4,5-bis(hydroxymethyl)-2-phenyl-1H-imidazole

Endpoint summary

Description of key information

- Skin sensitisation: not a skin sensitizer (OECD 429, GLP, K, Rel.1)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 17 January 2021 to April 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to the OECD TG 429 without any deviation.

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:

July 2012

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

March 2003

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

OECD Principles of Good Laboratory Practice

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in a tightly closed container.
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage: Concentration, stability, and homogeneity of test item formulations were not determined in this study. However, to limit the impact, the test item preparation was performed with approved procedures and documented in detail. Preparations were visually inspected for homogeneity prior to use and all preparations were used within 4 hours after preparation of the formulation.
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis: not reported
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium: The vehicle was chosen from the vehicles specified in the test guideline (in order of preference): Acetone/Olive oil (4:1 v/v), N,N-dimethylformamide, methylethylketone, propylene glycol, dimethylsulfoxide and 1% Pluronic© L92 in Elix water (in case an aqueous vehicle is suitable). The vehicle was selected on the basis of maximizing the solubility based on trial preparations performed at Charles River Den Bosch and on information provided by the Sponsor. Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure. At 50%, none of the vehicles was able to provide a suitable formulation (all were too thick for dosing). At 45% test item, N,N-dimethylformamide provided a homogenous thin paste while Acetone/Olive oil (4:1 v/v), methylethylketone, propylene glycol and dimethylsulfoxide showed a paste that was too thick for dosing. Based on these results, N,N-dimethylformamide was selected as most suitable vehicle for this study
- Reactivity of the test material with the incubation material used (e.g. plastic ware): not reported

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.

Species:

mouse

Strain:

CBA:J

Remarks:

Inbred, SPF-quality

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: unknown
- Age at study initiation: Young adult animals (approximately 10 weeks old) were selected.
- Weight at study initiation: 18.8 to 23.0 g
- Housing: group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized wooden fibers as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: at least 5 days
- Indication of any skin lesions: none reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): target: 18 to 24°C, actual daily mean temperature: 22°C
- Humidity (%): target: 40 to 70%; actual 37-46%. The values that were outside the targeted range occurred for one day and was without a noticeable effect on the clinical condition of the animals or on the outcome of the study.
- Air changes (per hr): ten or greater
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: To:

Vehicle:

dimethylformamide

Concentration:

10%, 5% and 2% w/w. Based on the results of a pre-scree test.

No. of animals per dose:

5

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: 45% was the highest concentration that could be prepared homogeneously.
- Concentration: Initially, two test item concentrations were tested: 25% and 45%. Based on the results of the initially treated animals, two additional animals were treated in a similar manner with two lower concentrations (5% and 10%) at a later stage.
- Irritation: no irritation was observed.
- Systemic toxicity: closed eyes, hunched posture, erected fur, increased respiratory rate and cold to touch were observed at 25% and 45%. At 5% and 10%, no signs of systemic toxicity were noted.
- Ear thickness measurements: Variations in ear thickness during the observation period in all animals were less than 25% from Day 1 pre-dose values.
- Erythema scores: 0 (all animals and all concentrations).
- Other: White staining of test item remnants on the dorsal surface of the ears did not hamper scoring of erythema.

MAIN STUDY:

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response:
SI < 3 - Not a skin sensitizer
SI ≥ 3 - Cat. 1 Skin sensitiser (EC3 value ≤ 2%: sub-category 1A /EC3 value > 2%: sub-category 1B)

TREATMENT PREPARATION AND ADMINISTRATION:
The dosing formulations were prepared daily and dosed within 4 hours after adding the vehicle to the test item.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
No adjustment was made for specific gravity of the vehicle and no correction was made for the purity/composition of the test item, since the test method requires a logical concentration range rather than specific dose levels.

CLINICAL OBSERVATIONS
- Post-dose observations: once daily on Days 1-6 (on Days 1-3 at least 3 hours after dosing)
- Body weights: on Day 1 (pre-dose) and 6 (prior to necropsy).
- Irritation: performed once daily on Days 1-6 (on Days 1-3 within 1 hour after dosing), according to the Draize scale
- Ear thickness measurements: conducted prior to dosing on Days 1 and 3, and on Day 6 using a digital thickness gauge for all animals of each group.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Not required

Positive control results:

The SI values calculated for HCA concentrations 5, 10 and 25% were 1.5, 2.8 and 5.7 respectively. An EC3 value of 12.2% was calculated using linear interpolation.
The calculated EC3 value was found to be in the acceptable range of 4.8 and 19.5%. The results of the 6 monthly HCA reliability checks of the recent years were 12.8, 9.0, 10.9, 8.0, and 13.5%.
Based on the results, it was concluded that the Local Lymph Node Assay as performed at Charles River Den Bosch is an appropriate model for testing for contact hypersensitivity.

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

2%

Key result

Parameter:

SI

Value:

1.7

Test group / Remarks:

5%

Key result

Parameter:

SI

Value:

1.4

Test group / Remarks:

10%

Key result

Parameter:

EC3

Value:

> 10

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 5 and 10% were 506, 736 and 633 DPM, respectively. The mean DPM/animal value for the vehicle control group was 439 DPM.

DETAILS ON STIMULATION INDEX CALCULATION
The individual SI is the ratio of the DPM/animal compared to the DPM/vehicle control group mean
The SI values calculated for the test item concentrations 2, 5 and 10% were 1.2, 1.7 and 1.4, respectively.

EC3 CALCULATION
Since there was no indication that CUREZOL 2PHZ-PW could elicit a SI ≥ 3 when tested up to 10%, it was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 10%.

CLINICAL OBSERVATIONS:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals.

BODY WEIGHTS
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

SIGNS OF TOXICITY (including dermal irritation at the site of administration, if any, e.g. increased ear thickness).
No irritation was observed in any of the animals.
Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values.
White test item remnants were present on the dorsal surface of the ears of all animals at 10% on Days 1-3, which did not hamper scoring of the skin reactions.

MACROSCOPIC EXAMINATION
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.

Table 1           Pre-Screen Test: Body Weights and Skin Reactions

TI ^1(%)	Animal	Day 1			Day 2		Day 3		Day 4		Day 5		Day 6
		bw (g) ^2	Erythema^3		Erythema		Erythema		Erythema		Erythema		Erythema		bw (g)
			left	right	left	right	left	right	left	right	left	right	left	right
25	81	23.2	0f	0f	0f	0f	0f	0f	0	0	0	0	0	0	24.0
	82*	24.7	0f	0f	0f	0f	0f	0f	/	/	/	/	/	/	/
45	83	23.7	0f	0f	0f	0f	0f	0f	0f	0f	0f	0f	0	0	21.9
	84*	23.2	0f	0f	0f	0f	0f	0f	0f	0f	/	/	/	/	/
5	85	22.2	0	0	0	0	0	0	0	0	0	0	0	0	21.8
	86	23.4	0	0	0	0	0	0	0	0	0	0	0	0	23.3
10	87	21.3	0	0	0f	0f	0f	0f	0	0	0	0	0	0	21.6
	88	22.0	0	0	0f	0f	0f	0f	0	0	0	0	0	0	21.7

¹     TI = 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

f     White staining of test item remnants on the dorsal surface of the ears did not hamper scoring of erythema.

*     Animal 82 and 84 were sacrificed for humane reasons on Day 3 and Day 4, respectively. Terminal body weights for animal 82 was 20.3 gram and for animal 84 was 18.5 gram.

/     Not applicable

 

Table 2           Pre-Screen Test: Clinical Signs

 

TI ^1(%)	Animal	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6
25	81	.	g	.	.	.	.
	82*	.	g	grks	/	/	/
45	83	.	g	grk	.	.	.
	84*	.	g	grk	gkrsp	/	/
5	85	.	.	.	.	.	.
	86	.	.	.	.	.	.
10	87	.	.	.	.	.	.
	88	.	.	.	.	.	.

¹     TI = test item (% w/w).

*    Animals 82 and 84 sacrificed for humane reasons on Days 3 and 4, respectively.

.     No clinical signs scored

/     Not applicable

g    Eyes partly closed

r     Erected fur

k    Hunched posture

s     Increased breathing rate

p    Reduced body temperature

 

 Table 3           Pre-Screen Test: Ear Thickness Measurements

TI ^1  (%)	Animal	Day 1		Day 3				Day 6
		Left	Right	Left		Right		Left		Right
		(mm)	(mm)	(mm)	% ^2	(mm)	% ^2	(mm)	% ^2	(mm)	% ^2
25	81	0.210	0.205	0.210	0	0.205	0	0.245	17	0.240	17
	82*	0.220	0.225	0.210	-5	0.215	-4	/	/	/	/
45	83	0.220	0.225	0.230	5	0.225	0	0.230	5	0.230	2
	84*	0.210	0.215	0.215	2	0.225	5	/	/	/	/
Additional pre-screen test:
5	85	0.210	0.210	0.215	2	0.220	5	0.220	5	0.235	12
	86	0.215	0.220	0.215	0	0.220	0	0.230	7	0.230	5
10	87	0.220	0.210	0.220	0	0.215	2	0.230	5	0.230	10
	88	0.205	0.215	0.210	2	0.215	0	0.230	12	0.235	9

Left (mm) = thickness of left ear in millimeters; right (mm) = thickness of right ear in millimeters.

¹     TI = test item (% w/w).

²     Percent increase compared to Day 1 pre-dose value. A 25% value is used as the threshold for selection for

      use in the main study.

*    Animals 82 and 84 sacrificed for humane reasons on Days 3 and 4, respectively.

.     No clinical signs scored

/     Not applicable

 

 

 

Table 4           Main Study: Ear Thickness Measurements

TI ^1  (%)	Animal	Day 1		Day 3				Day 6
		Left	Right	Left		Right		Left		Right
		(mm)	(mm)	(mm)	% ^2	(mm)	% ^2	(mm)	% ^2	(mm)	% ^2
0	1	0.220	0.220	0.220	0	0.220	0	0.215	-2	0.220	0
	2	0.215	0.210	0.210	-2	0.215	2	0.220	2	0.225	7
	3	0.190	0.210	0.200	5	0.215	2	0.225	18	0.230	10
	4	0.200	0.205	0.210	5	0.205	0	0.230	15	0.235	15
	5	0.220	0.215	0.215	-2	0.220	2	0.220	0	0.225	5
2	6	0.215	0.220	0.220	2	0.225	2	0.240	12	0.245	11
	7	0.220	0.220	0.225	2	0.220	0	0.235	7	0.230	5
	8	0.210	0.215	0.215	2	0.225	5	0.220	5	0.230	7
	9	0.215	0.205	0.220	2	0.215	5	0.220	2	0.220	7
	10	0.215	0.220	0.220	2	0.225	2	0.240	12	0.245	11
5	11	0.210	0.220	0.220	5	0.225	2	0.235	12	0.240	9
	12	0.205	0.210	0.215	5	0.220	5	0.240	17	0.250	19
	13	0.230	0.225	0.235	2	0.230	2	0.235	2	0.230	2
	14	0.220	0.215	0.220	0	0.220	2	0.240	9	0.235	9
	15	0.205	0.220	0.215	5	0.230	5	0.230	12	0.240	9
10	16	0.215	0.220	0.225	5	0.235	7	0.230	7	0.240	9
	17	0.200	0.210	0.220	10	0.225	7	0.220	10	0.225	7
	18	0.210	0.215	0.225	7	0.230	7	0.240	14	0.245	14
	19	0.225	0.230	0.235	4	0.240	4	0.235	4	0.240	4
	20	0.210	0.205	0.220	5	0.225	10	0.225	7	0.230	12

Left (mm) = thickness of left ear in millimeters; right (mm) = thickness of right ear in millimeters.

¹   TI = test item (% w/w).

²   Percent increase compared to Day 1 pre-dose value. A 25% value is used as the threshold for selection for

    use in the main study.

 

 

 

Table 5           Main Study: Body Weights and Skin Reactions

Group	TI ^1(%)	Animal	Day 1			Day 2		Day 3		Day 4		Day 5		Day 6
			bw (g) ^2	Erythema^3		Erythema		Erythema		Erythema		Erythema		Erythema		bw (g)
				left	right	left	right	left	right	left	right	left	right	left	right
1	0	1	20.3	0	0	0	0	0	0	0	0	0	0	0	0	20.5
		2	22.6	0	0	0	0	0	0	0	0	0	0	0	0	21.8
		3	21.7	0	0	0	0	0	0	0	0	0	0	0	0	22.3
		4	23.0	0	0	0	0	0	0	0	0	0	0	0	0	22.9
		5	21.6	0	0	0	0	0	0	0	0	0	0	0	0	22.3
2	2	6	20.9	0	0	0	0	0	0	0	0	0	0	0	0	21.9
		7	21.0	0	0	0	0	0	0	0	0	0	0	0	0	22.2
		8	21.0	0	0	0	0	0	0	0	0	0	0	0	0	21.6
		9	18.8	0	0	0	0	0	0	0	0	0	0	0	0	19.7
		10	21.9	0	0	0	0	0	0	0	0	0	0	0	0	22.7
3	5	11	19.9	0	0	0	0	0	0	0	0	0	0	0	0	22.5
		12	20.2	0	0	0	0	0	0	0	0	0	0	0	0	22.2
		13	20.7	0	0	0	0	0	0	0	0	0	0	0	0	21.7
		14	20.3	0	0	0	0	0	0	0	0	0	0	0	0	21.4
		15	21.0	0	0	0	0	0	0	0	0	0	0	0	0	21.5
4	10	16	21.9	0f	0f	0f	0f	0f	0f	0	0	0	0	0	0	22.1
		17	19.9	0f	0f	0f	0f	0f	0f	0	0	0	0	0	0	20.8
		18	19.5	0f	0f	0f	0f	0f	0f	0	0	0	0	0	0	20.9
		19	21.3	0f	0f	0f	0f	0f	0f	0	0	0	0	0	0	21.9
		20	21.4	0f	0f	0f	0f	0f	0f	0	0	0	0	0	0	20.6

¹   TI = 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

f   White staining of test item remnants on the dorsal surface of the ears did not hamper scoring for erythema.

 

 

Table 6           Main Study: Relative Size Lymph Nodes, Radioactivity Counts (DPM) and Stimulation Index (SI)

Group	TI ^1(%)	Animal	Size Nodes ^2		DPM ^3 / Animal	Mean DPM ± SEM ^4			Mean SI ± SEM
			left	right
1	0	1	n	n	252	439	±	69	1.0	±	0.2
		2	n	n	325
		3	n	n	584
		4	n	n	602
		5	n	n	430
2	2	6	n	n	556	506	±	20	1.2	±	0.0
		7	n	n	477
		8	n	n	446
		9	n	n	530
		10	n	n	521
3	5	11	n	n	663	736	±	87	1.7	±	0.2
		12	n	n	955
		13	n	n	509
		14	n	n	633
		15	n	n	922
4	10	16	n	n	436	633	±	76	1.4	±	0.2
		17	n	n	827
		18	n	n	756
		19	n	n	666
		20	n	n	479

¹   TI = test item (% w/w).

²   Relative size auricular lymph nodes (-, -- or ---: degree of reduction, +,++ or +++: degree of enlargement, n: considered to be normal).

³    DPM = Disintegrations per minute.

⁴    SEM = Standard Error of the Mean.

Interpretation of results:

GHS criteria not met

Conclusions:

Since there was no indication that CUREZOL 2PHZ-PW could elicit a SI ≥ 3 when tested up to 10%, it was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 10%.

Executive summary:

In a dermal sensitization study with the test item in N,N-dimethylformamide, young adult CBA/J strain female (5/concentration) were tested using the Local Lymph Node Assay.

The study was carried out based on the guidelines described in:

• OECD Guideline 429. Skin Sensitization: Local Lymph Node Assay, July 2010.


• EC No 640/2012 Part B. Skin Sensitization: Local Lymph Node Assay, July 2012.


• EPA Health Effects Test Guideline OPPTS 870.2600. Skin Sensitization, March 2003.

 

The six-month reliability check with Alpha-Hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at Charles River Den Bosch is an appropriate model for testing for contact hypersensitivity.

 

Test item concentrations selected for the main study were based on the results of a pre-screen test. At 25 and 45% (maximum possible concentration), clinical signs of systemic toxicity were noted and therefore these concentrations did not meet the selection criteria. In addition, one animal at 25% and one at 45% were sacrificed for humane reasons on Days 3 or 4. At 5% and 10%, no signs of systemic toxicity were noted and no irritation was observed. Therefore, 10% was selected as highest concentration for the main study.

In the main study, three experimental groups of five female CBA/J mice were treated with test item concentrations of 2, 5 or 10% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone
(N,N-dimethylformamide). Three days after the last exposure, all animals were injected with ³H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

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.

Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 5 and 10% were 506, 736 and 633 DPM, respectively. The mean DPM/animal value for the vehicle control group was 439 DPM. The SI values calculated for the test item concentrations 2, 5 and 10% were 1.2, 1.7 and 1.4, respectively.

Since there was no indication that CUREZOL 2PHZ-PW could elicit a SI ≥ 3 when tested up to 10%, it was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 10%.

 

Under the test conditions, the test item does not have to be classified according to the regulation (EC) No. 1272/ 2008 (CLP) and to the Globally Harmonized System of classification and labelling of chemicals (GHS).

 

This study is acceptable and satisfies the requirements for skin sensitisation testing (OECD 429) in mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a dermal sensitization study with the test item in N,N-dimethylformamide, young adult CBA/J strain female (5/concentration) were tested using the Local Lymph Node Assay.

The study was carried out based on the guidelines described in:

• OECD Guideline 429. Skin Sensitization: Local Lymph Node Assay, July 2010.


• EC No 640/2012 Part B. Skin Sensitization: Local Lymph Node Assay, July 2012.


• EPA Health Effects Test Guideline OPPTS 870.2600. Skin Sensitization, March 2003.

 

The six-month reliability check with Alpha-Hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at Charles River Den Bosch is an appropriate model for testing for contact hypersensitivity.

 

Test item concentrations selected for the main study were based on the results of a pre-screen test. At 25 and 45% (maximum possible concentration), clinical signs of systemic toxicity were noted and therefore these concentrations did not meet the selection criteria. In addition, one animal at 25% and one at 45% were sacrificed for humane reasons on Days 3 or 4. At 5% and 10%, no signs of systemic toxicity were noted and no irritation was observed. Therefore, 10% was selected as highest concentration for the main study.

In the main study, three experimental groups of five female CBA/J mice were treated with test item concentrations of 2, 5 or 10% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone
(N,N-dimethylformamide). Three days after the last exposure, all animals were injected with ³H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

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.

Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 5 and 10% were 506, 736 and 633 DPM, respectively. The mean DPM/animal value for the vehicle control group was 439 DPM. The SI values calculated for the test item concentrations 2, 5 and 10% were 1.2, 1.7 and 1.4, respectively.

Since there was no indication that CUREZOL 2PHZ-PW could elicit a SI ≥ 3 when tested up to 10%, it was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 10%.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Harmonised classification: 

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

 

Self classification: 

Based on the available information no additional self-classification is proposed according to the CLP and the GHS.

No information is available regarding respiratory sensitisation.