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EC number: 244-848-1 | CAS number: 22224-92-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- 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
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- 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
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Endpoint summary
Administrative data
Description of key information
Endpoints for skin sensitisation are covered by available animal studies.
The test substance is non-sensitising to skin.
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:
- 1995-07-04 to 1995-07-28
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- dated 29 December 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- adopted 17 July 1992
- Deviations:
- yes
- Remarks:
- see "Principles of method if other than guideline"
- Principles of method if other than guideline:
- Only in 18 animals a topical challenge was administered. OECD guidelines states: ‘when fewer than 20 test guinea pigs have been used in a maximisation test and it is not possible to conclude that the test substance is a sensitiser, testing in additional animals to give a total of at least 20 test and 10 control animals is strongly recommended.’ Since the test substance was very toxic, no further testing is required. The study is considered acceptable. The test substance is considered not sensitising to the skin of guinea pigs.
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- This study was conducted due to non-REACH regulatory requirements. With the existing data from this study not only being acceptable but of good quality (Klimisch Score 1), this study precludes the need for an additional LLNA study. In addition, a supplementary LLNA study would violate the ECHA objectives with regards to animal welfare.
- Species:
- guinea pig
- Strain:
- other: SPF-bred guinea pigs of the strain Hsd Win:DH (previously termed BonDHPW)
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann GmbH Laboratory Animal Breeders in 33176 Borchen
- Microbiological status of animals, when known: SPF
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 331-335 g
- Housing: IV Makrolon® cages with low-dust wood shavings, in groups of five
- Diet (ad libitum): Altromin®3020 - Maintenance Diet for Guinea Pigs supplied by Altromin GmbH in Lage
- Water (ad libitum): tap water
- Acclimation period: at least 7 days
- Indication of any skin lesions: no
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-1.5
- Humidity (%): 40-70
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal
- Vehicle:
- physiological saline
- Remarks:
- containing 2 % v/v Cremophor EL®
- Concentration / amount:
- 2.5 %
- Day(s)/duration:
- Day 1/ -
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Remarks:
- containing 2 % v/v Cremophor EL®
- Concentration / amount:
- 25 %
- Day(s)/duration:
- Day 7/ 48 h
- Adequacy of induction:
- non-irritant substance, but skin pre-treated with 10% SDS
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Remarks:
- containing 2 % v/v Cremophor EL®
- Concentration / amount:
- 12%
- Day(s)/duration:
- Day 21/ 24 h
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Remarks:
- containing 2 % v/v Cremophor EL®
- Concentration / amount:
- 25 %
- Day(s)/duration:
- Day 21/ 24 h
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 18 animals in test substance group (9 animals/ challenge concentration)
10 animals in control group (5 animals/ challenge concentration) - Details on study design:
- RANGE FINDING TESTS:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: intradermal: 2, topical and intradermal
- Exposure period: topical 48 h
- Test groups:
intradermal:
1. Injection site: cranial/bilateral: complete Freund's adjuvant (DIFCO LAB.) diluted 1:1 with physiological NaCI solution (sterile).
2. Injection site: medial/bilateral: 1 % SRA 3886 formulated in sterile physiological saline solution containing 2% v/v Cremophor EL®
3. Injection site: caudal/bilateral: 1% SRA 3886 formulated at equal parts in sterile physiological NaCI solution containing 2% v/v Cremophor EL® and complete Freund's adjuvant.
topical:
0.5 ml SRA 3886 25% in physiological saline solution containing 2% v/v Cremophor EL®.
- Control group:
intradermal:
The animals of the control groups were treated in the same manner as the animals of the test substance group; however, the formulations for injection site pairs 2 and 3 did not contain any test substance but a corresponding amount of sterile physiological NaCI solution containing 2% v/v Cremophor EL®.
topical:
0.5 ml sterile physiological saline solution containing 2% v/v Cremophor EL®.
- Site: dorsal region and the flanks
- Frequency of applications: 3
- Concentrations: intradermal: 2.5 %, topical: 25 %
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day of challenge: Day 21
- Exposure period: 24 h
- Test groups: 2
- Control group: 2
- Site: dorsal region and the flanks
- Concentrations: 12 and 25 %
- Evaluation (hr after challenge): 48 and 72 - Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 0
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- positive control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 0
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 12 %
- No. with + reactions:
- 0
- Total no. in group:
- 18
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 12 %
- No. with + reactions:
- 0
- Total no. in group:
- 18
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 25 %
- No. with + reactions:
- 0
- Total no. in group:
- 18
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 25 %
- No. with + reactions:
- 0
- Total no. in group:
- 18
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 12 %
- No. with + reactions:
- 0
- Total no. in group:
- 18
- Clinical observations:
- none at surviving animals
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 12 %
- No. with + reactions:
- 0
- Total no. in group:
- 18
- Clinical observations:
- none at surviving animals
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 25 %
- No. with + reactions:
- 4
- Total no. in group:
- 18
- Clinical observations:
- none at surviving animals
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 25 %
- No. with + reactions:
- 1
- Total no. in group:
- 18
- Clinical observations:
- none at surviving animals
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of this study, the test substance is considered not sensitising to the skin of guinea pigs.
- Executive summary:
The study was performed in accordance with OECD 406. There were no deviations from the current regulatory guideline considered to compromise the scientific validity of the study. In a skin sensitisation study, according to Magnusson and Kligman (GPMT), the potential of the test item was evaluated to provoke sensitization reactions in guinea pigs. The dose levels were based on the results of range-finding studies. On day 0, three pairs of intradermal injections of 0.1 mL volume were given in the left and the right side of the spinal column:
(1) a 1:1 mixture (v/v) Freund's complete adjuvant with NaCI,(2) the test item (1% suspension of the test item in physiological saline containing 2% v/v Cremophor EL®), (3) 1% of the test item in a 1:1 mixture (v/v) of Freund's complete adjuvant with NaCI solution containing 2% v/v Cremophor EL®.
Seven days after the intradermal induction, the test substance was applied to the test area at a concentration of 25% in physiological saline containing 2% v/v Cremophor EL®, and held in place for 48 hours. Three weeks after the intradermal induction, two hypoallergic patches loaded with 12% and 25% of the test substance were placed on the left flank of the animals and held in contact for 24 hours. The skin reactions were assessed 48 and 72 hours after the initiation of the challenge exposure, according to Magnusson and Kligman grading scale. The animals were observed for clinical signs at least once daily throughout the entire study period.
Two animals of the test group died after intradermal induction. The macroscopic examination revealed paleness of the liver, lungs and kidneys and the stomach was filled with liquid.
In the surviving animals, after 48 h slight skin redness (grade 1) was observed at the 25 % challenge concentration in 4/18 test animals, after 72 h a slight skin redness was observed only in 1 animal. No skin reactions were found at the 12 % challenge concentration in test group and control group animals after 48 and 72 hours.
Based on the obtained results, it can be concluded that the test item has no potential to induce skin sensitization.
Reference
Table 1: Results summary
Animal no. | Callenge: 25 % | Callenge: 12 % | ||
| 48 h | 72 h | 48 h | 72 h |
21 | 0 | 0 | 0 | 0 |
22 | 0 | 0 | 0 | 0 |
23 | 0 | 0 | 0 | 0 |
24 | 0 | 0 | 0 | 0 |
25 | + | + | + | + |
26 | 1 | 0 | 0 | 0 |
27 | 0 | 0 | 0 | 0 |
28 | 1 | 0 | 0 | 0 |
29 | 0 | 0 | 0 | 0 |
30 | 1 | 1 | 0 | 0 |
31 | 0 | 0 | 0 | 0 |
32 | 0 | 0 | 0 | 0 |
33 | + | + | + | + |
34 | 0 | 0 | 0 | 0 |
35 | 0 | 0 | 0 | 0 |
36 | 1 | 0 | 0 | 0 |
37 | 0 | 0 | 0 | 0 |
38 | 0 | 0 | 0 | 0 |
39 | 0 | 0 | 0 | 0 |
40 | 0 | 0 | 0 | 0 |
+ animal died after the first induction (intradermal)
MORTALITY
Two animals of the test group died after intradermal induction. The macroscopic examination revealed paleness of the liver, lungs and kidneys and the stomach was filled with liquid.
SKIN REACTIONS
After 48 h slight skin redness (grade 1) was observed at the 25 % challenge concentration in 4/18 test animals, After 72 h a slight skin redness was observed only in 1 animal. No skin reactions were found at the 12 % challenge concentration in test group and control group animals after 48 and 72 hours.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
The information provided below was taken from the original plant protection dossier on the active substance submitted in 2017 for inclusion of the test substance to Annex I of Directive 91/414/EEC and has been previously evaluated in the Draft Assessment Report (DAR) according to the Commission Regulation (EU) No 1107/2009 (2003) (revisioned in the Renewal Assesment Report (December 2018)) and subject to peer review by EFSA and Member States (2006). The summaries as published in the RAC opinion (2011) are given below.
Skin sensitisation in vivo
Stropp (1995): A guinea pig maximization test was performed in accordance with OECD 406. Twenty males were included in the test group, 10 in the control group. An intradermal induction was used with 1 % test item (based on range-finding studies) after one week followed by the topical induction with 25 % test item, which was performed for 48 h. Three weeks after the intradermal induction, a topical challenge was conducted with 12 and 25 % test item for 24 h. Two animals of the test group died after intradermal induction. The macroscopic examination revealed paleness of the liver, lungs and kidneys and the stomach was filled with liquid. Although only in 18 animals a topical challenge was administered, further testing is not required, due to the high toxicity of the test item. It is concluded that the test substance is not a skin sensitiser.
Watanabe (1983): Another GPMT study, which can only be accepted as supportive because the number of animals was too low (10/dose/group), also did not show sensitising properties of the test substance.
A summary of the results of skin sensitization studies is presented in Table 1.
Table 1: Summary of skin sensitization studies
Test /
ReferenceKey data
CLP
Skin sensitisation in vivo /
Stropp (1995)
not sensitising
Criteria not met Skin sensitisation in vivo / Watanabe (1983)
not sensitising
Criteria not met
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.
Based on available data on skin sensitisation, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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