Registration Dossier

Administrative data

Description of key information

Lyral is not irritating to skin and eyes and is not expected to be a respiratory irritant either. 

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant OECD TG 404 study
Qualifier:
according to
Guideline:
other: skin irritation test described in the methods for the determination of toxicity in Annex V of EEC Directive 79/831
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: A. Smith, 7 Kydcomb Road, Warlingham, Surrey
- Housing: individually in anodised aluminium cages with grid floors and no bedding material
- Diet: commercially available pelleted rabbit diet (product ref. 680, Dalgety-Spillers Limited), ad libitum
- Water Mains tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 42-65
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
4 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm2
- % coverage: 100%
- Type of wrap if used: a length of "Elastoplast" elastic adhesive bandage 10 cm wide

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema formation:
0: no erythema
1: very slight erythema (barely perceptible)
2: well-defined erythema
3: moderate to severe erythema
4: severe erythema (beet redness) to slight eschar formation (injuries in depth)

Edema formation:
0: no edema
1: very slight edema (barely perceptible)
2: slight edema (edges of area well defined by definite raising)
3: moderate edema (raised approximately 1 mm)
4: severe edema (raised more than 1 mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 + 48 + 72 hr
Score:
1.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days in 2 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 + 48 + 72 hr
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Very slight erythema was observed in 2 animals 1 hour after dosing. The incidence of irritant reaction increased and 23 hours later very slight erythema of the treated skin was observed in three rabbits and well defined erythema and very slight edema were apparent in the remaining rabbit of the group. Slight changes in the severity or incidence of response occurred during the study and seven days after dosing very slight erythema of the skin remained in two rabbits, one of these exhibiting slight desquamation from the surface of the treated skin.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Lyral is not irritating to rabbit skin.
Executive summary:

Skin irritating properties of Lyral were studied in a GLP-compliant study with rabbits, performed according to the protocol described in the methods for the determination of toxicity in Annex V of EEC Directive 79/831. 0.5 mL of undiluted test substance was applied for 4 hours under semi-occlusive conditions to an area of 2.5 cm2 in 4 female rabbits. After 4 hours, the test substance was removed by gentle swabbing with cotton wool soaked in warm water, and animals were observed for 168 hours. The mean erythema and edema scores over 24, 48 and 72 hours were 1.2 and 0.2. In all cases, edema was fully reversible within 72 hours, while slight erythema (score 1) was still observed at the end of the 7 days observation period in 2 animals. Based on the results, Lyral was concluded to be non-irritating to rabbit skin.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predates GLP, but similar to OECD 405.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomas R. Hanna, Nashanic Station, N. J., USA
- Age at study initiation: adult
- Weight at study initiation: 2.5-3.1 kg
- Housing: singly under standard laboratory conditions. No extraneous material was used in cages.
- Diet: 100 g of Purina Rabbit Chow supplemented by whole oats daily
- Water: ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as a concurrent control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
A single instillation
Observation period (in vivo):
24, 48, 72 hr, 4, 7 and 10 days after dosing
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: not performed

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 + 48 + 72 hr
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hr
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 + 48 + 72 hr
Score:
0.1
Max. score:
2
Reversibility:
fully reversible within: 48 hr
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 + 48 + 72 hr
Score:
1.1
Max. score:
3
Reversibility:
fully reversible within: 72 hr
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 + 48 + 72 hr
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hr
Irritant / corrosive response data:
All of the animals had slight opacity over approximately 50% of the cornea 24 hours after dosing, which had cleared by 48 hours. At 24 hours the opaque areas retained dye. Conjunctival redness, observed in all animals 24 hours after dosing, had subsided by 72 hours, when all scores were 0. At Day 4 and Day 7 all scores were 0, and the eyes did not retain fluorescein dye.

The primary ocular irritation score was 19.7 at 24 hours, 2.3 at 48 hours and 0 at 72 hours, day 4 and day 7.
Other effects:
All animals remained healthy and showed normal behavior throughout the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Lyral is not irritating to rabbit eyes.
Executive summary:

Eye irritating properties of Lyral were studied in a pre-GLP study with rabbits, conducted according to a protocol similar to OECD Guideline 405. A single instillation of 0.1 mL undiluted test substance into the eyes of 6 rabbits resulted in mean scores of 0.3, 0.1, 1.1 and 0.3 for cornea, iris, conjunctiva and chemosis, respectively, over 24, 48 ad 72 hours. All effects were fully reversible within 72 hours. Based on these results, Lyral was concluded to be non-irritating to rabbit eyes.

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

Respiratory irritation

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

Additional information

Skin irritating properties of Lyral were studied in two GLP-compliant studies with rabbits (Toxicol Laboratories Limited, 1985 and 1984), performed according to the protocol described in the methods for the determination of toxicity in Annex V of EEC Directive 79/831 (similar to OECD 404). 0.5 mL of undiluted test substance was applied for 4 hours under semi-occlusive conditions to an area of 2.5 cm2 in 4 (1985) or 3 (1984) female rabbits. After 4 hours, the test substance was removed by gentle swabbing with cotton wool soaked in warm water, and animals were observed for 168 hours. The mean erythema and edema scores over 24, 48 and 72 hours were 1.2 and 0.2 (key study of 1985) and 1.4 and 0.3 (supporting study of 1984). In all cases, edema was fully reversible within 72 hours, while slight erythema (score 1) was still observed at the end of the 7 days observation period in 2 (1985) or 1 (1984) animals. Despite the fact that the irritation was not fully reversible at the end of the study period the effects were decreasing and minor and therefore Lyral was concluded to be non-irritating to rabbit skin. The study from 1985 is selected as key study with the study from 1984 supporting the results.

Eye irritating properties of Lyral were studied in a pre-GLP study with rabbits, conducted according to a protocol similar to OECD Guideline 405 (Cosmopolitan Safety Evaluation Inc., 1980). A single instillation of 0.1 mL undiluted test substance into the eyes of 6 rabbits resulted in mean scores of 0.3, 0.1, 1.1 and 0.3 for cornea, iris, conjunctiva and chemosis, respectively, over 24, 48 and 72 hours. All effects were fully reversible within 72 hours. Based on these results, Lyral was concluded to be non-irritating to rabbit eyes.

Respiratory irritation:  For assessing respiratory irritation mostly human data are used because no suitable in vitro or in vivo tests are available that can identify respiratory irritation (REACH guidance R.7.2.3). However, there are no human data such as indicated in R7.2.3 the ECHA guidance that indicate respiratory reactions of the substance e.g. from consumer experience or occupational exposure. In experimental tests Lyral is not corrosive or irritating for the skin or eye, which minimizes the respiratory irritation hazard (REACH guidance: 7.2.1.2). Furthermore Lyral has a low volatility of 0.0055 Pa and will limitedly vapourise as such and from mixtures. Therefore no C&L is needed for the respiratory irritation.


Justification for selection of skin irritation / corrosion endpoint:
Skin irritation needs to be assessed according to the REACH regulation. Two studies are available similar to OECD TG 404 with similar results. The most recent has been selected.

Justification for selection of eye irritation endpoint:
Eye irritation needs to be assessed according to the REACH regulation. The one study available is performed according to OECD TG 405.

Justification for classification or non-classification

Based on the results of comparable to guideline studies, classification of the substance as irritating to skin and eyes is not warranted in accordance with EU Directive 67/548 (DSD) and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Since Lyral is not corrosive or irritating to the skin and eye and because of its low volatility, classification is not needed for respiratory irritation.