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Registration Dossier
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EC number: 203-118-2 | CAS number: 103-50-4
Endpoint summary
Administrative data
Description of key information
The results of two GPMTs (guinea pigs maximisation test) and a LLNA
(local lymph node assay) were available.
The results from 3 studies examining the skin sensitisation potential of
dibenzyl ether are available. The endpoint conclusion was drawn on a
weight-of-evidence consideration of the 3 studies.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1996
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The study was conducted in 1996. At this time point no valid guideline for a LLNA was available (the original Test Guideline (TG) for the determination of skin sensitization in the mouse, the Local Lymph Node Assay (LLNA; TG 429) was adopted in 2002).
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles river, 76410 St Aubin les Elbeuf, France)
- Weight at study initiation: 324-375 g
- Housing: in individual propylene cage in accordance with 86/609/EEC
- Diet (e.g. ad libitum): complete pelleted diet UAR 106
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days
No further information - Route:
- intradermal and epicutaneous
- Vehicle:
- olive oil
- Remarks:
- and mineral oil
- Concentration / amount:
- 5 % in olive oil or in a mixture of 1:1 (v/v) of FCA and distilled water
- Route:
- epicutaneous, occlusive
- Vehicle:
- olive oil
- Remarks:
- and mineral oil
- Concentration / amount:
- 5 % in olive oil or in a mixture of 1:1 (v/v) of FCA and distilled water
- No. of animals per dose:
- 20 guinea-pigs dosed and 10 as negative controls.
- Details on study design:
- RANGE FINDING TESTS:
Determination of the MNIC on three guinea-pigs.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Six days and five days in the second induction phase
- Test groups:
Group 1:
Injection 1: mixture of 1:1 (v/v) of FCA and distilled water
Injection 2: olive oil
Injection 3: 50 % vehicle (W/v) in a mixture 1:1 (v/v) of FCA and distilled water
Group 2:
Injection 1: mixture of 1:1 (v/v) of FCA and distilled water
Injection 2: test material 5 % in olive oil
Injection 3: test material 5 % in mixture of 1:1 (v/v) of FCA and distilled water
- Site: shoulder region
B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: about Two days, one under occlusive conditions and one open air and then cleaned
- Evaluation (hr after challenge): 24 hours and 48 hours (2 nd reading)
- Concentration: 50 and 20 %
No further information - Challenge controls:
- No data reported
- Positive control substance(s):
- yes
- Remarks:
- 2-mercapto benzothiazole
- Positive control results:
- 70 % reactive animals at the 48 hr reading at 5 or 2 % with mineral oil.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- vehicle
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- vehicle
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 20 %
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20 %. No with. + reactions: 3.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 20 %
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20 %. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 50 %
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 %. No with. + reactions: 3.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 50 %
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 %. No with. + reactions: 2.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- vehicle
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- vehicle
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 20 %
- No. with + reactions:
- 5
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20 %. No with. + reactions: 5.0. Total no. in groups: 20.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 20 %
- No. with + reactions:
- 3
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20 %. No with. + reactions: 3.0. Total no. in groups: 20.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50 %
- No. with + reactions:
- 5
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 5.0. Total no. in groups: 20.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50 %
- No. with + reactions:
- 5
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 5.0. Total no. in groups: 20.0.
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- positive control
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- 70 % reactive animals at the 48 hr reading at 5 or 2 % with mineral oil.
- Interpretation of results:
- GHS criteria not met
- Executive summary:
The authors tested the sensitizing potential of dibenzyl ether (CAS n° 103-50-4) in guinea-pig maximization test based on the OECD guideline 406. No deviations to the guideline were observed. Twenty female guinea-pigs were tested and 10 females were included in a negative control. Earlier in the year, a positive control had already been conducted. The induction and challenge phase were conducted accordingly with the OECD requirements.
In the test conditions, the authors showed the percentage of animals showing skin reaction in the tested group was approximately similar to the percentage for controls. in view of these results, skin responses observed in the test animals should be considered as due in part to irritation induced by the test substance. Hence, based on the CLP criteria, since less than 30 % of test animals showed a skin reaction at the two readings, dibenzyl ,oxide should not be considered as a sensitizer for the skin.
This study is performed according to OECD guideline 406. GLP standards are respected and no deviations to the guideline were observed. Thus this study is considered reliable without restrictions, a Klimisch 1 study.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Sensitisation test in guinea pigs according to a modified Draize procedure which is not in compliance with actual gudilines
- Principles of method if other than guideline:
- A modified Draize procedure was used to test natural and synthetic perfume ingredients for their potential to induce allergic contact dermatitis.
- GLP compliance:
- not specified
- Type of study:
- Draize test
- Justification for non-LLNA method:
- Study was published in 1978 (Toxicology 9, 261-271 (1978).
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male/female
- Route:
- intradermal
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.1 ml
- Route:
- intradermal and epicutaneous
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.1 ml
- No. of animals per dose:
- Ten guinea pigs (either 4 males and 6 females or visa versa).
- Reading:
- 1st reading
- Group:
- test chemical
- Remarks on result:
- other: no individual scores reported
- Reading:
- 2nd reading
- Group:
- test chemical
- Remarks on result:
- other: no individual scores reported
- Reading:
- 1st reading
- Group:
- negative control
- Remarks on result:
- other: no individual scores reported
- Reading:
- 1st reading
- Group:
- positive control
- Remarks on result:
- other: no individual scores reported
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Executive summary:
A modified Draize procedure was used to test natural and synthetic perfume ingredinents for their potential to induce allergic contact dermatitis. Dibenzyl ether was sensitizing after 2 sensitisation treatments. Individual scores were not reported.
The method used in this test is no standard procedure. Therefore the results have limited validity.
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- not specified
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/ca/Ola/Hsd
- Sex:
- female
- Vehicle:
- other: 1:3 ethanol:diethyl phthalate
- Concentration:
- 25 µl of 1.0, 2.5, 5.0, 10 or 25% (w/v).
- No. of animals per dose:
- 24 female mice.
- Parameter:
- SI
- Remarks on result:
- other: The EC3 value was calculated to be 6.3% (1575 µg/cm²)
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Executive summary:
In a LLNA a dose of ca. 25 µl of 25 µl of 1.0, 2.5, 5.0, 10 or 25% (w/v) dibenzyl ether in 1:3 ethanol:diethyl phthalate was applied topically to the ear lobes of mice. Three days after the third topical application the mice were injected a buffered solution of 20µCi [3]H-methyl thymidine into the tail veins. Five hours later, the animals were killed, the lymph nodes excised and the desintegrations per minute (dpm) and the stimulation index (SI) determined.
Under the conditions of the study, dibenzyl ether is a weak sensitiser. The EC3 value was calculated to be 6.3% (1575 µg/cm²).
Referenceopen allclose all
In the test conditions, the authors showed the percentage of animals showing skin reaction in the tested group was approximately similar to the percentage for controls. In view of these results, skin responses observed in the test animals should be considered as due in part to irritation induced by the test substance. Hence, based on the CLP criteria, since less than 30 % of test animals showed a skin reaction at the two readings, dibenzyl ether should not be considered as a sensitizer for the skin.
Dibenzyl ether was sensitizing after 2 sensitisation treatments.
Under the conditions of the study, dibenzyl ether is a weak sensitiser.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
In a GLP conform Guinea pig maximisation test (GPMT) according to OECD 406 (study with no deviations) a negative result was found. Under the conditions of the test, the authors showed the percentage of animals showing skin reaction in the tested group was approximately similar to the percentage for controls. In view of these results, skin responses observed in the test animals should be considered as due in part to irritation induced by the test substance. Hence, based on the CLP criteria, since less than 30 % of test animals showed a skin reaction at the two readings, dibenzyl ether should not be considered as a sensitizer for the skin.
In a second GPMT a modified Draize procedure was used to test natural and synthetic perfume ingredients for their potential to induce allergic contact dermatitis. Dibenzyl ether was sensitizing after 2 sensitisation treatments. Individual scores were not reported.
The method used in this test is no standard procedure. Therefore the results have limited validity.
In a LLNA a dose of ca. 25 µl of 25 µl of 1.0, 2.5, 5.0, 10 or 25% (w/v) dibenzyl ether in 1:3 ethanol:diethyl phthalate was applied topically to the ear lobes of mice. Three days after the third topical application the mice were injected a buffered solution of 20µCi [3]H-methyl thymidine into the tail veins. Five hours later, the animals were killed, the lymph nodes excised and the desintegrations per minute (dpm) and the stimulation index (SI) determined.
Under the conditions of the study, dibenzyl ether is a weak sensitiser. The EC3 value was calculated to be 6.3% (1575 µg/cm²).
A positive and a negative GPMT is available. The LLNA was positive. Overall, by a weight of evidence consideration dibenzyl ether is regarded as a weak sensitiser.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Additional information:
No data.
Justification for classification or non-classification
A positive (Sharp, 1978) and a negative (Baque, 1996) GPMT is available. The data from the positive GPMT are not sufficient for a subclassification. In the LLNA (Betts, 2007) the EC3 value was calculated to be 6.3% (1575 µg/cm²).
According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Skin Sens. 1B; H 317: may cause an allergic skin reaction) is justified.
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