Registration Dossier

Administrative data

Description of key information

- Skin irritation / corrosion: not irritating in an acute dermal toxicity study (OECD 402, GLP, rel.1) and in humans.

- Eye irritation: not irritating (OECD 405, GLP, K, rel.1).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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:
06-10 July 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline 405 (1987) with minor deviations: no certificate of analysis of the test substance; age of animals at start of study not reported
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no certificate of analysis of the test substance; age of animals at start of study not reported; non-ocular local and systemic adverse effects not followed
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF albino rabbits of the stock Mol:Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Møllegaard Breeding and Research Centre A/S, Ejby, Denmark
- Weight at study initiation: 2.4-2.8 kg
- Housing: Animals were housed individually in PPO cages with perforated floor
- Diet: Pelleted complete rabbit diet "Altromin 2123" (Altromin, Lage, Germany), ad libitum
- Water: Domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 55 ± 15 %
- Air changes: 10/h
- Photoperiod: 12 h dark / 12 h light
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
4 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: After the first 24 h reading fluorescein was instilled. After rinsing with 20 mL 0.9% sodium chloride solution, the eyes were examined again using UV -light to detect possible corneal damage.

SCORING SYSTEM: Draize (1977) scoring system

TOOL USED TO ASSESS SCORE: Eyes of the animals were examined with a hand held inspection lamp fitted with white and UV -light and magnifying glass with 2 X magnifications. The examination was performed before and after instillation of fluorescein.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
4 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
4 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
4 animals
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
4 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
- One hour after application of the test article all animals showed some conjunctival vessels definitely injected.
- After 24, 48 and 72 h all animals were free of any signs of eye irritation.
Other effects:
No data

Table 7.3.2/1: Scores for ocular lesions

Rabbit no./ Body weight (kg)

Region of eye

Scores

1 h

24 h

48 h

72 h

Individual mean score

1466 / 2.4

Corneal opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae: Redness

1

0

0

0

0

Conjunctivae: Chemosis

0

0

0

0

0

1470 / 2.4

Corneal opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae: Redness

1

0

0

0

0

Conjunctivae: Chemosis

0

0

0

0

0

1474 / 2.8

Corneal opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae: Redness

1

0

0

0

0

Conjunctivae: Chemosis

0

0

0

0

0

1477 / 2.8

Corneal opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae: Redness

1

0

0

0

0

Conjunctivae: Chemosis

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, γ-Undecalactone is not classified as irritating to eyes according to Regulation (EC) No.1272-2008 (CLP) and to the GHS criteria.
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 4 female albino rabbits of the Mol:Russian strain were exposed to 0.1 mL of γ-Undecalactone in their left eye, while the right eye remained untreated and served as control. The eyelids were then gently held together for 1 second to avoid any loss of the test material. Eyes were examined 1 and 24 h after instillation of the test material. After the 24 h reading, fluorescein was instilled. After rinsing with 20 mL 0.9 % sodium chloride solution, the eyes were examined again using UV-light to detect possible corneal damage. Eyes were also examined 48 and 72 h after the treatment. Ocular reactions were graded according to the method of Draize (1977).

One hour after application of the test article all animals showed some conjunctival vessels definitely injected. After 24, 48 and 72 h all animals were free of any signs of eye irritation. The calculated mean scores for each ocular lesions for all animals within three scoring times (24, 48 and 72 h) were as follows: 0.00 for cornea score; 0.00 for iris score; 0.00 for conjunctivae score and 0.00 for chemosis score, respectively. In this study, γ-Undecalactone is not an eye irritant on rabbits.

Under the test conditions, γ-Undecalactone is not classified as irritating to eyes according to the Annex I of the Regulation (EC) N° 1272-2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirements for 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

In accordance with column 2 of REACH Annex VII & VIII (§8.1), the in vitro and/or in vivo skin irritation studies do not need to be conducted since the acute toxicity study by dermal route conducted on γ-Undecalactone does not indicate any skin irritation up to the limit dose of 2000 mg/kg bw. This waiving is supported by the absence of irritation in 50 adult male volunteers exposed to 0.05 g of γ-Undecalactone (35% in acetone) during 48 hours (see §"Exposure related observations in humans").

Eye irritation:

A key study was identified (Schreiter, 1999, rel.1). In this eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, rabbits were exposed to 0.1 mL of γ-Undecalactone in their left eye, while the right eye remained untreated and served as control. One hour after application of the test article all animals showed some conjunctival vessels definitely injected. After 24, 48 and 72 h all animals were free of any signs of eye irritation. The calculated mean scores for each ocular lesions for all animals within three scoring times (24, 48 and 72 h) were as follows: 0.00 for cornea score; 0.00 for iris score; 0.00 for conjunctivae score and 0.00 for chemosis score, respectively. In this study, γ-Undecalactone is not an eye irritant.

Justification for classification or non-classification

Harmonized classification:

γ-Undecalactone has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Based on the available data no additional self-classification is proposed regarding both skin and eye irritation according to Annex I of the Regulation (EC) No. 1272/2008 (CLP) and the GHS.