Batilol

Endpoint summary

Description of key information

A theorical AOP (adverse outcome pathway) approach was considered on the test substance but shows its limits when it comes to complexe substances:

The substance is a monoconstituant with LogPow of 7.8 and water solubility of 4.26 x 10-3 mg.L-1 (25°C).

 

-the key event n°1, DPRA test (OECD 442C) was unrealizable due to the fact that the substance is insoluble in all the vehicles possibly used for this test (acetonitrile, water, 1:1mixture of both, isopropanol, 1:1 mixture of acetone:acetonitrile; acetone; 1:9mixture of DMSO:acetonitrile; 1:1 mixture of DMSO:acetonitrile).

 

-the key event n°2, Keratinosens test (OECD guideline 442D) was unrealizable because substances with a log P>7 fall out of the applicability domain of the assay and cannot be tested.

 

-the key event n°3, Hclat test (OECD 442E) was unrealizable because log Kow>3.5. Other guidelines assessing this key event are emerging. In particular the GARD test, by the Senzagen laboratory that we found realizable on the test substance Batilol. This method is currently being validated by ECVAM and was already accepted by ECHA in the registration dossiers. Therefore, this test was performed on the substance Batilol and concluded that this substance isn’t a skin sensitizer.

 

No other test with other key event was available. The AOP approach can’t be concluded.

It was then decided to use literature data to complete the results of the GARD test.

 

Batilol is a substance used in cosmetics to reduce inflammation. The publication anti-inflammatory effect of alkyl glyceryl ethers on the skin, Satoko Kaburagi and its colleagues shows that this is an anti-inflammatory substance.

A CIR (Cosmetic Ingredient Review) report was available on the family Alkyl glyceryl ethers. The CIR Expert Panel concluded that use of alkyl glyceryl ethers in cosmetic ingredients is safe, -especially since these substances are not sensitizing - in the present practices of use and concentration described in the safety assessment.

 

Those combined information allow us to expect that the substance Batilol is not a skin sensitizer.

 

Please see report in 13.2 for more information.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Genomic Allergen Rapid Detection (GARDTM)

Version / remarks:

currently under ECVAM validation.

Principles of method if other than guideline:

please see documentation attached regarding GARD skin test.
It is a new test currently under validation with ECVAM/OECD.
Genomic Allergen Rapid Detection (GARDTM) is an in vitro assay designed to predict the ability of chemical substances to induce skin sensitisation based on the analysis of the relative expression levels of a biomarker signature of 196 genes using a human myeloid leukemia cell line called SenzaCell. The GARDTM is based on chemical stimulation of the SenzaCell line, acting as an in vitro model of human Dendritic Cells (DCs). The readout of the assay is a transcriptional quantification of the genomic predictors, collectively termed the GARDTM Prediction Signature (GPS), using Nanostring nCounter technology.

GLP compliance:

yes (incl. QA statement)

Type of study:

activation of dendritic cells

Specific details on test material used for the study:

Batch No.: 8462
Purity: approx. 99 %
Physical State: solid (powder)
Colour: white to pale yellow
Stability: stable
Storage Conditions: room temperature, protected from light
Expiry Date: 10.07.2021
Safety Precautions: The routine hygienic procedures will be sufficient to assure personnel health and safety.

Details on the study design:

Preparation of the test item:
the test item is dissolved in either dimethyl sulfoxide (DMSO), water or in a different suitable solvent

Test system:
FACS:
FACS: BD Canto II
Software: BD FACS DIVA 6.0
Voltage Settings: FSC: 129 V, SSC: 435 V, FITC: 290 V, PE/PI: 315 V
Threshold value of FSC: 5000
Compensation: PI – 21.09 % FITC, FITC – 1.41 % PI

Cell line:
Human myeloid leukemia cell line Senza cells, provided by SenzaGen AB.
Cells tested routinely for mycoplasma, were seeded in culture medium at an appropriate density and sub-cultured at least 2 weeks before the test.
Only cells at a low passage number (<16) were used.
Cells are cultured in 175cm2 culture flasks (Greiner) in MEM/Alpha Modification with L-glut, Ribo-Deoxyribo (Thermo Scientific; Cat. No.: SH30265.01) supplemented with 20% fetal bovine serum (FBS, Gibco Life Science, Cat No.: 10270-106) (= semi-complete medium), and freshly added 40 ng/mL GM-CSF (Miltenyi Biotec, Cat No.: 130-093-868) in a humidified incubator at 37 ± 1°C and 5% CO2 (complete medium).

Dose groups:
Medium Control: semi-complete medium
Solvent Control: 0.1% (v/v) for DMSO or a different solvent for the test item and the positive control
Positive Control: 75 μM p-Phenylenediamine (CAS : 106-50-3)
Test Item:
Input finder: 9 concentrations of the test item down to 1 mM stock solution
Main stimulation: 1 concentration, which will lead to a cell viability of 90 ± 5%

Experimental procedure:
pre-test:
Nine concentrations (stock solutions) down to 1 mM were prepared. (i.e. 500 mM – 400 mM – 300 mM – 200 mM – 100 mM – 50 mM – 10 mM – 5 mM – 1 mM). These stock solutions were further diluted 100-fold into semi-complete medium giving the stock B solutions.
Highest concentration tested: 500µM.

Main test:
A stock solution of the positive control (75 mM) in DMSO and a stock solution 1000-fold higher as the GARD input concentration of the test item in the solvent determined in the solvent finding pre-experiment were freshly prepared immediately before use.
The stock solution of the positive control, pure DMSO as a negative control, the stock solution of the test item and the solvent of the test item were diluted 100-fold into semi-complete medium (= Stock B) to achieve the in-well concentration of 0.1% DMSO.
For testing, SenzaCells were pre-cultured for at least 72 h - 96 h in culture flasks at a cell density of 0.2 x 10^6 cells/mL. Prior to test item application, cells were harvested from the cell culture flask by centrifugation and were re-suspended in fresh semi-complete medium at a density of 2.22 x 10^5 cell/mL. Then 3.6 mL of cell suspension were seeded into a 12 well plate-bottom plate (2 x 10^5 cells/well).
The stock B solutions of the positive control, the solvent control of the test item input concentration and the solvent of the test item were mixed 1:10 (v/v) with the cell suspension prepared in the 12-well plate. Treated plates were incubated for 24 h ± 0.5 h at 37 °C ± 1 °C and 5% ± 0.5% CO2.
The cells were stained to check the quality of the cells.

After 24 h ± 0.5 h of exposure, 1 mL of the cells were transferred three times into small reaction tubes and further 500 μL were transferred twice into two FACS tubes. The cells of the reaction tubes were collected by centrifugation (approx. 300 x g), re-suspended in 500 μL TRIzol and frozen at < -20 °C. The cells of the FACS tubes were washed twice with FACS buffer. After washing, cells were re-suspended in 50 μL propidium iodide (PI) solution (1 μg/mL) in FACS buffer. Cells were stained for approx. 10 minutes at 2-8 °C in the dark. After staining, cells were washed with FACS buffer again and will be re-suspended in 200 μL FACS buffer.
The PI uptake of the cells (as an indicator of cytotoxicity) was analysed immediately after the staining procedure by flow cytometry using an excitation wavelength of λ = 488 nm and an emission wavelength of λ > 650 nm. A total of 10.000 living (PI negative) cells were acquired and cell viability will be calculated for each sample according to the following equation:
Rv = (Vs/Vc)X100
where: Rv = Relative viability of the sample in %
Vs = Absolute viability of the sample in %
Vc = Absolute viability of the mean of the two unstimulated control samples in %

RNA isolation:
The first tube of each TRIzol sample triplicates was thawed slowly on ice. The samples were centrifuged to remove particulate debris and the supernatant was transferred into new tubes. An equal volume of 95% - 100% ethanol was added and the whole mixture was transferred on the column of a Zymo-SpinTM IIC Columns (ZymoResearch Cat.R5052).
The flow through was discarded and the column was washed twice with 400 μL with the Direct-zolTM RNA PreWash. The flow through was discarded again. After the pre-washing step the column was washed with 700 μL RNA wash buffer. The flow through was discarded again and the column was placed in a new RNAse-free tube. The RNA was eluted with 25 μL RNAse-free water. After centrifugation the collected RNA was transferred on the column again to elute the whole RNA. The RNA was stored at -80 °C for shipment.


Endpoint Measurement (at Test Side 1)

1/RNA Quality Control
The RNA quality and quantity was measured with an Agilent 2100 BioAnalyser. If the RNA sample did not pass the quality control criteria (see section 11.3) the RNA had to be isolated from the last two TRIzol samples and quality had to be measured again.
RNA samples which had passed the criteria undergo Nanostring endpoint measurement with an appropriate code set for GARD skin.

2/ Nanostring Hybridisation
All hybridization samples were use a total RNA concentration of 100 ng.
All RNA samples were diluted to 20 ng/μL with RNA-free water to use 5 μL of each for hybridization.
For hybridization mix 8 μL of the master mix (provided in the Nanostring master kit), 5 μL RNA sample (20 ng/μL) and 2 μL of the capture code set were mixed. The whole approach was incubated in a thermocycler at 65 °C for 24 h ± 0.5 h.

3/ Setting up the Nanostring Preparation and Measurement
The nCounter Prepstation (Nanostring) was prepared as described in the manual. After hybridization the samples were removed from the thermocycler and spinned down before opening. The samples were placed in the nCounter Prepstation, too. The preparation of the nanostring cartridges took around 3 hours.
The cartridges were analysed by an nCounter Digital Analyser (Nanostring).

Key result

Run / experiment:

mean

Parameter:

other: Mean decision value

Value:

-1.2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

All the acceptance criteria are met for the BioAnalyser and Nanostring measurement.

Prediction for skin sensitization:

The prediction is defined as described below:

-      If the mean decision value (DV) of biological replicate samples is ≥0, the substance is classified as a sensitizer

If the mean decision value (DV) of biological replicate samples is <0, the substance is classified as anon-sensitizer

Results table:

Negative Control		Positive Control		BATILOL
Decision Values	Main Stimulation	Decision Values	Main Stimulation	Decision Values
-1.57	1	10.17	1	-0.97
-1.56	2	9.37	2	-1.35
-1.99	3	9.1	3	-1.28
-1.71	Mean	9.55	Mean	-1.20
Predicition
negative		positive		negative

Interpretation of results:

GHS criteria not met

Executive summary:

The sensitization potential of the test substance was performed according to the GARD assay (It is a new test currently under validation with ECVAM/OECD). Genomic Allergen Rapid Detection (GARDTM) is an in vitro assay designed to predict the ability of chemical substances to induce skin sensitisation based on the analysis of the relative expression levels of a biomarker signature of 196 genes using a human myeloid leukemia cell line called SenzaCell. The GARDTM is based on chemical stimulation of the SenzaCell line, acting as an in vitro model of human Dendritic Cells (DCs). The readout of the assay is a transcriptional quantification of the genomic predictors, collectively termed the GARDTM Prediction Signature (GPS), using Nanostring nCounter technology.)

In this study under the given conditions the test item did not change the genomic profile of the cells for sensitisation in at least three independent experiment runs. Therefore, the test item might be considered as non-sensitiser.

Reference 2

Endpoint:

skin sensitisation, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2011

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data from a CIR report on Batilol's family's safety (One maximization test (OECD 406) - this endpoint study report, One LLNA test - see endpoint study report "skin sensitization.WoE2", Human data: four RIPT test - see endpoint study report "skin sensitization.WoE2)" and from a publication on the non-inflammatory properties of batilol (see endpoint study report "skin sensitization.WoE4)" . Data sources all agree in the presumed non-sensitizer potential of the substance Batilol and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

In the CIR report, the safety of use of the family of alkyl glyceryl ethers (which include batilol) was assessed with different validated literature data.

GLP compliance:

not specified

Type of study:

other: Several tests mentionned in the CIR report.

Justification for non-LLNA method:

Data were taken from the CIR (cosmetic ingredient review) report, which has been published by experts that selected relevant data. Data that were used in this report:
One maximization test (OECD 406).
One LLNA test. (see endpoint study report "skin sensitization.WoE2")
Human data: one RIPT test. (see endpoint study report "skin sensitization.WoE3")

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

2 groups of 20 guinea pigs (10 males, 10 females/group)

Key result

Group:

test chemical

Dose level:

Induction phase: 0.5%, challenge phase: 50%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no sensitization was observed in any of the animals observed

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Executive summary:

The safety of alkyl glyceryl ethers as cosmetic ingredients was assessed by the CIR (Cosmetic Ingredient Review), a USA committee of experts. Batilol is part of this family. Data are available on the substance ethylhexylglycerin, which is an analogue of the batilol, and is broadly used in cosmetic products.

 

Animal data:

In a maximization test (OECD TG 406 test method), the skin sensitization potential ofethylhexylglycerin(Sensiva® SC 50) was evaluated using 2 groups of 20 guinea pigs (10 males, 10 females/group); one of the 2 groups served as the negative control. The induction phase involved 10 test animals with 3 pairs of injection sites on the shaved neck according to the following procedure. Starting at day 0, 0.1 ml of the test substance was injected intradermally into the neck region (2 pairs of injection sites) at concentrations of 0.5% in peanut oil and 0.5% in Freund’s complete adjuvant/saline 1:1, respectively. The third pair of sites was injected with Freund’s complete adjuvant/water 1:1. On day 7, the undiluted test substance was applied (under occlusive dressing) to the neck for 48 h. On day 21, the animals were challenged with the test substance (50% in peanut oil, under occlusive dressing) for 24 or 48 h. Sensitization was not observed in any of the animals tested.

 

The sensitization potential of ethylhexylglycerin (Sensiva® SC 50) was evaluated in the local lymph node assay at concentrations up to 50%. The test substance did not induce 3-fold increases (EC3-value) in tritiated thymidine (3HTdR) incorporation at any concentration tested, and it was concluded that Ethylhexylglycerin was not a sensitizer.

 

Human data:

Products containing ethylhexylglycerin at concentrations ranging from 0.4% to ~ 1% were neither skin irritants nor sensitizers in RIPT’s involving human subjects. Positive patch test results were reported for dermatitis patients patch tested with ethylhexylglycerin at concentrations up to 10%. However results were negative for control subjects.

 (see endpoint study record "skin sensitization.WoE4" for more information).

The CIR Expert Panel concluded that use of alkyl glyceryl ethers in cosmetic ingredients is safe in the present practices of use and concentration described in the safety assessment.

Reference 3

Endpoint:

skin sensitisation, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2011

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data from a CIR report on Batilol's family's safety (One maximization test (OECD 406)- see endpoint study report "skin sensitization.WoE1", One LLNA test - this endpoint study report, Human data: four RIPT test - see endpoint study report "skin sensitization.WoE2)" and from a publication on the non-inflammatory properties of batilol (see endpoint study report "skin sensitization.WoE4)" . Data sources all agree in the presumed non-sensitizer potential of the substance Batilol and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Principles of method if other than guideline:

In the CIR report, the safety of use of the family of alkyl glyceryl ethers (which include batilol) was assessed with different validated literature data.

GLP compliance:

not specified

Remarks:

Quality check QLT016: GLP compliance set to "not specifieid" because this is literature data.

Type of study:

other: Several tests mentionned in the CIR report.

Justification for non-LLNA method:

Data were taken from the CIR (cosmetic ingredient review) report, which has been published by experts that selected relevant data. Data that were used in this report:
One maximization test (OECD 406). (see endpoint study report "skin sensitization.WoE1")
One LLNA test.
Human data: four RIPT test. (see endpoint study report "skin sensitization.WoE3")

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

not available

Key result

Remarks on result:

not measured/tested

Remarks:

the precise value is not available in the CIR report. However, it was concluded that substance isn't a skin sensitizer at up to 50%.

Interpretation of results:

GHS criteria not met

Executive summary:

The safety of alkyl glyceryl ethers as cosmetic ingredients was assessed by the CIR (Cosmetic Ingredient Review), a USA committee of experts. Batilol is part of this family. Data are available on the substance ethylhexylglycerin, which is an analogue of the batilol, and is broadly used in cosmetic products.

 

Animal data:

In a maximization test (OECD TG 406 test method), the skin sensitization potential ofethylhexylglycerin(Sensiva® SC 50) was evaluated using 2 groups of 20 guinea pigs (10 males, 10 females/group); one of the 2 groups served as the negative control. The induction phase involved 10 test animals with 3 pairs of injection sites on the shaved neck according to the following procedure. Starting at day 0, 0.1 ml of the test substance was injected intradermally into the neck region (2 pairs of injection sites) at concentrations of 0.5% in peanut oil and 0.5% in Freund’s complete adjuvant/saline 1:1, respectively. The third pair of sites was injected with Freund’s complete adjuvant/water 1:1. On day 7, the undiluted test substance was applied (under occlusive dressing) to the neck for 48 h. On day 21, the animals were challenged with the test substance (50% in peanut oil, under occlusive dressing) for 24 or 48 h. Sensitization was not observed in any of the animals tested.

 

The sensitization potential of ethylhexylglycerin (Sensiva® SC 50) was evaluated in the local lymph node assay at concentrations up to 50%. The test substance did not induce 3-fold increases (EC3-value) in tritiated thymidine (3HTdR) incorporation at any concentration tested, and it was concluded that Ethylhexylglycerin was not a sensitizer.

 

Human data:

Products containing ethylhexylglycerin at concentrations ranging from 0.4% to ~ 1% were neither skin irritants nor sensitizers in RIPT’s involving human subjects. Positive patch test results were reported for dermatitis patients patch tested with ethylhexylglycerin at concentrations up to 10%. However results were negative for control subjects.

  (see endpoint study record "skin sensitization.WoE4" for more information).

The CIR Expert Panel concluded that use of alkyl glyceryl ethers in cosmetic ingredients is safe in the present practices of use and concentration described in the safety assessment.

Reference 4

Endpoint:

skin sensitisation, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2011

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data from a CIR report on Batilol's family's safety (One maximization test (OECD 406)- see endpoint study report "skin sensitization.WoE1", One LLNA test - see endpoint study report "skin sensitization.WoE2", Human data: four RIPT test - this endpoint study report) and from a publication on the non-inflammatory properties of batilol (see endpoint study report "skin sensitization.WoE4)" . Data sources all agree in the presumed non-sensitizer potential of the substance Batilol and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

according to guideline

Guideline:

other: RIPT (repeated insult patch test) on human subjects

Principles of method if other than guideline:

In the CIR report, the safety of use of the family of alkyl glyceryl ethers (which include batilol) was assessed with different validated literature data.

GLP compliance:

not specified

Remarks:

Quality check QLT016: GLP compliance set to "not specifieid" because this is literature data.

Type of study:

other: Several tests mentionned in the CIR report.

Justification for non-LLNA method:

Data were taken from the CIR (cosmetic ingredient review) report, which has been published by experts that selected relevant data. Data that were used in this report:
One maximization test (OECD 406). (see endpoint study report "skin sensitization.WoE1")
One LLNA test. (see endpoint study report "skin sensitization.WoE2")
Human data: four RIPT test.

Key result

Group:

test chemical

Dose level:

0.4% to ~ 1%

No. with + reactions:

0

Total no. in group:

1 042

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Executive summary:

The safety of alkyl glyceryl ethers as cosmetic ingredients was assessed by the CIR (Cosmetic Ingredient Review), a USA committee of experts. Batilol is part of this family. Data are available on the substance ethylhexylglycerin, which is an analogue of the batilol, and is broadly used in cosmetic products.

 

Animal data:

See endpoint study record "skin sensitization.WoE1" and skin sensitization.WoE2".

 

Human data:

Products containing ethylhexylglycerin at concentrations ranging from 0.4% to ~ 1% were neither skin irritants nor sensitizers in RIPT’s involving human subjects (1042 subjects in total). Positive patch test results were reported for dermatitis patients patch tested with ethylhexylglycerin at concentrations up to 10%. However results were negative for control subjects.

This substance was therefore considered as non sensitizer.

The skin irritation and sensitization potential of a facial cream containing 0.4975% ethylhexylglycerin was evaluated in an RIPT using 600 subjects (ages not stated). Occlusive patches (0.5" x 0.5") containing the test substance were applied (48 h) weekly for a total of 10 induction applications. Reactions were scored after patch removal. After a 2-week nontreatment period, challenge patches were applied for 48 h. As second challenge application (48 h) was made one week later. There was no evidence of primary irritation, skin fatiguing, or allergic eczematous dermatitis.

A foundation containing 0.4% ethylhexylglycerin was evaluated for skin irritation and sensitization potential in an RIPT involving 108 male and female (18 to 70 years old).

Partially-occlusive patches (2 cm x 2 cm) containing the test substance (~ 150 mg) were applied for 24 h, for a total of 9 induction applications. During the challenge phase (105 subjects), test sites were scored at the time of patch removal and 24 h and 48 h later. The induction application site and a new test site were challenged. The foundation was neither a skin irritant nor sensitizer.

A repeated insult patch test (RIPT) on a liquid eyeliner containing 0.5% ethylhexylglycerin was performed using 115 male and female subjects (16 to 79 years old). Approximately 0.2 g of the test substance on a 1" x 1" semi-occlusive patch was applied (24 h) 3 times per week for a total of 9 induction applications. Reactions were scored after patch removal. After a 2-week non-treatment period, a challenge patch was applied to a new site adjacent to the original induction site. Challenge reactions were scored at 24 h and 72 h post-application. The product did not have skin irritation or allergic contact sensitization potential.

The skin irritation and sensitization potential of a makeup preparation containing 0.995% ethylhexylglycerin was studied in 111 male and female subjects (18 to 70 years old ) using the same test procedure, except for the application of 100 µl of test material to the partially-occlusive patch. The number of subjects who participated in the challenge phase was 108. The makeup preparation was neither a skin irritant nor sensitizer.

An RIPT on a fragranced body lotion containing 0.6965% ethylhexylglycerin was conducted using 108 subjects (between 18 and 70 years old).41 A semi-occlusive patch containing the test substance was applied (24 h) 3 times per week for a total of 9 induction applications. Reactions were scored after patch removal. After a 2-week non-treatment period, a challenge patch was applied to a previously untreated site for 24 h. Reactions were scored at 24 h, 48 h, and 72 h. The body lotion was not a skin irritant or sensitizer.

 

The CIR Expert Panel concluded that use of alkyl glyceryl ethers in cosmetic ingredients is safe, -especially since these substances are not sensitizing - in the present practices of use and concentration described in the safety assessment.

Reference 5

Endpoint:

skin sensitisation, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2005

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data from a CIR report on Batilol's family's safety (One maximization test (OECD 406)- see endpoint study report "skin sensitization.WoE1", One LLNA test - see endpoint study report "skin sensitization.WoE2", Human data: four RIPT test - see endpoint study report "skin sensitization.WoE2)" and from a publication on the non-inflammatory properties of batilol (this endpoint study report)" . Data sources all agree in the presumed non-sensitizer potential of the substance Batilol and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

no guideline followed

Principles of method if other than guideline:

In the publication ANTI-INFLAMMATORY EFFECT OF ALKYL GLYCERYL ETHERS ON THE SKIN, Satoko Kaburagi and its colleagues assessed the anti-inflammatory effect of the batilol.
The effects of batyl alcohol on the secretion of pro-inflammatory substances (IL-1a and PGE2) from UVB-irradiated keratinocytes, and the suppression of UVB-induced intracellular peroxide elevation to analyze its precise mechanism of action were examined.

GLP compliance:

not specified

Type of study:

other: publication, assessing anti-inflammatory effects of the batilol

Key result

Remarks on result:

no indication of skin sensitisation

Remarks:

To analyze the anti-inflammatory pathway of batyl alcohol, its effect on the secretion of pro-inflammatory substances (IL-1a and PGE2) from NHKs following UVB irradiation were examined. UVB irradiation significantly increased IL-1a and PGE2 secretion compared with sham irradiated cells. Batyl alcohol significantly suppressed the secretion of both pro-inflammatory substances (IL-1a and PGE2) elevated by UVB irradiation, but had no effect on their secretion under the sham-irradiation condition. The results indicate that batyl alcohol suppresses the secretion of pro-inflammatory substances which are elevated by UVB irradiation.

Interpretation of results:

GHS criteria not met

Executive summary:

In the publication ANTI-INFLAMMATORY EFFECT OF ALKYL GLYCERYL ETHERS ON THE SKIN, Satoko Kaburagi and its colleagues assessed the anti-inflammatory effect of the batilol.

The effects of batyl alcohol on the secretion of pro-inflammatory substances (IL-1a and PGE2) from UVB-irradiated keratinocytes, and the suppression of UVB-induced intracellular peroxide elevation to analyze its precise mechanism of action were examined.

ln an in vitro study, batyl alcohol reduced the secretion of pro-inflammatory substances, IL-1a and PGE2, from UVB-irradiated keratinocytes. Since it has been well established that the secretion of IL-1a and PGE2 are stimulated by ROS, we examined the potential of batyl alcohol for ROS scavenging. However, batyl alcohol did not show any reduction of intracellular peroxide elevation following UVB irradiation. This result suggests that the suppressive effects of batyl alcohol on the secretion of pro-inflammatory substances does not result from the removal of ROS. Although the signal(s) of batyl alcohol resulting in its anti-inflammatory effect has not been identified, this is the first report demonstrating the anti-inflammatory effect of AGEs scientifically.

 

Batilol is a substance used in cosmetics to reduce inflammation. This publication shows that this is an anti-inflammatory substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)