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EC number: 309-629-8 | CAS number: 100545-48-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
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- Density
- Particle size distribution (Granulometry)
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- Endpoint summary
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- Environmental data
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
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- Sediment toxicity
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- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
The potential of the substance to induce
delayed contact hypersensitivity was investigated using the Maximization
method of Magnusson and Kligman (OECD 406, GLP) . It was advisable to
conduct a Guinea Pig Maximisation Test rather than a Local Lymph Nodes
Assay because the substance contained an impurity which was known to
give a false positive result in the Local Lymph Nodes Assay. The result
of the Guinea Pig Maximisation Test indicates that the substance was a
skin sensitizer.
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:
- From 02 August 2012 to 17 September 2012
- 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 (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Justification for conducting a Guinea Pig Maximisation Test rather than a Local Lymph Node Assay:
The test item is a complex substance which contains 12 -hydroxystearic acid (12 -HSA) (EC n° 203 -366 -1, CAS n°106 -14 -9) as an impurity. 12-HSA is an unbranched fatty acid of C18 chain length with an hydroxyl group in C12.
In the context of its REACH registration, 12-HSA was tested for sensitization in a Local Lymph Node Assay (LLNA) and the study produced a positive response (Sanders A., 2012).
For the following reasons, the response seen in the LLNA study with 12-HSA was considered as a false positive:
- From a structural point of view, 12-HSA does not contain electrophilic groups that could potentially trigger skin sensitization reactions. (Q)SAR analysis suggests that 12-HSA is not a sensitizer,
- 12-HSA has a history of safe use in consumer products with substantial skin contact (e.g. cosmetics, laundry and cleaning products), with no evidence of skin sensitization issues. Furthermore, experience from worker exposure to 12-HSA at both production and handling sites suggests that the substance does not cause sensitizing effects,
- During the validation of the LLNA study, the observation was made that this assay often overestimates the sensitization potential for some substances, e.g. surfactants, fatty acids, fatty alcohols and siloxanes (Ball et al., 2011). Testing conducted with a number of fatty acids showed that some cause positive effects in the LLNA test but are then negative in the GMPT study. The LLNA results are therefore considered to be false positives. This is the case for 12-HSA which was recently tested in a GPMT study and gave negative results.
For the above mentioned reasons, it was advisable to conduct a Guinea Pig Maximisation Test rather than a Local Lymph Nodes Assay for assessing the skin sensitization potential of the test substance. - Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: breeder: Charles River Laboratories France, L’Arbresle, France
- Age at study initiation: Approximately 1 to 2 months old on the day of treatment
- Mean body weight at study initiation: The males had a mean body weight of 360 g (range: 284 g to 393 g) and the females had a mean body weight of 352 g (range: 276 g to 382 g)
- Fasting period before study: No
- Housing: Polycarbonate cages with stainless steel lid
- Diet: 106 pelleted diet (free access)
- Water: Tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: At least 5 days before the beginning of the study.
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h
IN-LIFE DATES: 07 August 2012 to 17 September 2012. - Route:
- intradermal and epicutaneous
- Vehicle:
- other: Corn oil for intradermal induction injections; ethanol/water for topical induction dose and acetone for topical challenge dose
- Concentration / amount:
- Concentration for intradermal injection: 5%
Concentration for topical application: 25% - Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Corn oil for intradermal induction injections; ethanol/water for topical induction dose and acetone for topical challenge dose
- Concentration / amount:
- Concentration for topical application: 10%
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- Main test: 10 control animals and 20 treated animals (15 males and 15 females).
- Details on study design:
- RANGE FINDING TESTS: conducted to define the concentrations to be tested in the main study
-Intradermal exposure:
Hair over the scapulae was removed using electric clippers before treatment.
Intradermal administration of 0.1 ml of the test material (TM) was given at increasing concentrations. The dosage form preparation did not pass into the dermis at the concentrations of 10% and 25%. Therefore concentrations of 5% in corn oil was tested in 2 animals.
Evaluation of the potential cutaneous reactions: 24, 48 hours and 6 days after injection
- Epicutaneous exposure:
Hair over the scapulae was removed using electric clippers before treatment.
Each selected concentration was applied to a filter paper patch measuring 8cm2 for 48 hours under occlusive dressing . 2 concentrations (10% and 25% w/v in ethanol/drinking water treated by reverse osmosis (80/20) were tested in 2 animals.
Evaluation of the potential cutaneous reactions: 24 and 48 hours after patch removal.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 epicutaneous
- Exposure period: epicutaneous: 48 hours
-> TEST GROUPS:
Intradermal exposure
Three injections of 0.1 mL were injected into each side of the animal as follows:
. Freund's complete adjuvant (FCA) diluted to 50% with sterile water
. TM at 5 % w/v in vehicle
. TM at 5% w/v in a 50/50 (v/v) mixture of FCA and sterile water
Epicutaneous exposure
Application of 8 cm2 patch saturated with the TM at 25% to the scapular region and held in place for 48 hours using an occlusive dressing.
-> CONTROL GROUP:
Intradermal exposure
Three injections of 0.1 mL were injected into each side of the animal as follows:
. Freund's complete adjuvant (FCA) diluted to 50% with sterile water
. vehicle
. A mixture 50/50 (v/v) FCA diluted to 50% with sterile water, and vehicle
Epicutaneous exposure
Application of 8 cm2 patch saturated with the vehicle to the scapular region and held in place for 48 hours using an occlusive dressing.
- Site:
Intradermal exposure
6 injections in the clipped area (3x 4cm) in the scapular region
Epicutaneous exposure
3x 4cm area over the scapulae
- Frequency of applications:
One intradermal injection and one epicutaneous application on Day 8 on the same site.
- Duration:
Epicutaneous exposure: 48 hours
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 hours
-> TEST GROUPS:
Challenge: TM at 10% in the vehicle on the right flank and vehicule on the left flank (occlusive epicutaneous application)
-> CONTROL GROUPS:
Same treatment as test group
- Site: posterior flanks
- Evaluation (hr after challenge): 24 , 48 hours after removal of the dressing according to the method of Draize. - Challenge controls:
- Control animals received vehicle only.
- Positive control substance(s):
- yes
- Remarks:
- Mercaptobenzothiazole
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5% intradermal injection
- No. with + reactions:
- 14
- Total no. in group:
- 20
- Clinical observations:
- discrete or moderate erythema, associated with dryness of the skin
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5% intradermal injection
- No. with + reactions:
- 15
- Total no. in group:
- 20
- Clinical observations:
- discrete or moderate erythema, associated with dryness of the skin and edema
- Remarks on result:
- positive indication of skin sensitisation
- 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:
- no indication of skin sensitisation
- 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:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 1% intradermal injection
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- The test substance induced delayed contact hypersensitivity in 15 out of 20 (75%) guinea pigs with an intradermal induction dose of 5% .
Since more than 30% of the animals responded at an intradermal induction dose of more than 1%, the substance is considered as a moderate sensitizer and is therefore classified Skin Sensitizer category 1 and sub- category 1B according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures. - Executive summary:
The potential of the test substance to induce delayed contact hypersensitivity was assessed in guinea pigs according to OECD guideline 406 and in compliance with Good Laboratory Practice.
The induction phase was realized both by the intradermal route on day 1 (Test material 5% in corn oil) and by the cutaneous route on day 8 (Test material 25% in ethanol/drinking water treated by reverse osmosis 80/20) in 2 groups of guinea pigs: 10 in the control group and 20 in the treated group. The challenge phase was realized on day 22 by cutaneous application of the test material at 10% in acetone. The cutaneous reactions were scored 24 and 48 hours after the challenge phase.
In the control group, at the 24 and 48 hour readings, no cutaneous reactions were observed. In the treated group, a discrete or moderate erythema (grade1 or 2) associated with dryness of the skin, was noted in 13 of the 20 animals at the 24 hour reading
At the 48 hour reading, a discrete or moderate erythema (grade 1 or 2) was observed in 14 of the 20 animals, associated with dryness of the skin for 6 of them and oedema for 4 of them. In addition, at the 24 and 48 hour readings, an intense erythema (grade 3), associated with oedema and dryness of the skin was observed in 1 of the 20 animals.
The persistent cutaneous reactions observed in 15 of the 20 animals of the test item-treated group were attributed to delayed contact hypersensitivity.
It was therefore concluded that the test substance was a skin sensitizer.
Reference
The preliminary study indicated that the test material injected at a 5% concentration was reasonably well tolerated. Concentrations of 25% and 10% were selected for the topical induction and the challenge phase respectively.
Table 7.4.1/2 Individual skin reactions after challenge
Group |
Sex |
Animal number |
Skin reactions (Hour after removal of dressings) |
|||
24 hours |
48 hours |
|||||
LF |
RF |
LF |
RF |
|||
Control group |
Male |
Y40443 |
0 |
0 |
0 |
0 |
Y40444 |
0 |
0 |
0 |
0 |
||
Y40445 |
0 |
0 |
0 |
0 |
||
Y40446 |
0 |
0 |
0 |
0 |
||
Y40447 |
0 |
0 |
0 |
0 |
||
Female |
Y40473 |
0 |
0 |
0 |
0 |
|
Y40474 |
0 |
0 |
0 |
0 |
||
Y40475 |
0 |
0 |
0 |
0 |
||
Y40476 |
0 |
0 |
0 |
0 |
||
Y40477 |
0 |
0 |
0 |
0 |
||
Treated group |
Male |
Y40448 |
0 |
1 |
0 |
1 |
Y40449 |
1 |
2/S |
0 |
2/S/Oe |
||
Y40450 |
0 |
2 |
0 |
1 |
||
Y40451 |
0 |
3/S/Oe |
0 |
3/S/Oe |
||
Y40452 |
0 |
0 |
0 |
0 |
||
Y40453 |
0 |
2 |
0 |
2 |
||
Y40454 |
0 |
1 |
0 |
2/S |
||
Y40455 |
0 |
2 |
0 |
2/S |
||
Y40456 |
0 |
1 |
0 |
2 |
||
Y40457 |
0 |
2 |
0 |
2/S |
||
Female |
Y40478 |
0 |
2/S |
0 |
2/Oe |
|
Y40479 |
0 |
2 |
0 |
2/S |
||
Y40480 |
0 |
0 |
0 |
1 |
||
Y40481 |
0 |
0 |
0 |
0 |
||
Y40482 |
0 |
1 |
0 |
2/Oe/S |
||
Y40483 |
0 |
1 |
0 |
2 |
||
Y40484 |
0 |
0 |
0 |
0 |
||
Y40485 |
0 |
0 |
0 |
0 |
||
Y40486 |
0 |
0 |
0 |
0 |
||
Y40487 |
0 |
1 |
0 |
2/Oe |
LF = Left flank (vehicle)
RF = Right flank (test item at the concentration of 10%)
S= Dryness of the skin
Oe=Oedema
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
The potential of the test substance to induce delayed contact hypersensitivity was assessed in guinea pigs according to OECD guideline 406 and in compliance with Good Laboratory Practice.
The induction phase was realized both by the intradermal route on day 1 (Test material 5% in corn oil) and by the cutaneous route on day 8 (Test material 25% in ethanol/drinking water treated by reverse osmosis 80/20) in 2 groups of guinea pigs: 10 for the control group and 20 for the treated group. The challenge phase was realized on day 22 by cutaneous application of the test material at 10% in acetone. The cutaneous reactions were scored 24 and 48 after the challenge phase.
In the control group, at the 24 and 48 hour readings, no cutaneous reactions were observed. In the treated group, a discrete or moderate erythema (grade 1 or 2) associated with dryness of the skin, was noted in 13 out of 20 animals at the 24 hour reading.
At the 48 hour reading, a discrete or moderate erythema (grade 1 or 2) was observed in 14 out of 20 animals, associated with dryness of the skin for 6 of them and oedema for 4 of them. In addition, at the 24 and 48 hour readings, an intense erythema (grade 3), associated with oedema and dryness of the skin was observed in 1 out of 20 animals.
The persistent cutaneous reactions observed in 15 out of 20 animals of the test item-treated group were attributed to delayed contact hypersensitivity.
It was therefore concluded that the test substance was a skin sensitizer.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The test substance induced delayed contact hypersensitivity in 15 out of 20 (75%) guinea pigs with an intradermal induction dose of 5% .
Since more than 30% of the animals responded to an intradermal induction dose of more than 1%, the substance is considered as a moderate sensitizer and is therefore classified as a Skin Sensitizer category 1 and sub- category 1B according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.
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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