).

Based on that, it can reasonably be concluded that the test item is not a skin irritant.
Executive summary:

The test material was tested for skin irritancy according to FDA guidelines. Both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance for 24 h under occlusive conditions and the skin responses were watched for 48 h after end of exposure. In animals with intact skin no edema were seen at any time point (score 0), slight erythema were seen in one animal after 24 h (score 1) and in two animals after 48 h. No erythema evaluation was possible immediately after end of exposure due to coloration of the skin. Effects on scarified skin were comparable to those observed on intact skin.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 03 May 1976 to 06 MAY 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973)
Deviations:
no
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted)
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: individually
- Weight at study initiation: 1.5-2.0 kg
- Diet: mixed feed ERKA 8300 (Robert Koch, Hamm), ad libitum
- Water: tap water, ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological saline
- Time after start of exposure: 24 h

SCORING SYSTEM: basically in accordance with OECD TG 405.
Scores were read 1, 7, 24, 48 and 72 h after test substance application.

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein at 48 and 72 h reading
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since no effect
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not relevant since no effects
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
The test item is intensly red colored,. remaining traces might appear as "erythema"
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #1, #2, #4, #5, #6 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility not relevant since no effects
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since no effects
Irritant / corrosive response data:
Animals #3 showed redness of the conjunctivae 7 h after application, this effect persisted up to 48 h. Animal #2 and #6 showed discharge after 1 h (score 1). This effect was completely reversible within 7 h. No other effects could be observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was not irritating to eyes under test conditions which are basically in accordance with todays standard methods regarding dosing, exposureduration, scoring system and reading time points. One animal showed a conjunctiva redness score of 1 in the 7 h and 24 h reading. This effect was completely reversible within 48 h. Two animals showed a discharge score of 1 in the 1 h reading. No other effects were observed.
Therefore, it is concluded that the submission substance is not irritating to eyes.
Executive summary:

Test material was subject to a test of eye irritancy according to FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973). 100 mg of substance were applied to one eye of six animals. The eyes were washed 24 h after application and eye responses were noted for 72 h. One animal showed a conjunctiva redness score of 1 in the 7 h and 24 h reading. This effect was completely reversible within 48 h. Two animals showed a discharge score of 1 in the 1 h reading. No other effects were observed. Therefore, it is concluded that the submission substance is not irritating to eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

No classification


The registered substance proved not irritant on skin and eyes in vivo.