Registration Dossier

Administrative data

Description of key information

Skin irritation: irritating (similar to OECD 404, GLP, Read-across, WoE, rel. 2)
Eye irritation: not irritating (similar to OECD 405, read-across, K, rel. 2)
Respiratory irritation: no data available

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From July 09 to 16, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to standard guideline. No details on test animals and environmental conditions. The supporting substance is considered adequate for read-across purpose (see Iuclid section 13 for justification).
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
other: Section 1500.42 - Hazardous Substances and Articles, Administration and Enforcement Regulations, Federal Register, Vol. 38. No. 187, p. 27019, 27 September 1973.
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: Healthy young adult albino rabbits were used.

IN-LIFE DATES: From: July 09, 1979 To: July 16, 1979
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Eyes of the animals were not rinsed.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: According to “Illustrated guide for grading eye irritation by hazardous substances”.

TOOL USED TO ASSESS SCORE: No data
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48 and 72 h
Score:
0.39
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritant / corrosive response data:
- Animals showed conjunctival reactions (redness, chemosis and discharge) which were reversible within 5 days.
Other effects:
None

Table 7.3.2/1: Mean eye irritation response data of 6 animals at each observation time

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

24 h

0

0

0

0.83

0.67

1

48 h

0

0

0

0.33

0.17

0.33

72 h

0

0

0

0

0.17

0.33

Mean

0

0

0

0.39

0.33

0.55

Reversibility

-

-

-

Completely

reversible

Completely reversible

Completely reversible

Average time for reversion

-

-

-

3 days

5 days

5 days

Table 7.3.2/2: Eye irritation response data for each animal at each observation time

Score at time

point

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

24 h (Day 1)

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 2 / 1 / 0 / 0 / 1

1 / 1 / 1 / 0 / 0 / 1

1 / 3 / 2 / 0 / 0 / 0

48 h (Day 2)

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 2 / 0 / 0 / 0 / 0

0 / 1 / 0 / 0 / 0 / 0

0 / 2 / 0 / 0 / 0 / 0

72 h (Day 3)

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 1 / 0 / 0 / 0 / 0

0 / 2 / 0 / 0 / 0 / 0

Day 5

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

Day 7

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

Average 24, 48 and 72 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0.33 / 1.33 / 0.33 / 0 / 0 / 0.33

0.33 / 1 / 0.33 / 0 / 0 / 0.33 

0.33 / 2.33 / 0.67 / 0 / 0 / 0

Reversibility

 -

 -

-

Completely

reversible

Completely reversible

Completely reversible

Average time (unit) for reversion

-

-

-

3 days

5 days

5 days

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test material induced mild irritation being reversible within 5 days. Therefore, the test material is not classified as irritant to the eyes.
Executive summary:

In an eye irritation study, 0.1 g of undiluted test material was instilled into the right eye of 6 albino rabbits while the left eye remained untreated and served as control. The eyes were not rinsed after the instillation of test material. Animals were observed at 24, 48 and 72 h after instillation of test material into eyes and then on Days 5 and 7. The reactions in the conjunctivae (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the “Illustrated guide for grading eye irritation by hazardous substances”.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.39 for redness, 0.33 for chemosis, 0.0 for iris lesions and 0.0 for corneal opacity. The observed conjunctival reactions were fully reversible within 5 days.

Under the test conditions, the test material is not classified as irritating to the eyes according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Although some details on test animals and experimental conditions were missing, this study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

The supporting substance is considered adequate for read-across purpose (see Iuclid section 13 for justification).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No studies were available on the substance itself regarding skin and eye irritation, therefore a read-across approach was used. The supporting substances are considered adequate for read-across purposes (see Iuclid section 13 for additional justification).

Skin irritation / corrosion:

Two studies were identified on the analogue, (3E)-3-methyl-4-(2,6,6-trimethyl-2 -cyclohexen-1-yl)-3-buten-2-one (Toxicol, 1992, rel. 2).

Both studies were performed similarly to the OECD Guideline No. 405 and in compliance with GLP but observation period was 7 days only, with non-reversible effects at the end of the observation period.

0.5 mL of test material was applied on the clipped skin of the flank area of 3 female New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 and 168 h after removal of the patches.

In the first study (Toxicol, 1984), o ne hour after dosing, very slight to well defined erythema and slight oedema were observed. At 24 h observation, well defined erythema and slight to moderate oedema were observed. Very slight to slight oedematous response was observed at 48 h after dosing. Moderate oedema was again observed in one rabbit 72 h after dosing, other irritant reactions remaining unchanged. The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 2.0 / 2.0 for erythema and 1.3 / 2.7 / 2.0 for oedema. At 168 h observation, very slight to well defined erythema and oedema were observed; animals exhibited desquamation from the surface of the treated skin. Reversibility was not observed in any of the treated rabbits.

In the second study (Toxicol, 1985), one hour after dosing, very slight to well defined erythema and very slight to moderate oedema were observed. 24 h after dosing, some changes to the intensity of oedematous reaction ware apparent; very slight to severe oedema was observed. 48 h after dosing, very slight to well defined erythema and slight to moderate oedema were observed. The moderate response described had declined slightly by the seventy two hour observation when well defined erythema and slight oedema were observed together with desquamation from the skin surface. The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.3 / 2.3 / 1.7 / 1.0 for erythema and 0.3 / 3.0 / 2.3 / 0.3 for oedema. At 168 h observation, the irritant response was generally maintained and desquamation from the treated skin surface was noted in three of the four animals.

Based on the scores, on the inflammation persisting at the end of the observation period and on the presence of desquamation, the substance requires classification for skin irritation.

Eye irritation:

A key study was identified on the analogue, (2E)-1-(2,6,6-trimethyl-2-cyclohexen-1-yl)-2-buten-1-one (Biosearch, 1979). In this eye irritation study performed similarly to the OECD Guideline No. 405, undiluted test material was instilled into the eye of 6 rabbits. The eyes were not rinsed after instillation of the test item. Animals were observed at 24, 48 and 72 h after instillation of test material into eyes and then on Days 5 and 7.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.39 for redness, 0.33 for chemosis, 0.0 for iris lesions and 0.0 for corneal opacity. The observed conjunctival reactions were fully reversible within 5 days.

The substance does not require classification for eye irritation.



Justification for selection of skin irritation / corrosion endpoint:
No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purposes as data relates to an isomer of the registered substance (see Iuclid section 13 for additional justification).
A weight -of-evidence using two reliable studies (Klimisch score=2) was used.

Justification for selection of eye irritation endpoint:
No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purposes (see Iuclid section 13 for additional justification).
The key study is GLP-compliant and of good quality (Klimisch score=2).

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP6.

Self-classification:

Based on the available information on the analogue, the registered substance should be classified as Skin irr. Category 2 (H315: Causes skin irritation) according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

No additional self-classification is proposed regarding eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

No information was available regarding respiratory irritation.