Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 231-327-9 | CAS number: 7493-57-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Skin sensitisation: not sensitising (read-across from Hyacinth body tested in OECD TG 429)
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29 September 2016 - 08 November 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The skin sensitization information of this source substance is used for read across to Hyacinth body #3.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- July 2010
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- May 2008
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Female CBA/J strain mice were supplied by Janvier, Le Genest-Saint-Isle, France.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: approximately ten weeks old
- Weight at study initiation: 19.3 to 24.7 g
- Housing: Animals were group housed in labeled Makrolon cages containing sterilised sawdust as bedding material. Paper and shelters were supplied as cage-enrichment. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study
- Diet (e.g. ad libitum): ad libitum (pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days
- Other: On receipt the animals were randomly allocated to cages.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70 - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Undiluted test item or the test item at concentrations of 2%, 10% or 30% v/v in vehicle.
- No. of animals per dose:
- Groups of five mice were treated.
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: soluble up to the maximum required concentration
- Irritation assessment: Once daily on Days 1-6 (on Days 1-3 within 1 hour after dosing) according to the numerical scoring system.
- Systemic toxicity assessment: Once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing). Any signs of toxicity or signs of ill health during the test were recorded.
- Ear thickness measurements: Ear thickness measurements were conducted using a digital thickness gauge (Kroeplin C110T-K) prior to dosing on Days 1 and 3, and on Day 6. Animals were sacrificed after the final observation.
- Other information: Initially, two test item concentrations were tested; a 30% and 100% concentration. The highest concentration was the maximum concentration as required in the test guidelines. Based on the results of the initially treated animals, two additional animals were treated in a similar manner with an intermediate concentration (50%) at a later stage.The test system, procedures and techniques were identical to those used in the main study except that the animals were approximately 10-11 weeks (at initiation of treatment) and that the assessment of lymph node proliferation and necropsy were not performed. Two young adult animals per concentration were selected. Each animal was treated with one concentration on three consecutive days.
MAIN STUDY
- Test Item Administration: Groups of five mice were treated with the undiluted test item or the test item at concentrations of 2 %, 10 % or 30 % v/v in acetone/olive oil 4:1. The maximum concentration of 30% was chosen due to expected systemic toxicity at higher levels. The vehicle was selected on the basis of maximizing the solubility using the test item data provided by the Sponsor and trial preparation results performed at Charles River Den Bosch. The vehicle was chosen from the vehicles specified in the test guideline. There was no information available regarding the solubility or stability in vehicle. No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement. The preliminary screening test suggested that the test item would not produce systemic toxicity or excessive local irritation at the highest suitable concentration. The dorsal surface of both ears was topically treated (25 μL/ear) with the test item, at approximately the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing. A further group of five mice received the vehicle alone in the same manner.
TREATMENT PREPARATION AND ADMINISTRATION:
Induction - Days 1, 2 and 3
The dorsal surface of both ears was topically treated (25 μL/ear) with the test substance, at approximately the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing.
3H-Methyl Thymidine Administration
Five days following the first topical application of the test item, each animal was injected via the tail vein with 0.25 mL of sterile phosphate buffered saline (PBS) (Merck, Darmstadt, Germany) containing 20 μCi of 3H-methyl thymidine (PerkinElmer Life and Analytical Sciences, Boston, MA, US).
Terminal Procedures - Day 6
Termination: After five hours, all animals were killed by intraperitoneal injection (0.2 mL/animal) of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands). The draining (auricular) lymph node of each ear was excised. The relative size of the nodes (as compared to normal) was estimated by visual examination and abnormalities of the nodes and surrounding area were recorded. The nodes were pooled for each animal in approximately 3 mL PBS.
Preparation of Single Cell Suspension: Following excision of the nodes, a single cell suspension of lymph node cells (LNC) was prepared in PBS by gentle separation through stainless steel gauze (diameter: 125 μm). LNC were washed twice with an excess of PBS by centrifugation at 200g for 10 minutes at 4ºC. To precipitate the DNA, the LNC were exposed to 5% trichloroacetic acid (TCA) (Merck, Darmstadt, Germany) and then stored in the refrigerator until the next day.
Determination of 3HTdR Incorporation: Precipitates were recovered by centrifugation, resuspended in 1 mL TCA and transferred to 10 mL of Ultima Gold cocktail (PerkinElmer Life and Analytical Sciences, Boston, MA, US) as the scintillation fluid. Radioactivity measurements were performed using a Packard scintillation counter (2800TR). Counting time was to a statistical precision of ± 0.2% or a maximum of 5 minutes whichever came first. The scintillation counter was programmed to automatically subtract back ground and convert Counts Per Minute (CPM) to Disintegrations Per Minute (DPM).
Observations
Mortality/Viability: Twice daily.
Clinical Observations: Once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing). Any signs of toxicity or signs of ill health during the test were recorded.
Controls:
The positive control animals were similarly treated to the test animals except that 25 μL of the positive control item, α Hexylcinnamaldehyde, techical grade, at a concentration of 5, 10 and 25 % v/v in acetone/olive oil 4:1 was applied to the dorsal surface of each ear. The positive control group served as common control with another study according to the summary of positive control data for the local lymph node assay.
Bodyweights: The bodyweight of each mouse was recorded on Day 1 (prior to dosing) and on Day 6 (prior to termination). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Not performed.
- Positive control results:
- The positive control item, α-Hexylcinnamaldehyde, techical grade, gave a Stimulation Index of greater than 3 (4.3) when tested at a concentration of 25 % v/v in acetone/olive oil 4:1.
- Key result
- Parameter:
- EC3
- Remarks:
- %
- Remarks on result:
- other: EC3 was not reached
- Remarks:
- tested up to 30%, which was the highest tolerable dose, above which systemic effects were seen
- Parameter:
- SI
- Value:
- 0.9
- Test group / Remarks:
- 2%
- Parameter:
- SI
- Value:
- 1.1
- Test group / Remarks:
- 10%
- Parameter:
- SI
- Value:
- 1.3
- Test group / Remarks:
- 30%
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION:
The SI values calculated for the test item concentrations 2, 10 and 30% were 0.9, 1.1 and 1.3, respectively.
EC3 CALCULATION:
There was no indication that the test item elicits a SI ≥ 3 when tested up to 30%, therefore Hyacinth body was not considered to be a skin sensitizer. It was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 30%.
CLINICAL OBSERVATIONS/BODY WEIGHTS:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. - Interpretation of results:
- other: Not sensitising
- Remarks:
- Based on CLP criteria (EC 1272/2008 and its updates)
- Conclusions:
- The SI values calculated for Hyacinth body concentrations 2, 10 and 30% were 0.9, 1.1 and 1.3, respectively. These results show that Hyacinth body does not elicit an SI ≥ 3. An EC3 value could not be derived . Based on the results of this study, it is concluded that Hyacinth body is not a skin sensitizer.
- Executive summary:
The skin sensitisation potential of Hyacinth body has been tested according to OECD TG 429: Local Lymph Node Assay method. As this is a guideline study performed under GLP conditions, the study was assigned a Klimisch 1 score. In the pre-screen test at 50% piloerection and slight erythema were noted and at 100% piloerection, hunched posture, very slight to well-defined erythema and scaliness were noted. No signs of systemic toxicity were noted at 30%. Therefore, in the main test the substance was tested up to a maximum concentration of 30%. At 2, 10 and 30% the substance showed SI values of 0.9, 1.1 and 1.3, respectively. Reliable negative and positive controls were included. There was no indication that the test item elicits a SI ≥ 3 when tested up to 30%, and therefore an EC3 value could not be derived. Based on the results of this study, Hyacinth body is not considered to be skin sensitising.
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- 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:
- other: Information derived from analogue
- Justification for type of information:
- The read across justification is presented in the Skin sensitisation Endpoint summary. The accompanying files are also attached there.
- Reason / purpose for cross-reference:
- read-across source
- Positive control results:
- The positive control item, α-Hexylcinnamaldehyde, techical grade, gave a Stimulation Index of greater than 3 when tested at a concentration of 25 % v/v in acetone/olive oil 4:1.
- Key result
- Parameter:
- EC3
- Remarks on result:
- other: EC3 was not reached
- Remarks:
- tested up to 30%, which was the highest tolerable dose, above which systemic effects were seen
- Parameter:
- SI
- Value:
- 0.9
- Remarks on result:
- other: 2%
- Parameter:
- SI
- Value:
- 1.1
- Remarks on result:
- other: 10%
- Parameter:
- SI
- Value:
- 1.3
- Remarks on result:
- other: 30%
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
DETAILS ON STIMULATION INDEX CALCULATION
The SI values calculated for the test item concentrations 2, 10 and 30% were 0.9, 1.1 and 1.3, respectively.
EC3 CALCULATION
There was no indication that the test item elicits a SI ≥ 3 when tested up to 30%, Hyacinth body was not considered to be a skin sensitizer. It was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 30%.
CLINICAL OBSERVATIONS/BODY WEIGHTS:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. - Interpretation of results:
- other: Not sensitising
- Remarks:
- Based on CLP criteria (EC 1272/2008 and its updates)
- Conclusions:
- Skin sensitisation: not sensitising (read-across from Hyacinth body tested in OECD TG 429).
Referenceopen allclose all
Estimation of the Proliferative Response of Lymph Node Cells
Treatment Group |
Concentration |
Stimulation Index |
Result |
Test Item |
2%v/vin |
0.9 |
Negative |
10%v/vin |
1.1 |
Negative |
|
30% v/v in |
1.3 |
Negative |
|
Positive |
25%v/vin |
4.3 |
Positive |
Å = Positive control group served as a common control with Project number 513924.
PRE-SCREEN TEST
Body Weights, Skin Reactions and Clinical Signs
TS1 (%) |
animal |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
||||||||
bw (g)2 |
erythema3 |
erythema |
erythema |
erythema |
erythema |
erythema |
bw (g) |
||||||||
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
30 |
1 |
22.9 |
0 |
0 |
1 |
1P |
1 |
1HP |
0 |
0HP |
0 |
0 |
0 |
0s |
22.8 |
|
2 |
21.2 |
0 |
0 |
1 |
1P |
1 |
1HP |
0 |
0HP |
0 |
0 |
0 |
0s |
21.2 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
100 |
3 |
22.2 |
0 |
1 |
1 |
1 |
1 |
1 |
0 |
1 |
0 |
0 |
0 |
0s |
23.3 |
|
4 |
22.9 |
1 |
1 |
2 |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
24.5 |
Additional pre-screen test: |
|
|
|
|
|
|
|
|
|
|
|
||||
50 |
5 |
22.3 |
1 |
1 |
1 |
1 |
1 |
1P |
1 |
1P |
0 |
1 |
0 |
0 |
22.3 |
|
6 |
20.9 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
19.9 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 TS = test item (% w/w).
2 Body weight (grams).
3 Grading erythema and eschar formation(Left = dorsal surface of left ear; right = dorsal surface of right ear):
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well-defined erythema
s Scaliness
H Hunched posture
P Piloerection
Ear Thickness Measurements
TS1(%) |
Animal |
Day 1 |
Day 3 |
Day 6 |
|||||||
left |
right |
left |
right |
left |
right |
||||||
(mm) |
(mm) |
(mm) |
%2 |
(mm) |
%2 |
(mm) |
%2 |
(mm) |
%2 |
||
|
|
|
|
|
|
|
|
|
|
|
|
30 |
1 |
0.225 |
0.225 |
0.225 |
0 |
0.220 |
-2 |
0.230 |
2 |
0.230 |
2 |
|
2 |
0.230 |
0.230 |
0.230 |
0 |
0.225 |
-2 |
0.240 |
4 |
0.235 |
2 |
|
|
|
|
|
|
|
|
|
|
|
|
100 |
3 |
0.220 |
0.225 |
0.220 |
0 |
0.225 |
0 |
0.240 |
9 |
0.240 |
7 |
|
4 |
0.220 |
0.220 |
0.225 |
2 |
0.225 |
2 |
0.230 |
5 |
0.230 |
5 |
Additional pre-screen test: |
|
|
|||||||||
50 |
5 |
0.225 |
0.220 |
0.235 |
4 |
0.235 |
7 |
0.235 |
4 |
0.235 |
7 |
|
6 |
0.220 |
0.220 |
0.230 |
5 |
0.235 |
7 |
0.240 |
9 |
0.235 |
7 |
|
|
|
|
|
|
|
|
|
|
|
|
Left (mm) = thickness of left ear in millimeters; right (mm) = thickness of right ear in millimeters.
1 TS = test item (% w/w).
2 Percent increase compared to Day 1 pre-dose value.
PRE-SCREEN TEST
At 100%, hunched posture and/or piloerection were noted for both animals between Days 2 and 4. Very slight to well-defined erythema was noted for both animals between Days 1 and 4 and scaliness was noted for animal on Day 6.
At 50%, piloerection was noted for both animals on Days 3 and 4. Very slight erythema was noted for both animals between Days 1 and 6.
At 30%, no signs of systemic toxicity were noted. Very slight erythema was noted for both animals on Days 2 and 3.
Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values for all animals.
Based on the systemic tolerability of the test item, the highest test item concentration selected for the main study was a 30% concentration.
MAIN STUDY
Body Weights and Skin Reactions
group |
TS1 (%) |
animal |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
||||||||
bw (g)2 |
erythema3 |
erythema |
erythema |
erythema |
erythema |
erythema |
bw (g) |
|||||||||
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
|||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 |
0 |
1 |
21.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
20.5 |
|
|
2 |
22.8 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.2 |
|
|
3 |
24.1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.7 |
|
|
4 |
23.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.0 |
|
|
5 |
20.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
20.5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2 |
2 |
6 |
23.2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
21.3 |
|
|
7 |
19.8 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
19.5 |
|
|
8 |
19.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
19.4 |
|
|
9 |
24.7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
24.9 |
|
|
10 |
20.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
21.6 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
10 |
11 |
22.2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.0 |
|
|
12 |
22.9 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.4 |
|
|
13 |
24.0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
25.9 |
|
|
14 |
24.2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.8 |
|
|
15 |
21.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4 |
30 |
16 |
22.0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.6 |
|
|
17 |
21.0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.5 |
|
|
18 |
24.1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.4 |
|
|
19 |
22.6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.2 |
|
|
20 |
22.8 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 TS = test item (% w/w).
2 Body weight (grams).
3 Grading erythema and eschar formation(Left = dorsal surface of left ear; right = dorsal surface of right ear):
0 = No erythema
Individual Disintegrations per Minute and Stimulation Indices Main test:
Treatment Group |
Animal Number |
dpm/ |
Mean dpm/Animal |
Stimulation Indexb |
Result |
Vehicle |
1 |
611 |
725 |
N/A |
N/A |
2 |
745 |
||||
3 |
698 |
||||
4 |
662 |
||||
5 |
911 |
||||
Test Item |
6 |
201 |
635 |
0.9 |
Negative |
7 |
1049 |
||||
8 |
377 |
||||
9 |
1253 |
||||
10 |
296 |
||||
Test Item |
11 |
662 |
780 |
1.1 |
Negative |
12 |
870 |
||||
13 |
855 |
||||
14 |
652 |
||||
15 |
863 |
||||
Test Item 30% v/v in |
16 |
271 |
909 |
1.3 |
Negative |
17 |
1246 |
||||
18 |
940 |
||||
19 |
1365 |
||||
20 |
722 |
||||
Positive Control Item 25% v/v in |
4-1 |
no data |
2566 |
4.3 |
Positive |
4-2 |
no data |
||||
4-3 |
no data |
||||
4-4 |
no data |
||||
4-5 |
no data |
dpm=Disintegrations per minute
N/A= Not applicable
EC3 CALCULATION
There was no indication that the test item elicits a SI ≥ 3 when tested up to 30%, Hyacinth body was not considered to be a skin sensitizer. It was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 30%.
CLINICAL OBSERVATIONS/BODY WEIGHTS:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.
Macroscopic Examination of the Auricular Lymph Nodes and Surrounding Area:
All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals.
Estimation of the Proliferative Response of Lymph Node Cells
Treatment Group |
Concentration |
Stimulation Index |
Result |
Test Item |
2%v/vin |
0.9 |
Negative |
10%v/vin |
1.1 |
Negative |
|
30% v/v in |
1.3 |
Negative |
|
Positive |
25%v/vin |
4.3 |
Positive |
Å = Positive control group served as a common control with Project number 513924.
PRE-SCREEN TEST
Body Weights, Skin Reactions and Clinical Signs
TS1 (%) |
animal |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
||||||||
bw (g)2 |
erythema3 |
erythema |
erythema |
erythema |
erythema |
erythema |
bw (g) |
||||||||
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
30 |
1 |
22.9 |
0 |
0 |
1 |
1P |
1 |
1HP |
0 |
0HP |
0 |
0 |
0 |
0s |
22.8 |
|
2 |
21.2 |
0 |
0 |
1 |
1P |
1 |
1HP |
0 |
0HP |
0 |
0 |
0 |
0s |
21.2 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
100 |
3 |
22.2 |
0 |
1 |
1 |
1 |
1 |
1 |
0 |
1 |
0 |
0 |
0 |
0s |
23.3 |
|
4 |
22.9 |
1 |
1 |
2 |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
24.5 |
Additional pre-screen test: |
|
|
|
|
|
|
|
|
|
|
|
||||
50 |
5 |
22.3 |
1 |
1 |
1 |
1 |
1 |
1P |
1 |
1P |
0 |
1 |
0 |
0 |
22.3 |
|
6 |
20.9 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
19.9 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 TS = test item (% w/w).
2 Body weight (grams).
3 Grading erythema and eschar formation(Left = dorsal surface of left ear; right = dorsal surface of right ear):
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well-defined erythema
s Scaliness
H Hunched posture
P Piloerection
Ear Thickness Measurements
TS1(%) |
Animal |
Day 1 |
Day 3 |
Day 6 |
|||||||
left |
right |
left |
right |
left |
right |
||||||
(mm) |
(mm) |
(mm) |
%2 |
(mm) |
%2 |
(mm) |
%2 |
(mm) |
%2 |
||
|
|
|
|
|
|
|
|
|
|
|
|
30 |
1 |
0.225 |
0.225 |
0.225 |
0 |
0.220 |
-2 |
0.230 |
2 |
0.230 |
2 |
|
2 |
0.230 |
0.230 |
0.230 |
0 |
0.225 |
-2 |
0.240 |
4 |
0.235 |
2 |
|
|
|
|
|
|
|
|
|
|
|
|
100 |
3 |
0.220 |
0.225 |
0.220 |
0 |
0.225 |
0 |
0.240 |
9 |
0.240 |
7 |
|
4 |
0.220 |
0.220 |
0.225 |
2 |
0.225 |
2 |
0.230 |
5 |
0.230 |
5 |
Additional pre-screen test: |
|
|
|||||||||
50 |
5 |
0.225 |
0.220 |
0.235 |
4 |
0.235 |
7 |
0.235 |
4 |
0.235 |
7 |
|
6 |
0.220 |
0.220 |
0.230 |
5 |
0.235 |
7 |
0.240 |
9 |
0.235 |
7 |
|
|
|
|
|
|
|
|
|
|
|
|
Left (mm) = thickness of left ear in millimeters; right (mm) = thickness of right ear in millimeters.
1 TS = test item (% w/w).
2 Percent increase compared to Day 1 pre-dose value.
PRE-SCREEN TEST
At 100%, hunched posture and/or piloerection were noted for both animals between Days 2 and 4. Very slight to well-defined erythema was noted for both animals between Days 1 and 4 and scaliness was noted for animal on Day 6.
At 50%, piloerection was noted for both animals on Days 3 and 4. Very slight erythema was noted for both animals between Days 1 and 6.
At 30%, no signs of systemic toxicity were noted. Very slight erythema was noted for both animals on Days 2 and 3.
Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values for all animals.
Based on the systemic tolerability of the test item, the highest test item concentration selected for the main study was a 30% concentration.
MAIN STUDY
Body Weights and Skin Reactions
group |
TS1 (%) |
animal |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
||||||||
bw (g)2 |
erythema3 |
erythema |
erythema |
erythema |
erythema |
erythema |
bw (g) |
|||||||||
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
|||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 |
0 |
1 |
21.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
20.5 |
|
|
2 |
22.8 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.2 |
|
|
3 |
24.1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.7 |
|
|
4 |
23.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.0 |
|
|
5 |
20.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
20.5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2 |
2 |
6 |
23.2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
21.3 |
|
|
7 |
19.8 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
19.5 |
|
|
8 |
19.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
19.4 |
|
|
9 |
24.7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
24.9 |
|
|
10 |
20.3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
21.6 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3 |
10 |
11 |
22.2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.0 |
|
|
12 |
22.9 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.4 |
|
|
13 |
24.0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
25.9 |
|
|
14 |
24.2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.8 |
|
|
15 |
21.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4 |
30 |
16 |
22.0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.6 |
|
|
17 |
21.0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.5 |
|
|
18 |
24.1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
23.4 |
|
|
19 |
22.6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.2 |
|
|
20 |
22.8 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
22.3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 TS = test item (% w/w).
2 Body weight (grams).
3 Grading erythema and eschar formation(Left = dorsal surface of left ear; right = dorsal surface of right ear):
0 = No erythema
Individual Disintegrations per Minute and Stimulation Indices Main test:
Treatment Group |
Animal Number |
dpm/ |
Mean dpm/Animal |
Stimulation Indexb |
Result |
Vehicle |
1 |
611 |
725 |
N/A |
N/A |
2 |
745 |
||||
3 |
698 |
||||
4 |
662 |
||||
5 |
911 |
||||
Test Item |
6 |
201 |
635 |
0.9 |
Negative |
7 |
1049 |
||||
8 |
377 |
||||
9 |
1253 |
||||
10 |
296 |
||||
Test Item |
11 |
662 |
780 |
1.1 |
Negative |
12 |
870 |
||||
13 |
855 |
||||
14 |
652 |
||||
15 |
863 |
||||
Test Item 30% v/v in |
16 |
271 |
909 |
1.3 |
Negative |
17 |
1246 |
||||
18 |
940 |
||||
19 |
1365 |
||||
20 |
722 |
||||
Positive Control Item 25% v/v in |
4-1 |
no data |
2566 |
4.3 |
Positive |
4-2 |
no data |
||||
4-3 |
no data |
||||
4-4 |
no data |
||||
4-5 |
no data |
dpm=Disintegrations per minute
N/A= Not applicable
EC3 CALCULATION
There was no indication that the test item elicits a SI ≥ 3 when tested up to 30%, Hyacinth body was not considered to be a skin sensitizer. It was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 30%.
CLINICAL OBSERVATIONS/BODY WEIGHTS:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.
Macroscopic Examination of the Auricular Lymph Nodes and Surrounding Area:
All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
The skin sensitization is based on read across from Hyacinth body. First the skin sensitization information on Hyacinth body is presented and thereafter the read across justification is presented. The justification document is also attached in this endpoint summary.
Skin sensitization information on Hyacinth body (CAS# 2556-10-7)
The skin sensitisation potential of Hyacinth body has been tested according to OECD TG 429: Local Lymph Node Assay method. As this is a guideline study performed under GLP conditions, the study was assigned a Klimisch 1 score. In the pre-screen test at 50% piloerection and slight erythema were noted and at 100% piloerection, hunched posture, very slight to well-defined erythema and scaliness were noted. No signs of systemic toxicity were noted at 30%. Therefore, in the main test the substance was tested up to a maximum concentration of 30%. At 2, 10 and 30% the substance showed SI values of 0.9, 1.1 and 1.3, respectively. Reliable negative and positive controls were included. There was no indication that the test item elicits a SI ≥ 3 when tested up to 30%, and therefore an EC3 value could not be derived. Based on the results of this study, Hyacinth body is not considered to be skin sensitising.
Read-across justification
Hyacinth body #3 (CAS no. 7493-57-4, target) and its non-skin sensitizing properties using read across from Hyacinth body (CAS no. 2556-10-7, source)
Introduction and hypothesis for the read across
Hyacinth body #3 has a benzyl ring with an ethyl chain to which an acetal is attached and another propyl chain. For this substance no relevant skin sensitisation data are available which could lead to a decision on this endpoint. Therefore, additional information is used in accordance with Article 13 of REACH where it is said that lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, SARs, grouping and read-across.
Hypothesis: Hyacinth body #3 is expected to have the same skin sensitisation properties as Hyacinth body.
Available experimental information: For the target substance, Hyacinth body #3, the only available animal studiesare two studies which are not following current guidelines. Two reports are available- one from a GPMT test (which used 100% test material) and one from a test performed not according to any guideline. In both tests Hyacinth body #3 did not show any sensitization effects, as well as in the available HRIPT - none of the 42 tested individuals showed any reaction (concentration was not indicated in the report). For the source chemical, Hyacinth body, a well conducted LLNA test (OECD TG 429, GLP, K1) is available, showing the absence of skin sensitisation up to the maximum tested concentration of 30%. This was the highest used concentration because of systemic toxicity occurring at higher concentrations (as evidenced in a preliminary test of this study).
Target and Source chemical(s)
Chemical structures of the target chemical (Hyacinth body #3) and the source chemical (Hyacinth body) are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for skin sensitisation.
Purity / Impurities
Hyacinth body #3 and Hyacinth body are mono-constituents. The impurities in both target and source are all below 2%.
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: Hyacinth body was selected as read across analogue based on analogues found in QSAR Toolbox and RIFM and because it is a substance from IFF portfolio.
Structural similarities and differences: The target chemical Hyacinth body #3 and source chemical Hyacinth body have the same backbone (benzyl ring to which an ethyl and an alkyl chain is attached which is interrupted with the same functional acetal group). The structural difference is that the target Hyacinth body #3 has an additional methyl group compared to Hyacinth body.
Toxicokinetics: Based on the similarity in chemical structure and physico-chemical properties, the target chemical and the source chemical are expected to have comparable toxicokinetics. Both substances are liquid. Their similar molecular weights and logKow suggest a comparable absorption potential. Both acetals, target and source, will follow the same metabolization path with formation of same aldehyde and either 1-propanol (Hyacinth body #3) or ethanol (Hyacinth body).
Toxicodynamics: Reactivity is the key parameter for assessing the skin sensitization potential. The target chemical Hyacinth body #3 and source chemical Hyacinth body are expected to have the same reactivity, based on the fact that both have the same functional acetal group. The fact that the target substance Hyacinth body #3 has one additional methyl group compared to the source substance will not influence this.
Remaining uncertainties: There are no remaining uncertainties based on the reasoning above.
Conclusions for skin sensitisation
When using read across, the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation. For Hyacinth body#3 the skin sensitisation potential can be retrieved from Hyacinth body. The justification is presented in the present document. Hyacinth body#3 is not a skin sensitiser because Hyacinth body is not a skin sensitiser, as tested in an LLNA OECD TG 429.
Final conclusion on hazard: Hyacinth body #3 is not a skin sensitizer.
Data matrix for the read across fromHyacinthbody to Hyacinth body #3
CHEMICAL NAME
Hyacinth body #3
Hyacinth body
Molecular structure
CAS
7493-57-4
2556-10-7
Molecular formula
C13H20O2
C12H18O2
REACH registration
For 2018
For 2018
Einecs
231-327-9
219-868-9
Tanimoto*
1
0.93
Molecular weight
208.30
194.28
Physico-chemical data
Appearance
Liquid
Liquid
Melting point (˚C)
32.27 (C)
<-20 (M)
21.75 (C)
<-20 (M)
Boiling point (˚C)
272.67 (C)
263.4 (M)
255.94 (C)
248.2 (M)
Water solubility at 20˚C (mg/L)
49.14 (C)
86.0 (M)
152.3 (C)
453 (M)
Log Kow
3.40 (C)
4.1 (M)
2.91 (C)
3.5 (M)
Human health
Genetic toxicity
Not mutagenic
Not mutagenic
Skin sensitization animal test
Read across from Hyacinth body
Not sensitizing in LLNA (OECD TG 429)
For testing data, see the IUCLID under the relevant endpoint. Calculated physico-chemical data were generated with EPISuite (version 4.1). C: calculated value, M: measured at IFF.
*Tanimoto calculation:http://chemmine.ucr.edu/similarity/#
Justification for classification or non-classification
Based on the results of the available data from analogue, it is concluded that Hyacinth body #3 does not need to be classified for skin sensitisation in accordance with the criteria outlined in Annex I of CLP (1272/2008/EC) and its updates.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.