Registration Dossier

Administrative data

Description of key information

Skin: The test substance was irritating to rabbits' skin under test conditions chosen (BASF, 1980) and showed an irritating potential in an in vitro Epiderm SCT/SIT Test (according to OECD guideline and GLP, 2010).
Eye: The test substance causes severe eye damage under test conditions chosen.

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:
weight of evidence
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP and no guideline study.
Principles of method if other than guideline:
according to the regulation of the Department of Transportation, Fed.Reg., § 173.1200
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
Mean body weight: ca. 2.8 kg
The animals were offered Ssniff K, standard diet for rabbits and guinea pigs, supplied by INTERMAST GMBH, Soest, FRG, and water ad libitum.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
other: untreated skin of the same animal
Amount / concentration applied:
0.5 g of an 80% aqueous test substance preparation
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
4
Details on study design:
The hair was removed from the dorsal and lateral parts of the trunk using electric clippers about 15 to 24 hours before application. Only animals with healthy and intact skin were used for the study.
The clipped dorsal skin of the rabbits was exposed to a test patch (about 2 x 2 cm) containing the test substance for 4 hours. The test patch was covered with a rubberised linen cloth that was secured in place by adhesive tape. After 4 hours the bandage was removed and the treated skin areas were washed with Lutrol or a mixture of water and Lutrol (1 : 1) and then dried with cellulose. The first findings were recorded after the bandage had been removed and then each working day. During the application the animals were restrained and did not receive any food.
Examinations:
a) Local irritation or corrosion
b) Signs of systemic toxicity
c) Necropsy of sacrificed animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h, 48 h
Score:
2.625
Max. score:
4
Reversibility:
other: not fully reversible within 8 days in 3 out of 4 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h, 48 h
Score:
1.875
Max. score:
4
Reversibility:
other: not fully reversible within 8 days in 1 out of 4 animals
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: parchment-like necrosis
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: parchment-like necrosis
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: spotty-necrotic skin lesion
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: within 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 48 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: parchment-like necrosis
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: parchment-like necrosis
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: spotty-necrotic skin lesion
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
After the 4-hour test substance application, initially distinct erythema and edema were observed. In the course of 8-day observation period, 2 of 4 animals showed parchment-like necrosis as a result of an irreversible skin damage. One animal showed a spotty-necrotic skin lesion. The skin findings were macroscopically confirmed by a pathologist. Parchment-like necosis are considered to present strong irritation (not corrosion).
Interpretation of results:
Category 2 (irritant)
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information given
Principles of method if other than guideline:
according to BASF-internal standard
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
50 mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Details on study design:
Single instillation into the conjunctival sac of the right eyelid; the test substance was not washed out.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: corroded mucosa
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h
Score:
1.5
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: corroded mucosa
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: corroded mucosa
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Other effects:
Effects were not fully reversible after 8 days and the animals had developed iritis.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

Weight oif Evidence:

In vitro:
The potential of the test substance to cause dermal corrosion/irritation was assessed by a single topical application of 25 µL bulk volume (about 18 mg) of the test item to a reconstructed three dimensional human epidermis model (EpiDerm). For the corrosion test two EpiDerm tissue samples were incubated with the test substance for 3 minutes and 1 hour, respectively. The irritation test was performed with three EpiDerm tissue samples, which were incubated with the test substance for 1 hour followed by a 42 -hour post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as suitable endpoint. The formazan production of the test-substance treated epidermal tissue is compared to that of the negative control tissues. The quotient of the values indicates the relative tissue viability.
In the EpiDerm skin corrosivity/irritation test the test substance was not able to reduce MTT directly.
Corrosion test:The mean viability of the test-substance treated tissues determined after an exposure period of 3 minutes was 100%, and it was 17% after an exposure period of 1 hour.
Irritation test:The mean viability of the test-substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 11%.
Bases in the observed results it was concluded, that the test substance shows a skin irritation potential in the EpiDermTM skin corrosion/irritation test under the test conditions chosen.


In vivo:
In a primary dermal irritation study (BASF, 1980) according to the Department of Transportation, Fed. Reg., § 173.1200 (1980), four male Vienna White rabbits were dermally exposed to 0.5 g of an 80% aqueous test substance preparation. The test substance was applied in a single dose (2 x 2 cm, occlusive) to the clipped skin of the back of an experimental animal for 4 hours (test item was washed off). Untreated skin areas served as the control. The degree of irritation was observed after 4 hours, 1 day, 2 days and 8 days. For the evaluation of the results, the scheme was converted to the OECD Draize schema. After the 4-hour test substance application, initially distinct erythema and edema were observed. The mean erythema score (24h/48h) was 2.625 and the mean edema score (24h/48h) was 1.875. In the course of 8-day observation period, 2 of 4 animals showed parchment-like necrosis as a result of an irreversible skin damage. One animal showed a spotty-necrotic skin lesion. Parchment-like necrosis present strong irritation (not corrosion).


In a primary dermal irritation study (BASF, 1967) according to BASF-internal standard, two Vienna White rabbits were dermally exposed to an 80% aqueous test substance preparation. The test substance was applied in a single dose (occlusive) to the clipped skin (back and ear) of an experimental animal for 20 hours (test item was not washed off). Untreated skin areas served as the control. The degree of irritation was scored at 1 min, 5 min, 15 min, 24 h and 8 days. For the evaluation of the results, the BASF scheme was converted to the OECD Draize schema. After the 20 hours application the mean erythema score was 2 and the edema score was 3 after 24 hours. After 8 day a severe necrosis was observed. Based on these results the test substance is considered as a skin irritant. However, as the exposure duration was 20 h and hence not according to current standards and considering that exposure for 4 h resulted in largely less effects and that an in vitro assay concluded the substance to be irritating (not corrosive), the result of this supporting study was not considered for classification purposes.


Eye irritation:
In a primary irritation study according to BASF-internal standard, 50 mg of the test substance without a vehicle was instilled into the conjunctival sac of the right eye of two Vienna White rabbits. The left eye served as the untreated control for each rabbit. The test substance was not washed out. animals then were observed at the following time points: 1h, 24 h and after 8 days. For the evaluation of the results, the BASF scheme was converted to the OECD Draize schema. The mean cornea score was 3, the mean chemosis score was 4 and the mean conjunctiva score was 1.5 after 24 hours. Effects were not fully reversible after 8 days and the animals had developed iritis. Based on these results, the test item causes severe eye damage.

Justification for classification or non-classification

The available studies are considered reliable and suitable for classification purposes under regulation 1272/2008. As a result the substance is considered to be classified and labelled as skin irritating cat. 2, H315 and causes severe eye damage cat. 1, H 318.