Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating , weight of evidence approach using OECD 404 (Rel.3) and OECD 439 (read-across, Rel.2)
Eye irritation: not irritating (US FHSA method, K, Rel. 2)
Respiratory irritation: no data available

Key value for chemical safety assessment

Skin irritation / corrosion

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:
From August 6 to 13, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study comparable to OECD test guideline No. 405 with deviations not affecting the integrity of the result. Even if full reversibility was not achieved for conjunctival reactions within the observation period of 7 days, only minimal responses (score = 1) persisted at the end of the observation period. Complete reversibility would have probably occurred if the observation period was extended to 21 days, as required by the current OECD TG 405.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
other: Section 1500.42 - Federal Hazardous Substances Act Regulations - 16 CFR
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, USA
- Housing: Animals were housed individually in stainless steel cages with elevated wire mesh flooring.
- Diet: Wayne 15 % Rabbit Ration, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Animals were acclimated to the laboratory for an appropriate time prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature: 60-75 °F
- Humidity: 40-45 %
- Photoperiod: 12 h light/12 h dark

IN-LIFE DATES: From: August 6, 1984 To: August 13, 1984
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 mL
Duration of treatment / exposure:
- Test material was not washed from the eyes of animals.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: According to the 'Draize technique'

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:
1
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
- Animals showed conjunctival reactions (redness, chemosis and discharge) which were not fully reversible within 7 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

1

1

1

48 h

0

0

0

1

1.17

0.5

72 h

0

0

0

1

0.83

0.17

Mean

0

0

0

1

1

0.56

Reversibility

-

-

-

Not completely

reversible

Not Completely reversible

Not Completely reversible

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

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 1 / 1 / 1 /1 / 1

1 / 2 / 1 / 1 / 1 / 0

0 / 1 / 1 / 2 / 1 / 1

48 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 1 / 1 / 1 / 1 / 1

1 / 2 / 1 / 1 / 1 / 1

0 / 1 / 1 / 1 / 0 / 0

72 h

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 1 / 1 / 1 / 1 / 1

1 / 2 / 1 / 1 / 0 / 0

0 / 0 / 0 / 0 / 1 / 0

Day 4

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 1 / 1 / 1 / 1 / 1

1 / 2 / 0 / 0 / 0 / 0

0 / 0 / 0 / 1 / 0 / 0

Day 7

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

0 / 0 / 0 / 0 / 0 / 0

1 / 1 / 1 / 1 / 0 / 0

1 / 1 / 0 / 0 / 0 / 0

0 / 1 / 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

1 / 1 / 1 / 1 / 1 / 1

1 / 2 / 1 / 1 / 0.67 / 0.33

0 / 0.67 / 0.67 / 1 / 0.67 / 0.33

Reversibility

 -

-

-

Not completely

reversible

Not Completely reversible

Not Completely reversible

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test material induced slight to moderate irritations and even full reversibility was not achieved for conjunctival reactions, the observation period was only 7 days and a beginning of recovery was observed. Therefore the test material is not classified as irritant to the eyes.

Executive summary:
In an eye irritation study performed according to US-FHSA method, 0.1 mL of undiluted test material was instilled into the conjunctival sac of one eye of 6 New Zealand White rabbits while the remained untreated eye 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 4 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 Draize scale.   The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 1 for redness, 1 for chemosis and 0.0 for iris lesions and 0.0 for corneal opacity. Animals showed conjunctival reactions (redness, chemosis and discharge) which were not fully reversible within 7 days. Even if full reversibility was not achieved for conjunctival reactions within the observation period of 7 days, only minimal responses (score = 1) persisted at the end of the observation period. Complete reversibility would have probably occurred if the observation period was extended to 21 days, as required by the current OECD TG 405;   Under the test conditions, the test material is not classified as irritating to the eyes according to the Annex I of the Regulation EC No. 1272/2008 (CLP). This study is considered as acceptable and satisfies the requirement for acute eye irritation endpoint.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

A study was available on the substance itself but was not sufficiently robust to be the key study (Biosearch, 1984, Rel.3). Indeed, deviations from OECD Test Guideline No. 404 were noted: the exposure period was 24 hours instead of 4 hours, occlusive dressing was used instead of semi-occlusive dressing, and the animals were observed for 3 days instead of 14 days although complete reversibility was not achieved. This study was thus not sufficient on its own to conclude on the skin irritation potential. Therefore a weight of evidence approach using athe study on the substance and on a supporting substance was followed. The supporting substance is considered adequate for read-across purposes as the data relates to a mixture composed of the same isomers that the registered substance, but at different ratios (see Iuclid section 13 for additional justification).

A reliable study was identified on the supporting substance (Harlan, 2014, rel. 2). The skin irritation potential of the test material was evaluated using the EPISKINTMreconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours. This test was designed to be compatible with the Method B.46 of Commission Regulation (EC) No. 440/2008/EC and was performed in compliance with GLP. T

he quality criteria required for acceptance of results in the test were satisfied.The relative mean viability of the test item treated tissues was 63.7± 8.4 %, after the 15‑minute exposure period. With a tissue viability > 50%, the test material was not considered to be irritant to skin.

Taken together within a weight-of-evidence approach, data suggest that the substance should not be classified for skin irritation.

Eye irritation:

A key study was identified (Biosearch, 1984, Rel.2). In athis eye irritation study performed according to US-FHSA method, 0.1 mL of undiluted test material was instilled into the conjunctival sac of one eye of 6 New Zealand White rabbits while the remained untreated eye 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 4 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 Draize scale.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 1 for redness, 1 for chemosis and 0.0 for iris lesions and 0.0 for corneal opacity. Animals showed conjunctival reactions (redness, chemosis and discharge) which were not fully reversible within 7 days but the observation period was only 7 days and a beginning of recovery was observed.


Justification for selection of skin irritation / corrosion endpoint:
A study was available on the substance itself, but was of poor quality (Klimish score =3). Therefore a weight-of-evidence approach using data on a supporting substance was used. The supporting substance is considered adequate for read-across purposes as data relates to a mixture composed of the same isomers that the registered substance, but at different ratios (see Iuclid section 13 for additional justification).

Justification for selection of eye irritation endpoint:
Only one study available (US-FHSA, non-GLP, Klimish score=2)

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 data on the analogue, no additional self-classification is proposed for the registered substance regarding skin and eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

 

No data was available regarding respiratory irritation.