Registration Dossier

Administrative data

Description of key information

Two guideline in vivo skin irritation studies (OECD404) have been performed with technical grade and purified decan-1,2-diol respectively and very similar results were observed in the two studies in New Zealand White rabbits which resulted in a non-classification for skin irritation under CLP Regulation (EC) No. 1272/2008.
A regulatory in vivo eye irritation study in a rabbit also indicated irreversible damage and a Category 1 classification which was supported by positive results in a non-Regulatory HET-CAM test.

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: Performed in accordance with published test guidelines (OECD404 and EU B.4) and in accordance with GLP.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.0- 3.5 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): Free access to food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water (e.g. ad libitum): Free access to mains drinking water a
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
- Concentration (if solution): in 0.5mL of water (i.e. 1g/mL)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): 1g/mL
Duration of treatment / exposure:
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
Observation period:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: Dorsal flank area
- Type of wrap if used: elasticated corset

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

SCORING SYSTEM: The test material was classified according to Draize (1959) Dermal Toxicity. In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p. 47.

The test sites were scored according to the following scale:

ERYTHEMA AND ESCHAR FORMATION
- No erythema (0)
- Very slight eryhthema (barely perceptible) (1)
- Well defined eryhtema (2)
- Moderate to severe erythema (3)
- Severe eryhthema (beet redness) to slight eschar formation (injuries in depth) (4)

OEDEMA FORMATION
- No oedema (0)
-Very slight oedema (1)
- Slight oedema (edges of area well-defined by definite raising) (2)
- Moderate oedema (raised approximately 1 millimetre) (3)
- Severe oedema (raised maore than 1 millimetre and extending beyond the area of exposure (4)
Irritation parameter:
primary dermal irritation index (PDII)
Remarks:
Total score 19 giving average over 6 readings of 3.2
Basis:
mean
Time point:
other: average of all scores after 24 and 72hours
Score:
ca. 3.2
Reversibility:
fully reversible
Remarks:
14 days
Irritation parameter:
erythema score
Basis:
mean
Remarks:
values for rabbit 127 male
Time point:
other: mean of values at 24, 48 and 72 hours
Score:
ca. 1.33
Max. score:
2
Reversibility:
fully reversible within: 14
Remarks on result:
other: values at the 3 time points were 2, 1, and 1
Irritation parameter:
erythema score
Basis:
mean
Remarks:
values for rabbit no 122 male
Time point:
other: mean of values at 24, 48 and 72 hours
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: values at each of the 3 time points were 2, 2, and 2
Irritation parameter:
erythema score
Basis:
mean
Remarks:
values for rabbit no 125 male
Time point:
other: mean of values at 24, 48 and 72 hours
Score:
ca. 1.33
Max. score:
2
Reversibility:
not fully reversible within: 14days
Remarks on result:
other: values at the2 time points were 2, 1, and 1
Irritation parameter:
edema score
Basis:
mean
Remarks:
values for rabbit no127 male
Time point:
other: mean of values at 24, 48 and 72 hours
Score:
ca. 1.33
Max. score:
1
Reversibility:
fully reversible within: 7days
Remarks on result:
other: values at the 3 time points were 2, 1, and 1
Irritation parameter:
edema score
Basis:
mean
Remarks:
value for rabbit no 122 male
Time point:
other: mean of values at 24, 48 and 72 hours
Score:
ca. 2
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: values at the three time points were 2,2 and 2
Irritation parameter:
edema score
Basis:
mean
Remarks:
value for rabbit no 125 male
Time point:
other: mean of values at 24, 48 and 72 hours
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: values at three time points were 1, 1, and 1
Irritant / corrosive response data:
Well-defined erythema was noted at all treated skin sites one hour after patch removal and at the 24-hour observation. Well-defined erythema persisted at one treated skin site with very slight erythema at two treated skin sites at the 48 and 72-hour observations.
Slight oedema was noted at all treated skin sites one hour after patch removal with very slight to slight oedema at the 24, 48 and 72-hour observations.
Loss of skin elasticity was noted at one treated skin site at the 48 and 72-hour observations. Crust formation was noted at one treated skin site with slight desquamation at two treated skin sites at the 7-day observation.
Treated skin sites appeared normal at the 14-day observation.
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize PDII classification
Conclusions:
While some degree of irritation was observed, particularly in one animal, the degree of erythema an oedema was not of sufficient magnitude (mean values of <2) to warrant classification as a Skin Irritant Category 2 under CLP Regulation (EC) No. 1272/2008.

The relevant criteria which were NOT MET were
Mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or
(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or
(3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal

Executive summary:

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following: a) OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion- (adopted 17 July 1992) b) Commission Directive 92/69/EEC Method B4 Acute Toxicity (Skin Irritation). No corrosive effects were noted. However, a single 4-hour, semi-occlusive application of the test material to the intact skin of three rabbits produced well-defined erythema and slight oedema. Loss of skin elasticity, crust formation and slight desquamation were also noted.

Treated skin sites appeared normal at the 14-day observation.

Based on these data a primary irritation index of 3.2 was calculated and this classifies the test substance as a moderate irritant to rabbit skin according to the Draize classification scheme. However, in the three animals tested, the test material did not demonstrate a sufficient degree of erythema or oedema to warrant classification as a Category 2 Skin Irritant (i.e. mean values were all <2), and so is considered to be non-irritating under CLP Regulation (EC) No. 1272/2008 (Version 4.1, 2015).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A guideline study conducted in accordance with OECD test guideline 405 and to GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: Twelve to sixteen weeks old.
- Weight at study initiation: Weight range of 2.0 to 3.5 kg.
- Housing: The animal was housed in a suspended metal cage
- Environmental enrichment: wooden chew blocks and cardboard fun tunnels
- Diet (e.g. ad libitum): Free access to food
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL - approximately 74mg
Duration of treatment / exposure:
21 days
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
One
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done

SCORING SYSTEM: According to Draize Scale for Scoring Ocular Irritation at 1 hour, 24, 48 and 72 hours with additional observations at 27 and 21 days

TOOL USED TO ASSESS SCORE: Standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
ca. 1
Max. score:
1
Reversibility:
not fully reversible within: 21
Remarks on result:
other: individual scores at the three time points were 1, 1, and 1 - vacularisation of cornea still evident after 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible within: 14
Remarks on result:
other: scores at the three time points were 1, 1 and 1
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 14
Remarks on result:
other: scores at the three time points were 2, 2 and 2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
ca. 1.33
Max. score:
2
Reversibility:
fully reversible within: 14
Remarks on result:
other: scores at the three time points were 2, 1 and 1
Irritant / corrosive response data:
Scattered or diffuse corneal opacity was noted in the treated eye one hour after treatment and at subsequent 24, 48, 72-hour, 7, 14 and 21-day observations. Vascularisation of the cornea with a generalised in growth of vessels for approximately 2 to 3 mm was noted in the treated eye at the 7, 14 and 21-day observations.
Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-day observations.
Moderate conjunctival irritation was noted in the treated eye one hour alter treatment and at the 24, 48, 72-hour and 7-day observations.
The corneal vascularisation noted in the treated eye was considered to be irreversible.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: other: EU CLP
Conclusions:
The test material produced irreversible ocular damage and was considered to be a Category 1 eye irritant (irreversible effects on the eye) and requires the Hazard Statement H318 "Causes serious eye damage"
Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following: a) OECD Guidelines for the Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and b) Commission Directive 92/69/EEC Method B5 Acute Toxicity (Eye Irritation).

A single application of the test material to the non-irrigated eye of one rabbit produced irreversible effects. Reactions included scattered or diffuse corneal opacity, iridial inflammation, moderate conjunctival irritation and vascularisation of the cornea with a generalised ingrowth of vessels for approximately 2 to 3 mm.

The test material produced irreversible ocular damage and was considered to be a Category 1 eye irritant (irreversible effects on the eye) and requires the Hazard Statement H318 "Causes serious eye damage".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In both regulatory in vivo skin irritation studies, a single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and slight oedema. With the technical material effects were fully reversible in 14 days in 2 animals, but in the 3rd animal a light brown discolouration of the epidermis, loss of skin elasticity and flexibility, crust formation, reduced regrowth of fur, and a hardened light brown coloured scab was observed which prevented evaluation of erythema and oedema. These effects, together with a glossy skin were not fully reversible in 14 days for this animal. With the purified material there was a loss of skin elasticity, crust formation and slight desquamation, but treated skin sites in all three animals appeared normal at the 14-day observation time point.

 

Based on these data a primary irritation index of 3.2 was calculated and this classifies the test substance as a moderate irritant to rabbit skin according to the Draize classification scheme. However, in the three animals tested, the test material did not demonstrate a sufficient degree of erythema or oedema to warrant classification as a Category 2 Skin Irritant (i.e. mean values were all <2), and so is considered to be non-irritating under CLP Regulation (EC) No. 1272/2008.

 

A single application of the test material to the non-irrigated eye of one rabbit produced irreversible effects. Reactions included scattered or diffuse corneal opacity, iridial inflammation, moderate conjunctival irritation and vascularisation of the cornea with a generalised ingrowth of vessels for approximately 2 to 3 mm which was not reversible after 21 days observation.

 

The test material produced irreversible ocular damage and was considered to be a Category 1 eye irritant (irreversible effects on the eye) and requires the Hazard Statement H318 "Causes serious eye damage".


Justification for selection of skin irritation / corrosion endpoint:
Guideline study conducted according to OECD404 and EU B.4 and to GLP. The study is the most recent of two similar studies in which a purified test material was used in the selected key study in comparison with technical material used in the supporting study.

Justification for selection of eye irritation endpoint:
A guideline study conducted in accordance with OECD test guideline 405 and to GLP.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Decan-1,2-diol was not classifiable as a skin irritant under CLP Regulation (EC) No. 1272/2008 since, for the three animals tested in each of the two studies the mean values for erythema/eschar or oedema were all <2.

However, decan-1,2-diol did produce irreversible ocular damage and was considered to be a Category 1 eye irritant (irreversible effects on the eye) and requires the Hazard Statement H318 "Causes serious eye damage".

Not classifiable as a Skin Irritant