Registration Dossier

Administrative data

Description of key information

Skin irritation using read across from Citronellol (OECD TG 404): irritating

Eye irritation (OECD TG 438): irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
study acquired from reliable secondary source therefore no detailed documentation.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
not specified
Remarks:
Albino
Details on test animals and environmental conditions:
Not specified.
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 100%
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
Test 1: 3 animals
Test 2: 4 animals
Test 3: 4 animals
Details on study design:
Multi patch studies were selected for this publication because the multi-patch studies were assumed not to contravene with OECD Test Guideline 404. Additionally, no interference was reported between reactions on different patch sites in the multi-patch studies.

TEST SITE
- Area of exposure: Flank
- % coverage: Not specified
- Type of wrap if used: Semi-occlusive patches (multi-patch)

OBSERVATION TIME POINTS
After 1, 24, 48, 72h and 7 days.

SCORING SYSTEM: according to Draize (adopted by OECD TG 404)
Irritation parameter:
erythema score
Remarks:
Test 1
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 1
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 1
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 1
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 1
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 1
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
De = desquamation from skin surface (De* = marked) (Des = slight)

Test 1:
- On Day 7 the following observations were reported for animal 1, 2, and 3: De*, De, and De*, respectively.
Test 2:
- On day 7 the following observations were reported for animal 1, 2, 3, and 4: De, none, De, and De, respectively.
Test 3:
- After 48 and 72h the following observations were reported for animal 1, 2, 3, and 4: none, none, Des, and none, respectively.
- On day 7 the following observations were reported for animal 1, 2, 3, and 4: none, none, De*, and De*, respectively.
Interpretation of results:
other: Irritating to skin (Category 2)
Remarks:
Based on CLP criteria (EC 1272/2008 and its updates)
Conclusions:
Under the test conditions (OECD 404 and GLP) the test substance is considered to be a skin irritant.
Executive summary:

The skin irritation potential of Citronellol has been tested according to OECD TG 404. Two multi patch test were performed with 4 rabbits each and one single patch test was performed with 3 rabbits. All studies were performed with 0.5 mL undiluted test substance applied on the flank for 4 hours under semi-oclussive conditions. The animals were observed for 7 days after exposure and skin irritation was scored according to the Draize scoring system. Under the conditions of the test the substance was found to be skin irritating.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
study acquired from reliable secondary source therefore no detailed documentation.
Justification for type of information:
The read across justification is presented in the irritation / corrosion endpoint summary and the accompanying files are also attached there.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Remarks:
Test 1
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 1
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 1
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 1
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 1
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 1
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 2 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 2 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Test 3 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Remarks:
Test 3 (multi patch)
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Interpretation of results:
other: Irritating to skin (Category 2)
Remarks:
Based on CLP criteria (EC 1272/2008 and its updates)
Conclusions:
Under the test conditions (OECD 404 and GLP) the test substance is considered to be a skin irritant.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 Aug 2017 to 18 Aug 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Version / remarks:
26 July 2013
GLP compliance:
yes (incl. certificate)
Remarks:
Triskelion B.V., Utrechtseweg 48, 3700 AV, Zeist
Species:
other: Eyes of male or female chickens (ROSS, spring chickens)
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: Slaughterhouse v.d. Bor, Nijkerkerveen, The Netherlands
- Characteristics of donor animals: Approximately 7 weeks old, male or female chickens, body weight range approximately 1.5-2.5 kg, were used as eye donors.
- Storage, temperature and transport conditions of ocular tissue: Heads of the animals were cut off immediately after sedation of the animals by electric shock and incision of the neck for bleeding, and before they reached the next station on the process line. The heads were placed in small plastic boxes on a bedding of paper tissues moistened with isotonic saline. Next, they were transported to the testing facility. During transportation, the heads were kept at ambient temperature.
- Time interval prior to initiating testing: Within 2 hours after kill, eyes were carefully dissected and placed in a superfusion apparatus.
- Indication of any existing defects or lesions in ocular tissue samples: No
- Indication of any antibiotics used: No
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
30 μL neat substance
Duration of treatment / exposure:
10 seconds
Duration of post- treatment incubation (in vitro):
240 minutes
Number of animals or in vitro replicates:
Test group and positive control: in triplicate
Negative control: single
Details on study design:
SELECTION AND PREPARATION OF ISOLATED EYES
Within 2 hours after kill, eyes were carefully dissected and placed in a superfusion apparatus using the following procedure: First the eye-lids were carefully removed without damaging the cornea and a small drop of Fluorescein sodium 2.0% w/v was applied to the corneal surface for a few seconds and subsequently rinsed off with isotonic saline at ambient temperature. Next, the head with the fluorescein-treated cornea was examined with a slit-lamp microscope (Slit-lamp 900 BP, Haag-Streit AG, Liebefeld-Bern, Switzerland) to ensure that the cornea was not damaged. If undamaged (e.g., fluorescein retention and corneal opacity scores of ≤ 0.5), the eye was further dissected from the head without damaging the eye or cornea. Care was taken to remove the eye-ball from the orbit without cutting off the optical nerve too short. The enucleated eye was placed in a stainless steel clamp with the cornea positioned vertically and transferred to a chamber of the superfusion apparatus. The clamp holding the eye was positioned in such a way that the entire cornea was supplied with isotonic saline from a bent, stainless steel tube, at a target rate of 0.10-0.15 mL/min. The chambers of the superfusion apparatus as well as the saline were temperature controlled at approximately 32 °C (water pump set at 36.4 °C). After placing in the superfusion apparatus, the eyes were examined again with the slit-lamp microscope to ensure that they were not damaged. An accurate measurement was taken at the corneal apex of each eye. Eyes with a corneal thickness deviating more than 10% of the average corneal thickness of the eyes, eyes showing opacity (score higher than 0.5), or were unacceptably stained with fluorescein (score higher than 0.5) indicating the cornea to be permeable, or eyes that showed any other signs of damage, were rejected as test eyes and replaced.

EQUILIBRATION AND BASELINE RECORDINGS
Each eye provided its own baseline values for corneal swelling, corneal opacity and fluorescein retention. For that purpose, after an equilibration period of 45-60 minutes, the corneal thickness of the eyes was measured again to determine the zero reference value for corneal swelling calculations.

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: 20 mL saline. After rinsing, each eye in the holder was returned to its chamber.
- Indicate any deviation from test procedure in the Guideline: none

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Slit-lamp microscope examination
- Damage to epithelium based on fluorescein retention: Slit-lamp microscope examination
- Swelling: measured with optical pachymeter on a slit-lamp microscope; slit-width setting: set at 0.095 mm
- Others: After the final examination, the test substance treated eyes, the negative and positive control eyes were preserved in a neutral aqueous phosphate-buffered 4% solution of formaldehyde. The corneas were embedded in paraffin wax, sectioned at ca 4 μm and stained with PAS (Periodic Acid-Schiff). The microscopic slides were subjected to histopathological examination.

SCORING SYSTEM:
Defined scoring scales were used for each parameter to define the severity of effects into four categories (I-IV).
- Mean corneal swelling (%): According to OECD 438 guideline. Examination of the eyes after 0, 30, 75, 120, 180, and 240 minutes
- Mean maximum opacity score: According to OECD 438 guideline. Examination of the eyes after 0, 30, 75, 120, 180, and 240 minutes
- Mean fluorescein retention score at 30 minutes post-treatment: According to OECD 438 guideline.

DECISION CRITERIA: According to OECD 438 guideline
Irritation parameter:
percent corneal swelling
Run / experiment:
slit-lamp examination
Value:
14
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: maximum mean values
Irritation parameter:
cornea opacity score
Run / experiment:
slit-lamp examination
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: maximum mean values
Irritation parameter:
fluorescein retention score
Run / experiment:
slit-lamp examination
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: maximum mean values
Other effects / acceptance of results:
Slit-lamp examination: The test substance caused corneal effects consisting of slight corneal swelling (mean of 14%), moderate opacity (mean score of 2.0) and moderate fluorescein retention (mean score of 2.0). The negative control eye did not show any corneal effect and demonstrated that the general conditions during the tests were adequate. The positive control BAC 5% caused severe corneal effects and demonstrated the ICE test valid to detect severe eye irritants.

Microscopic examination of the corneas revealed slight erosion, moderate necrosis and very slight (2/3 corneas) or slight (1/3 corneas) vacuolation of the epithelium. In addition, basophilic spherical inclusions were observed in the superficial epithelial layer of the three corneas, and two corneas showed a focal wedge of necrotic cells up to the basement membrane. Currently, no criteria to interpreted the histopathological findings for this type of chemical exist. Microscopic examination of the cornea treated with the negative control (saline) did not reveal any abnormalities. Microscopic examination of the corneas treated with the positive control BAC 5% generally revealed severe erosion and very slight vacuolation of the epithelium.
Interpretation of results:
other: Irritating to eyes (Category 2)
Remarks:
Based on CLP criteria (EC 1272/2008 and its updates)
Conclusions:
Under the test conditions (OECD 438 and GLP) the test substance is considered to be an eye irritant.
Executive summary:

The test substance was examined for its in vitro eye irritating potential using the Isolated Chicken Eye (ICE) test, in accordance with OECD guideline 438 and GLP. In the ICE test, 3 eyes were exposed to 30 µL test substance for 10 seconds. In addition, one negative control eye (30 µL saline) and three positive control eyes (30 µL 5% Benzalkonium Chloride (BAC)) were tested. After the exposure, the eyes were rinsed with 20 mL saline and were examined at approximately 0, 30, 75, 120, 180, and 240 minutes after treatment. Mean fluorescein retention score was determined at 30 minutes post-treatment. The test substance caused corneal effects consisting of slight corneal swelling (mean of 14%), moderate opacity (mean score of 2.0) and moderate fluorescein retention (mean score of 2.0). The negative control eye did not show any corneal effect and demonstrated that the general conditions during the tests were adequate. The positive control BAC 5% caused severe corneal effects and demonstrated the ICE test valid to detect severe eye irritants. Microscopic examination of the corneas treated with the test substance revealed slight erosion, moderate necrosis and very slight (2/3 corneas) or slight (1/3 corneas) vacuolation of the epithelium. In addition, basophilic spherical inclusions were observed in the superficial epithelial layer of the three corneas, and two corneas showed a focal wedge of necrotic cells up to the basement membrane. Currently, no criteria to interpreted the histopathological findings for this type of chemical exist. Microscopic examination of the cornea treated with the negative control (saline) did not reveal any abnormalities. Microscopic examination of the corneas treated with the positive control BAC 5% generally revealed severe erosion and very slight vacuolation of the epithelium. Based on these results, the substance is considered to be an eye irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

The skin irritation potential of Geranium oil was assessed by using read across from Citronellol (CAS no. 106-22-9). First, the experimental information of Citronellol for skin irritation and Geranium oil for eye irritation will be summarised. Thereafter the read across justification is presented. The accompanying files are attached in the present endpoint summary.

 

Skin irritation (read across to Citronellol)

The skin irritation potential of Citronellol has been tested according to OECD TG 404. Two multi patch test were performed with 4 rabbits each and one single patch test was performed with 3 rabbits. All studies were performed with 0.5 mL undiluted test substance applied on the flank for 4 hours under semioclussive conditions. The animals were observed for 7 days after exposure. Under the conditions of the test the substance was found to be skin irritating.

 

Eye irritation

The test substance was examined for its in vitro eye irritating potential using the Isolated Chicken Eye (ICE) test, in accordance with OECD guideline 438 and GLP. In the ICE test, 3 eyes were exposed to 30 µL test substance for 10 seconds. In addition, one negative control eye (30 µL saline) and three positive control eyes (30 µL 5% Benzalkonium Chloride (BAC)) were tested. After the exposure, the eyes were rinsed with 20 mL saline and were examined at approximately 0, 30, 75, 120, 180, and 240 minutes after treatment. Mean fluorescein retention score was determined at 30 minutes post-treatment. The test substance caused corneal effects consisting of slight corneal swelling (mean of 14%), moderate opacity (mean score of 2.0) and moderate fluorescein retention (mean score of 2.0). The negative control eye did not show any corneal effect and demonstrated that the general conditions during the tests were adequate. The positive control BAC 5% caused severe corneal effects and demonstrated the ICE test valid to detect severe eye irritants. Microscopic examination of the corneas treated with the test substance revealed slight erosion, moderate necrosis and very slight (2/3 corneas) or slight (1/3 corneas) vacuolation of the epithelium. In addition, basophilic spherical inclusions were observed in the superficial epithelial layer of the three corneas, and two corneas showed a focal wedge of necrotic cells up to the basement membrane. Currently, no criteria to interpreted the histopathological findings for this type of chemical exist. Microscopic examination of the cornea treated with the negative control (saline) did not reveal any abnormalities. Microscopic examination of the corneas treated with the positive control BAC 5% generally revealed severe erosion and very slight vacuolation of the epithelium. Based on these results, the substance is considered to be an eye irritant.

Read across justification

Essential oil of geranium obtained from aerial parts of Pelargonium graveolens by steam distillation (Geranium oil, CAS no: 90082-51-2) (target) and its skin irritating properties using read across from dl-Citronellol, CAS no: 106-22-9 (source)

 

Introduction and hypothesis for the constituent-based read acrossapproach

Geranium oil is a UVCB which consists of hydrocarbon constituents. Its major constituent is dl-Citronellol (C=C double bond and OH group). For Geranium oil (target) no skin irritation data are available. In accordance with Article 13 of REACH,lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read across. For assessing the skin irritating properties of Geranium oil, the constituent-based read-across approach is selected based on the known skin irritant effects of the main constituents of Geranium oil.

Hypothesis:Geranium oil (target)is expected to have similar skin irritating properties as dl-Citronellol (source).

Available information:The source substance dl-Citronellol, CAS no: 106-22-9 has been tested in an OECD TG 404, GLP study. Two multi-patch tests (more than one chemical was tested on the same rabbit at the same time) were performed with 4 rabbits each and one single-patch test was performed with 3 rabbits. All studies were performed with 0.5 mL undiluted test substance applied on the flank for 4 hours under semi-occlusive conditions. The animals were observed for 7 days after exposure. At all patches the substance was found to be skin irritating (Skin Irrit. 2).

Target and Source chemical(s): The information on Geranium oil (target) and the analogue information from dl-Citronellol (source) are presented in data matrix 1 of this document. This includes the chemical structure of the source, physico-chemical properties and toxicological information relevant for skin irritation.

Purity / Impurities:

The impurities are not relevant for the target substance Geranium oil as it is a UVCB (Naturally Complex Substance). The purity of dl-Citronellol is 98.7% (ECETOC TR No.66).

Analogue justification

According to REACH Annex XI an analogue approach and structural alert information can be used to replace testing when information from different sources provides sufficient evidence to conclude that this substance has or does not have a particular dangerous property. The result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.

Analogue selection:As a UVCB, Geranium oil (target) consists of various constituents that are present in variable ranges, as shown in data matrix 2. A majority of the constituents present in this UVCB (dl-Citronellol, Citronellylformate, Geraniol, (+)-isomenthone, Linalool, (-)-rose oxide, (-)-menthone, Geranyl formate, Citronellyl butyrate)are assigned as skin irritants in the C&L-inventory on the ECHA website. For pragmatic reasons, dl-Citronellol,is selected as a source because of itshigh typical concentration range (up to 43.00% w/w) in the Geranium oil and its skin irritation. dl-Citronellol, being an alcohol, represents other alcohols, esters and other functional groups, because most of these are skin irritants.

Irritation potential: The potential for irritation by most of the terpene alcohols has been well characterized in both humans and in laboratory animals, and considered a likely result of their skin permeability in combination with the formation of oxidation products which initiate an irritant biological response.

Skin permeability: for organic substances (except for the highly reactive), the mechanism behind skin irritation can be described as a process based on two phases as described by Walker et al. (2004)1. First, a substance penetrates the stratum corneum. Subsequently a biological reactive response is triggered in the deeper layers of the epidermis or the dermis causing the irritation. The skin absorption potential of all Geranium oil constituents is similar to dl-Citronellol because the (estimated) physico-chemical properties are similar (see data-matrix).

Reactivity: Geranium oil is reactive because its key (dl-Citronellol) and other constituents are reactive and therefore have skin irritation properties. In view of the reactive potential of dl-Citronellol,a classification is warranted.

Remaining uncertainties: There are no remaining uncertainties: the Geranium oil is a skin irritant because its key constituent and the other constituents are skin irritants. Besidesdl-Citronellol,some other constituents in this UVCB are also known as skin irritant (Category 2).

Conclusion for skin irritation

For Geranium oil, a UVCB, the potential for skin irritation was derived from dl-Citronellol, which is its key constituent and which is a representative for other constituents in the oil. Citronellol was tested in anOECD TG 404 GLP study) and was found to be skin irritating (Skin Irrit. 2).

Final conclusion on Geranium oil: Substance is a skin irritant (Category 2).

 

Data matrix 1. Information important for assessment of skin irritating properties for the read across from dl-Citronellol (Source) to Geranium oil (Target)

 

CHEMICAL NAME

Geranium oil (Target)

dl-Citronellol (Source)*

Molecular structure

N/A

 

CAS

90082-51-2

106-22-9

REACH registration

To be registered (Annex VII)

REACH registered

EINECS

290-140-0

203-375-0

Molecular formula

N/A

C10H20O

Molecular weight

N/A

156.27 g/mol

Physico-chemical properties

Appearance

Clear Liquid (IFF, 2006)

Liquid

Melting point (˚C)

<-20 +/- 1 (IFF, 2016)

< -20

Vapour pressure (Pa)

39.3 +/- 0.3 measured at 24 °C (IFF, 2004)

8.6 at 20 °C (estimated)

100 at 67 °C (measured)

Exp. Water solubility (mg/l)

607.1 +/- 15.1 at 24°C (IFF, 2004)

307 at 25 °C

Exp. Log Kow

3.5-3.9 +/-0.1 at 25 °C (IFF, 2016)

3.41 at 25 °C

Human health

 

Skin irritation

Read across

 

Skin irritant Cat. 2

(OECD TG 404)

Eye irritation

Eye irritant Cat. 2

(OECD TG 438)

Eye irritant Cat. 2,

 (OECD TG 405)

Sensitisation

Skin sensitiser Cat.1B(OECD TG 429)

Skin sensitiser Cat.1B(OECD TG 429)

* Hazard properties from ECHA disseminated dossier (accessed March 2018)

 

Data matrix 2. Composition and endpoint specific constituent classifications of Target and Source

NAME

CAS

Geranium oil

Min max range of both qualities (Egypt and China) together

TARGET

dl-Citronellol

 

SOURCE

Skin irritant (notified*)

dl-Citronellol

106-22-9

16.00%

43.00%

 98.7%

Skin Irrit. 2 / H315

Citronellyl formate

105-85-1

 2.00%

14.00%

-

Skin Irrit. 2 / H315

Geraniol

106-24-1

 5.00%

24.00%

-

Skin Irrit. 2 / H315

(+)-isomenthone

491-07-6

 3.50%

13.00%

-

Skin Irrit. 2 / H315

Guaiadiene

N/A

< 0.01%

14.00%

-

Not available

Linalool

78-70-6

 1.00%

10.00%

-

Skin Irrit. 2 / H315

(-)-rose oxide

3033-23-6

 1.00%

 4.00%

-

Skin Irrit. 2 / H315

(-)-menthone

89-80-5

< 0.01%

 3.00%

-

Skin Irrit. 2 / H315*

Geranyl formate

105-86-2

 1.00%

 8.00%

-

Skin Irrit. 2 / H315*

Citronellyl butyrate

141-16-2

< 0.01%

 2.00%

-

Skin Irrit. 2 / H315*

Citronellyl propionate

141-14-0

< 0.01%

 2.00%

-

No

Geranyl tiglate

7785-33-3

< 0.01%

 4.00%

-

No

Germacrene D

37839-63-7

< 0.01%

 4.00%

-

No

Other minor and unknown constituents :

Including beta-bourbonene; beta-caryophyllene; delta-cadinene; 1(5)-guaien-11-ol; phenylethyl tiglate; geraniol butanoate

N/A

10.00%

30.00%

-

-

Unknown

N/A

-

-

1.3%

-

*CLP notifications in C&L inventory, however not classified in REACH dossier (March 2018)

 

References:

1.      Walker JD, Gerner I, Hulzebos E and Schlegel K (2004) (Q)SARs for Predicting Skin Irritation and Corrosion: Mechanisms, Transparency and Applicability of Predictions. QSAR Comb Sci 20 23:721-5.

Justification for classification or non-classification

Based on the available data, the substance is classified for skin irritation (Skin Irrit. 2 / H315) and eye irritation (Eye Irrit. 2 / H319) in accordance with the criteria outlined in EU CLP (EC no 1272/2008 and its amendments).


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