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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Irritation/corrosion:
- skin: not irritating (Toxicol Labs Limited 1985)
- eye: irritating (BASF 1972, XXI/221)

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: Acceptable report performed according to current guidelines
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A. Smith, 7 Kydcomb Road, Warlingham, Surrey
- Housing: individually
- Diet: ad libitum
- 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, intact
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
- Concentration (if solution): 100%
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48, 72 h; 7 d
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: dorsal skin
- Type of wrap if used: placed evenly over a 2.5 cm square of surgical lint B.P placed onto a 6 cm square area of clipped, intact dorsal skin. The lint patches were held in place by encircling the trunk of the animals with a length of 'Elastoplast' elastic adhesive bandage 10 cm wide.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with warm water
- Time after start of exposure: 4 h


SCORING SYSTEM:
Irritation was assessed and allocated a numerical value based on the following:
- Erythema and Eschar Formation
No erythema = 0;
Very slight erythema (barely perceptible) = 1;
Well-defined erythema = 2;
Moderate to severe erythema = 3;
Severe erythema (beet redness) to slight eschar formation (injuries in depth) = 4.

- Oedema Formation:
No oedema = 0;
Very slight oedema (barely perceptible) = 1;
Slight oedema (edges of area well-defined by definite raising) = 2;
Moderate oedema (raised approximately 1 mm) = 3;
Severe oedema (raised more than 1 mm and extending beyond area of exposure) = 4.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48, 72 h
Score:
0.8
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 7 d

Readings Animal Erythema Edema Further findings
1h 1 1 0 slight yellow staining
2 0 0 -
3 0 0 -
4 1 0 -
24h 1 2 1 -
2 0 0 -
3 1 0 -
4 1 0 -
48h 1 2 0 -
2 0 0 -
3 1 0 -
4 1 0 -
72h 1 1 0 -
2 0 0 -
3 0 0 -
4 1 0 -
7d 1 0 0 -
2 0 0 -
3 0 0 very slight desquamation
4 0 0 -
Mean (24h-72h) 1 1.7 0.3  
2 0 0  
3 0.7 0  
4 1 0  
Mean (24h-72h) all animals 0.8 0.1  
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: Acceptable, well documented study report which meets basic scientific principles, not according to current guidelines
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Internal BASF method was used
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: male 3.19 kg, female 3.44 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: NaCl into other eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µl
- Concentration (if solution): 100%
Duration of treatment / exposure:
continuously
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Details on study design:
SCORING SYSTEM:
Gradings for corneal opacity, conjunctival redness and chemosis were converted into numerical grading system acc. to Draize.

Chemosis (Swelling) and cornea (Opacity):
0 = none
1 = slight
2 = well defined
3 = severe
4 = very severe


Conjunctival redness (Redness):
0 = normal
1 = slight
2 = well defined
3 = severe
4= very severe
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 72 h
Score:
1.25
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within:
Remarks on result:
other: 72 h
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 d

Animal 1: male

Animal 2: female

Results:

Readings Animal Erythema chemosis Corneal opacity Additional findings
1h 1 2 1 1 miosis
2 2 3 2 miosis
3 h 1 2 1 1 discharge
2 2 2 2 discharge
24 h 1 1 1 2 mucosal hemorrhages
2 2 1 2 mucosal hemorrhages
72 h 1 1 0 1 mucosal hemorrhages
2 1 0 3 mucosal hemorrhages, scar
4 d 1 1 0 1 mucosal hemorrhages
2 1 0 3 mucosal hemorrhages, scar
7 d 1 1 0 1  
2 1 0 1 scar
8 d 1 1 0 1  
2 1 0 1 scar
Mean 24 - 72 h 1 1 0.5 1.5  
2 1.5 0.5 2.5  
Mean   1.25 0.5 2

No effects reported for iris.

No effects observed for eyes treated with NaCl.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In the chosen key study for skin irritation, according to EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion) and GLP, four rabbits were treated with 0.5 mL of undiluted hydroxycitronellal for 4 hours under semiocclusive conditions (Toxicol Labs Limited, 1985). After 1, 24, 48, 72 hours and 7 days, applications sites were evaluated for erythema and edema. Mean scores for erythema (24, 48, 72 hours) were 1.7, 0, 0.7 and 1 for each animal respectively. Mean scores for edema (24, 48, 72 hours) were 0.3, 0, 0 and 0 for each animal respectively. All effects were fully reversible within 7 days. Overall, application of undiluted hydroxycitronellal resulted in slight and reversible skin irritation under the chosen testing conditions.

In a supporting study, equivalent to EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion) and GLP (reversibility not fully assessed), 0.5 ml of undiluted hydroxycitronellal was applied dermally under semi-occlusive conditions to three rabbits for 4 hours (Toxicol Labs Limited 1984). The application sites were evaluated 1, 24, 48, 72 hours and 7 days for erythema and edema. Mean scores for erythema (24, 48, 72 hours) were 1, 1, and 0.7 for each animal respectively. Mean scores for edema (24, 48, 72 hours) were 0.3, 0.3 and 0 for each animal respectively. Erythema were not fully reversible within 7 days, however a tendency of reversibility is indicated based on the single animal data given. Overall, application of undiluted hydroxycitronellal resulted in slight skin irritation under the chosen testing conditions.

In a skin irritation study, undiluted hydroxycitronellal was applied for 1, 5, 15 min and 20 h to the back of two Vienna White rabbits under occlusive conditions (BASF 1972; XXI/221). Sites were evaluated for the following eight days. Signs of skin irritation and desquamation were only observed after 20 h of exposure. Mean erythema score was 2 (24 -72 h) for each animal respectively, but was fully reversible after 8 days. No edema was observed. Desquamation was still present after 8 days. The effects observed were found after exposure conditions representing a worst case (occlusive, 20 hours exposure) and are not in line with current standard protocols.

A broad variety of studies in literature mainly from secondary sources are available, addressing skin irritation of hydroxycitronellal, but were not considered for this assessment, as these studies did not follow current standard protocols, used the test substance in dilutions only, and/or were of limited documentation. Within these studies, numerous irritancy-screening studies have been carried out for concentration selection for skin sensitization tests. Additionally, hydroxycitronellal was part of test substance panels for different in vitro test validation studies, with diverging findings.

Overall, on the basis of the present studies in vivo, that were performed according to current guidelines, hydroxycitronellal was found to be only slightly irritating to skin.

Data from studies in literature with human volunteers confirmed a slight irritation potential. Hydroxycitronellal was mildly irritating at 32% in acetone after a 48 hour occlusive application (Motoyoshi 1979) and 2/22 positive reactions were observed after a 24 hour closed patch application of undiluted hydroxycitronellal (Katz 1946). A broad variety ofirritancy screening tests carried out prior to human skin sensitization are availablein literature mainly from secondary sources and partially confirmed these dermal effects dependent on the chosen application conditions, e.g. occlusive, vehicle and concentrations used (not included into this assessment).

Eye irritation:

In the chosen key study for eye irritation according to an internal BASF method, 50 µl of undiluted hydroxycitronellal was applied to eyes of two Vienna White rabbits. Reactions were evaluated for eight days (BASF 1972, XXI/221). As result, mean scores (24, 72 hours) for corneal opacity, conjunctival redness and chemosis were 1.5, 1 and 0.5, for animal 1 and 2.5, 1.5 and 0.5 for animal 2, respectively. Conjunctival redness and corneal opacity were not reversible within the eight day observation period. Hydroxycitronellal has been found to be irritating to eyes under the chosen testing conditions.

In an supportive eye irritation study in rabbits from secondary source, 6 New Zealand white rabbits were treated with 0.1 mL of undiluted hydroxycitronellal (no data on purity given) and observed for 7 days (TSCATS, 1991). Mean scores (24, 48, 72 hours over all animals) for corneal opacity, iris, conjunctiva and chemosis score were 0, 0.8, 1.2 and 0.8, respectively and fully reversible within 7 days. A mild eye irritating effect was observed.

 

In an eye irritation study in rabbits from secondary source, 3 rabbits were treated with 0.1 mL of 5% hydroxycitronellal (diluent unknown). Eyes of additional animals were washed with warm water after 2 and 4 seconds, respectively. Mean scores of continuously treated animals (24, 48, 72 hours over all animals) were 0, 0, 1.4, 0.9 for corneal opacity, iris, conjunctiva and chemosis, respectively. All findings were reversible within 7 days. In animals treated with the test substance for 2 or 4 seconds, comparable reversible conjunctival redness and chemosis was found. Overall, mild and reversible eye irritation potential has been observed for diluted hydroxycitronellal under the chosen testing conditions.

Overall, hydroxycitronellal was determined to be irritating to eyes.

Justification for classification or non-classification

The present data on skin irritation do not fulfill the criteria laid down in regulation (EU) 1272/2008, and therefore, a non-classification is warranted.

The present data on eye irritation fulfill the criteria laid down in regulation (EU) 1272/2008. Therefore, a classification "eye irritant" (category 2) is warranted.