Registration Dossier

Administrative data

Description of key information

Skin irritation (Rat-Wistar, GLP, non-audited draft, similar to OECD TG404): not irritant or corrosive to skin
[Schering AG, Report No. X024, 1995-07-18; combined acute dermal toxicity and local tolerance study]
Eye irritation (Rabbit-NZW, GLP, non-audited draft, equivalent to OECD TG405): not irritant or corrosive to the eye
[Schering AG, Report No. X031, 1995-07-21]

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:
23. Feb to 22. March 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
, test-species rat, 6 animals used, application volume 0.3 mL, exposure period 24 hours
Principles of method if other than guideline:
Combined acute dermal toxicity and local irritation study; single dermal application of test substance (application volume 0.3 mL) to 3 male and 3 female rats; semi-occlusive conditions; exposure for 24 hours; values for reddening/scab formation and swelling obtained immediately after removal of the substance and at time-point 24, 48 and 72 h.
GLP compliance:
yes
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: HAN: WIST (SPF)
- Source: Schering AG
- Age at study initiation: not reported
- Weight at study initiation: males 106-112 g, females 101-111 g
- Housing: singly in conventional housing conditions
- Diet and water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 54-62
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
physiological saline
Controls:
not specified
Amount / concentration applied:
212-224 mg/male rat; 208-222 mg/female rat
The test substance was formulated with 0.9 mL physiological saline solution and then applied as a paste onto the skin.
Duration of treatment / exposure:
24 h
Observation period:
14 days
Number of animals:
6 (3/sex)
Details on study design:
DETAILS ON STUDY DESIGN:
- Frequency of observations and weighing: Animals were observed for clinical signs several times on day 1 and at least once daily throughout the rest of the study. Body weights were determined at study start (day 1), on day 7 and at termination of the study (day 14).

TEST SITE
- Type of wrap if used: no data

SCORING SYSTEM:
- Draize, in: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Topeka, Kansas; Second Printing 1965, 46-59.
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Other effects:
none; compare data on acute dermal toxicity in same study report (Combined acute toxicity and local tolerance study)
Conclusions:
No classification required for skin irritation/corrosion according to Directive 67/548/EEC and Regulation (EC) 1272/2008.
Executive summary:

A combined acute dermal toxicity and local tolerance test on 6 rats is available for the substance. In this study a 24 -hour dermal exposure to a volume of 0.3 mL under semi-occlusive conditions did not lead to any skin effects at all. Time-points for read-out were directly after the end of exposure, and after 24, 48, and 72 hours. The scoring system was according to Draize (in: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Topeka, Kansas; Second Printing 1965, 46-59).

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:
March 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: females
- Source: Schriever
- Age at study initiation: not reported
- Weight at study initiation: 3.4-4.4 kg
- Housing: singly in conventional housing conditions (metal cage)
- Diet and water: ad libitum
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 48-56
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye remained untreated and served as control
Amount / concentration applied:
0.1 mL, corresponding to 54.0-64.3 mg substance
Duration of treatment / exposure:
0.1 mL substance was applied into the conjunctival sac of the right eye; no rinsing of the eyes reported.
Observation period (in vivo):
Examinations were terminated after 4 days, since no changes at all were observed during this period.
Number of animals or in vitro replicates:
4 (females)
Details on study design:
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. Conjunctivae, eyelids, cornea and iris were evaluated before application, 0.5, 1 and 2 hours thereafter and then once daily until termination of the study on day 4.

SCORING SYSTEM:
According to "Illustrated Guide for Grading Eye Irritation by Hazardous Substances", US Department of Health, Education and Welfare, Food and Drug Administration, Washington DC 20204, USA.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
/reddening
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
The single application of the substance into the conjunctival sac of the rabbit eye led to slight to moderate transient irritation (vessel injection and secreation in 2/4 animals) solely on the day of application. From day 2 onwards all animals were without findings.
Other effects:
not reported
Conclusions:
No classification required for eye irritation/corrosion according to Directive 67/548/EEC and Regulation (EC) 1272/2008.
Executive summary:

0.1 mL test substance was applied into the conjunctival sac of 4 rabbits. Assessment of eye irritation was made on the application day and after 24, 48, and 72 hours according to "Illustrated Guide for Grading Eye Irritation by Hazardous Substances", US Department of Health, Education and Welfare, Food and Drug Administration, Washington DC 20204, USA. Solely on application day the substance provoked slight to moderate transient irritation (vessel injection and secreation) in 2/4 animals. From Day 2 onwards all animals were without findings.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For assessing skin irritation a combined acute dermal toxicity and local tolerance test on rats (3 males, 3 females) is available for the substance. In this study a 24 -hour dermal exposure to a volume of 0.3 mL under semi-occlusive conditions, did not lead to any skin effects at all. Time-points for read-out were directly after the end of exposure, and after 24, 48, and 72 hours. The scoring system was according to Draize (in: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Topeka, Kansas; Second Printing 1965, 46-59). Although the testing protocol deviated from the protocol of OECD TG 404 (rat instead of preferred species rabbit, dose 0.3 mL (paste) instead 0.5 mL, 6 instead of 3 animals, 24 hours exposure instead of 4 hours) it adequately assessed the irritant properties of the substance, since the exposure time was 6 times the usual exposure time and 6 instead of 3 animals were used.

[Schering AG, Report No. X024, 1995-07-18; combined acute dermal toxicity and local tolerance study]

For investigating eye irritation properties 0.1 mL test substance was applied into the conjunctival sac of 4 rabbits. Assessment of eye irritation was made on the application day and after 24, 48, and 72 hours according to "Illustrated Guide for Grading Eye Irritation by Hazardous Substances", US Department of Health, Education and Welfare, Food and Drug Administration, Washington DC 20204, USA. Solely on application day the substance provoked slight to moderate transient irritations (vessel injection and secreation) in 2/4 animals. From Day 2 onwards all animals were without findings.

[Schering AG, Report No. X031, 1995-07-21]

No study investigating a respiratory irritant potential of the substance is available. But as no irritant potential was seen in the above specified in vivo irritation/corrosion studies on skin and eye (all scores zero at 24, 48, and 72 h), it is unlikely that the substance would show a respiratory irritant property.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Justification for classification or non-classification

No classification required for skin, eye or respiratory irritation/corrosion according to Directive 67/548/EEC or according to Regulation (EC) 1272/2008.