Registration Dossier
Registration Dossier
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EC number: 285-203-4 | CAS number: 85049-34-9
Endpoint summary
Administrative data
Description of key information
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:
- key study
- Study period:
- 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Comparable to guideline study with acceptable restrictions. Lack of test material details.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- lack of test material details
- GLP compliance:
- not specified
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- A non-LLNA study was available.
- Species:
- guinea pig
- Strain:
- other: Pirbright
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Lippische Versuchstierzucht Hagemann GmbH&Co. KG, Extertal, Germany
- Weight at study initiation: 269 g
- Housing: Groups of 2 animals in Macrolon Plastic cages III (measuring 14 x 25 x 42 cm) with Saniff bedding.
- Diet: pelleted, Alleindiät für Meerschweinchen (Plange Kraftfutterwerk Soest GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- Preliminary study: 25, 50, 75 and 100%
Main study:
Induction: 100% (test substance mixed with a few drops of water)
Challenge: 100% - Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- Preliminary study: 25, 50, 75 and 100%
Main study:
Induction: 100% (test substance mixed with a few drops of water)
Challenge: 100% - No. of animals per dose:
- 10 (controls), 20 (test group)
- Details on study design:
- RANGE FINDING TESTS:
In a preliminary test with 25, 50, 75 and 100% (w/v) of the test substance in water no irritation was noted after 6 h occlusive exposure. Therefore, the test article was applied as 100% (w/v) in a few drops of dest. water.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in dest. water
- Control group: untreated
- Site: shaved left shoulder
- Frequency of applications: every week
- Duration: Day 0-21
- Concentrations: 100%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 35
- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: shaved right shoulder
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 h
OTHER: 24 h after the challenge all animals were depilated with Pilca Cream (Olivin, Hamburg, Germany). - Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Clinical observations:
- -
- Remarks on result:
- not measured/tested
- Remarks:
- not measured
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test substance caused no skin reactions in the preliminary and in the main study in any animal during the study period.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Comparable to guideline study with acceptable restrictions. Lack of test material details.
- Justification for type of information:
- Please refer section 13 for read across justification.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- lack of test material details
- GLP compliance:
- not specified
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- A non-LLNA study was available.
- Species:
- guinea pig
- Strain:
- other: Pirbright
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Lippische Versuchstierzucht Hagemann GmbH&Co. KG, Extertal, Germany
- Weight at study initiation: 269 g
- Housing: Groups of 2 animals in Macrolon Plastic cages III (measuring 14 x 25 x 42 cm) with Saniff bedding.
- Diet: pelleted, Alleindiät für Meerschweinchen (Plange Kraftfutterwerk Soest GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- Preliminary study: 25, 50, 75 and 100%
Main study:
Induction: 100% (test substance mixed with a few drops of water)
Challenge: 100% - Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- Preliminary study: 25, 50, 75 and 100%
Main study:
Induction: 100% (test substance mixed with a few drops of water)
Challenge: 100% - No. of animals per dose:
- 10 (controls), 20 (test group)
- Details on study design:
- RANGE FINDING TESTS:
In a preliminary test with 25, 50, 75 and 100% (w/v) of the test substance in water no irritation was noted after 6 h occlusive exposure. Therefore, the test article was applied as 100% (w/v) in a few drops of dest. water.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in dest. water
- Control group: untreated
- Site: shaved left shoulder
- Frequency of applications: every week
- Duration: Day 0-21
- Concentrations: 100%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 35
- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: shaved right shoulder
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 h
OTHER: 24 h after the challenge all animals were depilated with Pilca Cream (Olivin, Hamburg, Germany). - Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Clinical observations:
- -
- Remarks on result:
- not measured/tested
- Remarks:
- not measured
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- -
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test substance caused no skin reactions in the preliminary and in the main study in any animal during the study period.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 Mar - 20 Jul 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Basic data given (comparable to guideline study). Lack of individual test results and test material details. No data on reliablility check (positive control)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- lack of individual test results and test material details. No data on reliability check (positive control)
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- A non-LLNA study was available.
- Species:
- guinea pig
- Strain:
- other: Pirbright white
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Fa. Winkelmann, Borchen, Germany
- Weight at study initiation: 352.6 g (control group, range finding study) and 349.4 g (treatment group, range finding study); 298.5 g (control group, main study) and 298.4 g (treatment group, main study)
- Housing: animals were housed in groups of 2-3 in Makrolon IV cages
- Diet: Altromin-Haltungsdiät 3032 DK (Fa. Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal and epicutaneous
- Vehicle:
- other: Paraffin perliquid DAB 8
- Concentration / amount:
- Induction: 0.1% (intradermal), 15% (epicutaneous)
Challenge: 2.5 and 5% - Route:
- epicutaneous, occlusive
- Vehicle:
- other: Paraffin perliquid DAB 8
- Concentration / amount:
- Induction: 0.1% (intradermal), 15% (epicutaneous)
Challenge: 2.5 and 5% - No. of animals per dose:
- 2 x 3 (range finding study)
20 (main study) - Details on study design:
- RANGE FINDING TESTS:
Test group A:
To evaluate the concentration for intracutaneous induction 3 guinea pigs were tested with 0.1, 0.5, 1.0 and 2.0% (intracutaneous) of the test substance. The 0.1% concentration of the intracutaneous application caused a sufficient irritation on the skin. Therefore, a 0.1% concentration was chosen for intracutaneous induction exposure.
Test group B:
To evaluate the epicutaneous induction and the challenge concentration, 3 guinea pigs were tested with 5, 10 and 15% (epicutaneous) with the test substance. Due to the only slight skin reactions at 15%, this concentration was chosen for epicutaneous induction and 2.5 and 5% as challenge concentration.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: the test substance in Paraffin perliquid DAB 8
Injection 3: the test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in Paraffin perliquid DAB 8
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: Paraffin perliquid DAB 8
Injection 3: Paraffin perliquid DAB 8 in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in Paraffin perliquid DAB 8
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 0.1%, epicutaneous 15%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: parallel application onto the flank
- Concentrations: 2.5 and 5%
- Evaluation (hr after challenge): 24 and 48 h - Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0.1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0.1%
- No. with + reactions:
- 1
- Total no. in group:
- 20
- Clinical observations:
- slight redness of the skin
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 100 %
- Clinical observations:
- not tested
- Remarks on result:
- not measured/tested
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 100 %
- Clinical observations:
- no tested
- Remarks on result:
- not measured/tested
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- positive control
- Dose level:
- 100 %
- Clinical observations:
- not tested
- Remarks on result:
- not measured/tested
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test substance is determined to be no skin sensitising.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 07 Mar - 20 Jul 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Basic data given (comparable to guideline study). Lack of individual test results and test material details. No data on reliablility check (positive control)
- Justification for type of information:
- Please refer section 13 for read across justification.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- lack of individual test results and test material details. No data on reliability check (positive control)
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- A non-LLNA study was available.
- Species:
- guinea pig
- Strain:
- other: Pirbright white
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Fa. Winkelmann, Borchen, Germany
- Weight at study initiation: 352.6 g (control group, range finding study) and 349.4 g (treatment group, range finding study); 298.5 g (control group, main study) and 298.4 g (treatment group, main study)
- Housing: animals were housed in groups of 2-3 in Makrolon IV cages
- Diet: Altromin-Haltungsdiät 3032 DK (Fa. Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal and epicutaneous
- Vehicle:
- other: Paraffin perliquid DAB 8
- Concentration / amount:
- Induction: 0.1% (intradermal), 15% (epicutaneous)
Challenge: 2.5 and 5% - Route:
- epicutaneous, occlusive
- Vehicle:
- other: Paraffin perliquid DAB 8
- Concentration / amount:
- Induction: 0.1% (intradermal), 15% (epicutaneous)
Challenge: 2.5 and 5% - No. of animals per dose:
- 2 x 3 (range finding study)
20 (main study) - Details on study design:
- RANGE FINDING TESTS:
Test group A:
To evaluate the concentration for intracutaneous induction 3 guinea pigs were tested with 0.1, 0.5, 1.0 and 2.0% (intracutaneous) of the test substance. The 0.1% concentration of the intracutaneous application caused a sufficient irritation on the skin. Therefore, a 0.1% concentration was chosen for intracutaneous induction exposure.
Test group B:
To evaluate the epicutaneous induction and the challenge concentration, 3 guinea pigs were tested with 5, 10 and 15% (epicutaneous) with the test substance. Due to the only slight skin reactions at 15%, this concentration was chosen for epicutaneous induction and 2.5 and 5% as challenge concentration.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: the test substance in Paraffin perliquid DAB 8
Injection 3: the test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in Paraffin perliquid DAB 8
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: Paraffin perliquid DAB 8
Injection 3: Paraffin perliquid DAB 8 in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in Paraffin perliquid DAB 8
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 0.1%, epicutaneous 15%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: parallel application onto the flank
- Concentrations: 2.5 and 5%
- Evaluation (hr after challenge): 24 and 48 h - Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0.1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0.1%
- No. with + reactions:
- 1
- Total no. in group:
- 20
- Clinical observations:
- slight redness of the skin
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 100 %
- Clinical observations:
- not tested
- Remarks on result:
- not measured/tested
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 100 %
- Clinical observations:
- no tested
- Remarks on result:
- not measured/tested
- Reading:
- rechallenge
- Hours after challenge:
- 72
- Group:
- positive control
- Dose level:
- 100 %
- Clinical observations:
- not tested
- Remarks on result:
- not measured/tested
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test substance is determined to be no skin sensitising.
- Endpoint:
- skin sensitisation: in vitro
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Referenceopen allclose all
The test substance caused no skin reactions in the preliminary and in the main study in any animal during the study period.
The test substance caused no skin reactions in the preliminary and in the main study in any animal during the study period.
No mortality was observed in any control or treatment animal.
The individual body weights of the control and test animals showed the expected values.
After intracutaneous induction all animals showed the characteristic reactions after application of FCA (Freund´s complete adjuvant). The test substance without FCA caused moderate skin reactions which were of a lower grade than the reactions caused by FCA alone or by the solution of FCA with the test substance.
After patch removal after the second induction (epicutaneous induction) bloody skin alterations were observed. Later on, this skin reactions changed to necrotic and escharic skin reactions.
24 and 48 h after patch removal (challenge induction) no skin reaction was observed in the treatment animals. In 1 control animal (animal No. 16; 48 h reading) a slight reaction was apparent. According to the author, the results were therefore not presented in table form.
No mortality was observed in any control or treatment animal.
The individual body weights of the control and test animals showed the expected values.
After intracutaneous induction all animals showed the characteristic reactions after application of FCA (Freund´s complete adjuvant). The test substance without FCA caused moderate skin reactions which were of a lower grade than the reactions caused by FCA alone or by the solution of FCA with the test substance.
After patch removal after the second induction (epicutaneous induction) bloody skin alterations were observed. Later on, this skin reactions changed to necrotic and escharic skin reactions.
24 and 48 h after patch removal (challenge induction) no skin reaction was observed in the treatment animals. In 1 control animal (animal No. 16; 48 h reading) a slight reaction was apparent. According to the author, the results were therefore not presented in table form.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
There are no data for sensitisation available for the target substance. In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VII, 8.3.
According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”.
The target substance Fatty acids, C16-18 and C18-unsatd., esters with propylene glycol represents a UVCB substance predominantly comprised of diesters of an aliphatic diol (1,2-propyleneglycol (PG)) chemically linked to mainly oleic acid (C18:1) but as well to palmitic acid (C16), palmitoleic acid (C16:1), stearic acid (C18) and/or linoleic acid (C18:2). Glycol esters are in general known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid component and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972).
Based on the common metabolic fate of glycol esters, the read-across approach is based on the presence of common functional groups, common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals, common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.
As no data are available on skin sensitization of the target substance, read-across to reliable data on the analogue substances Ethylene distearate (CAS 627-83-8) and Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3) was conducted.
CAS 627-83-8
The skin sensitising properties of Ethylene distearate were evaluated according to a Buehler test protocol similar to OECD guideline 406 in Hartley guinea pigs (Müller, 1982. The solid test material was mixed with a few drops of water and was applied at a concentration of 100% for epidermal induction (exposure once/week between Day 0 – 21 with an occlusive patch placed on the left shoulder for 6 h at each occasion) and challenge (exposure on Day 35 with an occlusive patch placed on the right shoulder for 6 h). The negative control group was treated with the vehicle only. No positive control data was included in the study report for reliability check. At challenge, the neat test substance induced no skin effects in the test and negative control group. No further skin reactions after induction and challenge were observed.
Based on the available data, Ethylene distearate is not sensitising.
CAS 29059-24-3
Skin sensitization of Myristic acid, monoester with propane-1,2-diol was tested in a GLP-compliant Guinea pig maximization test according to EU Method B.6 (Kästner, 1989). 20 female Pirbright white guinea pigs were induced with a single intradermal injection of the test substance at 0.1% in Paraffin perliquid DAB 8 and with an epicutaneous occlusive application of the test substance at 15% on the shoulder region 7 days later. A negative control group of 20 animals was treated with Paraffin perliquid DAB 8 only. Epicutaneous challenge exposure was conducted 20 days after the first induction for 24 h under occlusive conditions at test substance concentrations of 2.5% and 5%, respectively. All test and control animals showed no skin reactions after 24 and 48 h with one exception only. In one control animal, slight redness of the skin after 48 h was apparent. No positive control data was included in the study report for reliability check.
In summary, Myristic acid, monoester with propane-1,2-diol did not exhibit skin sensitizing properties in the conducted study.
Conclusion on skin sensitising properties
The available data investigating the sensitisation properties of read-across analogue substances consistently showed negative results. Thus, there is no evidence to consider the target substance as skin sensitising.
References
Agency for Toxic Substances and Disease Registry (ATSDR) (1997). Toxicological Profile for Propylene Glycol. US Department of Health and Human Services. Atlanta, US.
Agency for Toxic Substances and Disease Registry (ATSDR) (2010). Toxicological Profile for Ethylene Glycol. US Department of Health and Human Services. Atlanta, US.
Lehninger, A.L. (1970). Biochemistry. Worth Publishers, Inc.Long, C.L. et al. (1958). Studies on absorption and metabolism of propylene glycol distearate. Arch Biochem Biophys, 77(2):428-439.
Mattson, F.H. and Volpenhein, R.A. (1972). Hydrolysis of fully esterified alcohols containing from one to eight hydroxyl groups by the lipolytic enzymes of the rat pancreatic juice. Journal of Lipid Research 13: 325-328
Miller, O.N., Bazzano, G. (1965).Propanediol metabolism and its relation to lactic acid -metabolism. Annals of the New York Academy of Sciences 119:957-973.
Ritchie, A.D. (1927). Lactic acid in fish and crustacean muscle. Journal of Experimental Biology 4: 327-332.
Short description of key information: skin sensitisation (Bühler, GPMT): not sensitising
Justification for selection of skin sensitisation endpoint: Hazard assessment is conducted by means of a read-across based on a read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Additional information:
Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.
Justification for classification or non-classification
Based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 , and are therefore conclusive but not sufficient for classification.
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.
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