Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation: The undiluted test substance was reported to be irritating to skin in the key study with rabbits, an effect also seen in further reliable animal studies. Corrosive effects were not evident.
Eye irritation: The undiluted test substance was slightly to moderately irritating to the eye in reliable rabbit studies, but effects were still present at the end of the observation time.
No human data are available with respect to skin or eye irritation.
Respiratory irritation: The RD50 (concentration producing a 50% decrease in respiratory frequency) in mice was 420 mg/m3.

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:
1986-06-24 to 1986-07-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was performed according to guideline OECD 404.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Small White Russian, Chbb-SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Weight at study initiation: 1.97-2.07 kg
- Housing: individual in cages
- Diet: K4 Alleindiät für Kaninchen, Ssniff Spezialfutter, Soest, Germany, ad libitum
- Water: ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15-fold
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
Examination of effects was performed 1, 24, 48 and 72 h, 6, 8, 10 and 14 days after end of exposure.
Number of animals:
3 males
Details on study design:
Areas of about 10 x 10 cm were shaved at dorsal and lateral patrs of the body 24 h prior to exposure.
0.5 ml were applicated to areas of about 6 cm2, occluded by a plaster and polyethelyene foil.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1-72 h
Score:
5.67
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: individual scores (24-48-72 h): 3.0, 3.0, 3.0, calculated from the result data
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: individual scores (24-48-72 h): 2.67, 3.67, 2.67, calculated from the result data
Irritant / corrosive response data:
There was erythema as well as edema formation , accompanied by yellow-brown discolouration and hardening of the application sites. Eschars persisted until day 14, and began to peel off from day 10 on (details see below).

  Animal No. Er, 1 h  Ed, 1h   Er, 24 h   Ed, 24 h   Er, 48 h   Ed, 48 h   Er, 72 h   Ed, 72 h 

Er: erythema score, Ed: edema score

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the test substance was irritating to the skin of rabbits.
Executive summary:

Rabbits were exposed for 4 h under occlusive conditions to 0.5 mL of the test item in a skin irritation test according to OECD TG 404 (Hüls AG, 1986). At the end of the exposure period and at the 24 -48 -72 hour reading there was erythema as well as edema formation, accompanied by yellow-brown discolouration and hardening of the application sites. Mean 24 -48 -73 h erythema and edema scores were 3 and 3, respectively. Eschars persisted until day 14, and began to peel off from day 10 on.

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
Study period:
1986-06-24 to 1986-07-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was performed according to OECD guideline 405
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Small White Russian, Chbb-SPF
Details on test animals or tissues and environmental conditions:
- Source: Thomae, Biberach, Germany
- Weight at study initiation: 1.97-2.1 kg
- Housing: individual in cages
- Diet: K4 Alleindiät für Kaninchen, Ssniff Spezialfutter, Soest, Germany, ad libitum
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15-fold
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
72 h
Observation period (in vivo):
1, 24, 48 and 72 h as well as 6, 8, 10, 13, 17 and 21 days post application
Number of animals or in vitro replicates:
3 males
Details on study design:
0.1 ml of the test substance was applied into the conjunctival sac of one eye of each animal, the other eye served as control. The exposed eye was treated with fluorescein solution to detect cornea damage and afterwards rinsed with warm physiological saline.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 h - 21 days
Score:
41.84
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.78
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: individual scores (24-48-72 h): 2.0, 1.67, 1.67, calculated from the data in the attached document
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: individual scores (24-48-72 h): 1.0, 1.0, 1.0, calculated from the data in the attached document
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: individual scores (24-48-72 h): 3.0, 3.0, 3.0, calculated from the data in the attached document
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: individual scores (24-48-72 h): 1.0, 1.0, 1.0, calculated from the data in the attached document
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test substance was irritating to the eye. As lesions were still persisting at the end of the observation period, the results have to be considered as "severely irritating to the eye".
Executive summary:

Effects on eyes have been assessed in a test according to OECD TG 405. The application of undiluted test substance to the eyes of rabbits produced an eye irritation to be considered as severe (effects still present at the end of the observation time; overall irritation score: 41.48/110, cornea score:1.78/4, iris score: 1/2, conjunctivae score: 3.0/3, chemosis score: 1.0/4) (Hüls AG, 1986).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: The key study reports an erythema score of 3.0 and an edema score of 3.0 (Hüls, 1986, RL1). A further reliable study documents lower scores of 1.0 and 0, respectively, with skin effects like scaly, dry, and rough skin, which were still present at the end of the 14 -day observation period (Hoechst, 1985, RL1). Both studies were performed according to guidelines EU B4 and OECD 404. A secondary report of an unavailable study reports slight skin irritation with scores < 2.0 (Exxon, undated). An additional study with 24 hour exposure time revealed skin irritating effects (erythema score 2.9; edema score 1.9, not reversible within 8 days). One of six treated animals showed a slight, superficial necrosis which did not extent to deeper skin layers, i.e. is not relevant with respect to classification as skin corrosive.

Eye irritation: The key study reports a moderate irritating effect to the eye. Lesions were still present at the end of the observation time therefore the eye irritation has to be considered as severe (Hüls, 1986, RL1: cornea score: 1.78; iris score: 1.0; conjunctiva reddening score: 3.0; chemosis score: 1.0). A similar result (slight but irreversible eye effects) was also observed in a further study by BASF AG (1980). A further reliable study documents lower scores (Hoechst, 1985, RL1: 0; 0.8; 2.1 and 1.7, respectively). Studies of restricted reliability (Hoechst, 1970; Exxon undated) report moderate and slight irritating properties, respectively.

Respiratory irritation: The RD50 (concentration producing a 50% decrease in respiratory frequency) in mice was 420 mg/m3. According to the authors, the effect was mainly based on pulmonary irritation (Detwiler-Okabayashi and Schaper, 1996). The study per se is reliable, but the result is of unclear relevance with respect to the classification of endpoint respiratory irritation, as no supportive data (e.g. histological examinations) are available.

Justification for classification or non-classification

Based on the results of the key study for skin irritation a classification as skin irritant (Category 2) is recommended according to Regulation (EC) No 1272/2008.

Based on the results of the key study for eye irritation, a classification for irreversible effects on the eye (Category 1) is recommended according to Regulation (EC) No 1272/2008.

Reliable and relevant data for the endpoint respiratory irritation are not available.

Categories Display