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EC number: 907-728-6 | CAS number: -
- 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
Endpoint summary
Administrative data
Description of key information
Skin sensitisation: sensitising (sensitizer 1B), based on read-across from Prismantol, which was tested in OECD TG 406.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- GPMT test
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- The study was performed between 17 September and 12 October 1991.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Justification for type of information:
- The information is used for read across to Rosmarel. The GPMT test with Prismantol was performed before LLNA or in vitro tests became the first test of selection.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- (1981)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The GPMT test was performed before LLNA or in vitro tests became the first test of selection.
- Specific details on test material used for the study:
- The test substance was gently melted in a water bath at 60°C and prepared prior to each application in Alembicol D.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Sex: females, nulliparous and non-pregnant
- Age at Acclimatization Start: ap. 6 to 7 weeks of age
- Weight at Acclimatization Start: 304 to 353 g
- Housing: in groups of ten in suspended metal cages with wire mesh floors.
- Diet: a vitamin C-enriched guinea-pig Diet F.D.1. and drinking water were provided ad libitum. Hay was given weekly to provide dietary supplement. The routine analyses of diet and water was done.
- Water: free access to tap water
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal
- Vehicle:
- other: Alembicol D
- Remarks:
- Supplied by Alembic Products, Saltney, Chester, England
- Concentration / amount:
- 7.5%
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Alembicol D
- Remarks:
- Supplied by Alembic Products, Saltney, Chester, England
- Concentration / amount:
- 60%
- Day(s)/duration:
- 48 h
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Alembicol D
- Remarks:
- Supplied by Alembic Products, Saltney, Chester, England
- Concentration / amount:
- 25 and 50%
- Day(s)/duration:
- 24 h
- No. of animals per dose:
- Test animals: 20
Control animals: 10 - Details on study design:
- RANGE FINDING TESTS
- Intradermal injections:
Intradermal injections were made into the clipped flank of animals at concentrations of 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5 and 10.0% of the test substance in Alembicol D. The reactions were examined after 24 and 72 hours for size, erythema and oedema.
As well-defined erythema (grade 2) was observed with 7.5% in both animals, this concentration was selected as the intradermal induction concentration.
- Epidermal application:
Patches of filter paper (2x4 cm) were saturated with 0.4 ml of the undiluted test substance at the concentration of 60% in Alembicol D. These were applied to the clipped and shaved flanks of each of 2 males and 2 females and were covered by a length of impermeable plastic adhesive tape. This was firmly secured by elastic adhesive bandage wrapped around the trunk and fixed with "Sleek" impervious plastic adhesive tape. The patches were removed 48 hours after application and the treatment sites were examined immediately and 24 hours and 48 hours after removal of the patches.
At 60% in three animals only very slight erythema (grade 1) was observed immediately after patch removal and in three animals after 24 and 48 hours, in one animal a well-defined erythema (grade 2) was observed after 24 and 48 hours, and in one animal a necrotic patch was observed. Therefore, this concentration was used for the topical induction concentration.
As at 50% no erythema was observed at any time of observation, this concentration was used for the highest challenge exposure.
MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal injections (0.1 ml)
- Concentration: 7.5%
- Site: the dorsal scapular region
Three pairs of intradermal injections:
1) Freund's complete adjuvant (FCA) 50:50 with water for irrigation
2) Test substance at 7.5% in Alembicol D
3) Test substance at 7.5% in Alembicol D in a 50:50 mixture of FCA with Alembicol D
Control group:
1) Freund's complete adjuvant (FCA) 50:50 with water for irrigation
2) Alembicol D
3) 50:50 mixture of FCA with water for irrigation
- Readings: daily
- Results: Erythema and edema was observed in both groups
2) Topical applications one week after the injections:
- Concentration: 60%
- Amount: saturated patch (control animals: water for irrigation only)
- Area: 8 cm2
- Exposure period: 48 hours (occlusive)
- Readings: immediately after patch removal and 24 and 48 hours after patch removal
B. CHALLENGE EXPOSURE (control and test group)
- Day of challenge: 2 weeks after the epidermal induction application
- Concentrations: 25 and 50%
- Exposure period: 24 hours (occlusive)
- Sites: left flank, anterior and posterior sites
- Amount: saturated patch
- Readings: at 24, 48 and 72 hours after patch removal - Positive control substance(s):
- yes
- Remarks:
- Formalin
- Positive control results:
- The results of the latest sensitivity check of August-September 1991 showed that the system was responsive (10 of 10 animals reacted positive).
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 20
- Total no. in group:
- 20
- Clinical observations:
- Localized dermal reactions, dryness and sloughing of the epidermis
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 19
- Total no. in group:
- 20
- Clinical observations:
- Localized dermal reactions, dryness and sloughing of the epidermis
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 5% and 1% formalin
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- other: Skin sensitizer Category 1B
- Remarks:
- According to EU CLP (EC/1272/2008 and its amendments).
- Conclusions:
- In a guinea pig maximisation test performed similar to OECD 406 (1981) and according to GLP principles, the substance is considered a 1B skin sensitiser.
- Executive summary:
The skin sensitisation potential of Prismantol was tested in a guinea pig maximisation test performed similar to OECD 406 (1981) and according to GLP principles. A concentration of 7.5% was used for the intradermal induction, 60% for the epidermal induction and 25 and 50% for the topical challenge. The substance produced evidence of skin sensitization in all tested twenty animals and therefore was considered a skin sensitiser. Because ≥ 30% (100%) of animals responded at a dose of > 1% (7.5%), Prismantol is 1B sensitizer.
- Endpoint:
- skin sensitisation: in vitro
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- GPMT test
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Read across information
- Justification for type of information:
- The full read-across document can be found in the Endpoint Summary in text and in the attached file.
- Reason / purpose for cross-reference:
- read-across source
- Justification for non-LLNA method:
- The GPMT test was performed before LLNA or in vitro tests became the first test of selection.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 20
- Total no. in group:
- 20
- Clinical observations:
- Localized dermal reactions, dryness and sloughing of the epidermis
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 19
- Total no. in group:
- 20
- Clinical observations:
- Localized dermal reactions, dryness and sloughing of the epidermis
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 5% and 1% formalin
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- other: Skin sensitizer Category 1B
- Remarks:
- According to EU CLP (EC/1272/2008 and its amendments).
- Conclusions:
- Skin sensitisation: sensitising (sensitizer 1B), based on read-across from Prismantol, which was tested in OECD TG 406.
Referenceopen allclose all
Preliminary study:
- At topical application of 60% no edema was observed at any time point and in three animals a very slight erythema (grade 1) was observed immediately after patch removal and in all four exposed animals after 24 and 48 hours, of which in one animal a well-defined erythema (grade 2) was observed after 24 and 48 hours, and in one animal a necrotic patch was observed. Therefore, this concentration was used for the topical induction concentration. As at 50% no erythema was observed at any time of observation, this concentration was used for the highest challenge exposure.
Main study:
- The body weight gain of the animals was normal, no signs of ill health, no systemic toxicity and no mortality was seen.
- The ten animals exposed to negative control did not show any signs of irritation.
- Intradermal injections: Application area around the injection sites (at 7.5%) was found to show a slight irritation.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
For assessing the skin sensitization of Rosemarel, read across from Prismantol (CAS# 122760-84-3) is used. First the data of Prismantol will be presented and thereafter the read across justification. For Rosemarel also a HRIPT study is available, which cannot be used to assess the skin sensitization potential sufficiently, in accordance with REACH.
Skin sensitization with Prismantol:
The skin sensitisation potential of Prismantol was tested in a guinea pig maximisation test performed similar to OECD 406 (1981) and according to GLP principles. A concentration of 7.5% was used for the intradermal induction, 60% for the epidermal induction and 25 and 50% for the topical challenge. The substance produced evidence of skin sensitization in all tested twenty animals and therefore was considered a skin sensitiser. Because ≥ 30% (100%) of animals responded at a dose of > 1% (7.5%), Prismantol is 1B sensitizer.
Rosemarel and its sensitising potential using read across from Prismantol (CAS 122760-84-3)
Introduction and hypothesis for the analogue approach
Rosemarel is a multi-constituent. The major part is the constituent Beta-pinene (51%) and this constituent has a hexyl ring bridged with one carbon, to which two methyl groups are attached. At the alpha position there is a double bonded methyl group attached to the hexyl ring, which is the functional group. The minor constituent (36%) has the same backbone. The functional group is an epoxide in the place where there is the double bonded methyl group in the other component. For Rosemarel limited skin sensitisation data are available, which are not sufficient to make a decision for this endpoint. Therefore, additional information is used in accordance with Article 13 of REACH where it is said that lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, SARs, grouping and read-across.
Hypothesis: Rosemarel is expected to have the same sensitising properties and potency as Prismantol.
Available experimental information: For the target substance, Rosemarel, only one HRIPT is available, which, according to the REACH guidance, cannot cover the skin sensitisation endpoint. For the source chemical, Prismantol, a well conducted GPMT is available showing a sensitization potential (IFF, 1992; GLP, according to OECD 406, K1). In this study, the intradermal induction was done at 7.5% and the topical induction at 60%, and the topical challenge was done at 50 and 25%. All 20 animals had a positive reaction at 25%. Therefore, Prismantol is a weak sensitizer 1B (≥ 30% of animals responding at a dose > 1%). This study with Prismantol will be used for read-across.
Target and Source chemical(s):
The target is Rosemarel, and the source is Prismantol. The information on the target and source substances, together with their physico-chemical properties, is presented in the data matrix below.
Purity / Impurities:
Rosemarel consists of Beta-pinene (51 %) and its oxidised form- the epoxide (36 %). The impurities are all below < 10%. The purity of the source Prismantol is reported to be 97%.
Analogue justification
According to REACH Annex XI, an analogue approach and structural alert information can be used to replace testing when information from different sources provides sufficient evidence to conclude that this substance has or does not have a particular dangerous property. The result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.
Analogue selection:
First, the information on Beta-pinene was assessed, for which skin sensitisation information is available. Whether this would cover also Rosemarel’s epoxide constituent was questioned at first. Beta-pinene however is not expected to be a skin sensitizer and using Beta-pinene as an analogue would not account for the epoxide component of Rosemarel. Therefore, instead of Beta-pinene, IFF prefers to use Prismantol from its own portfolio because this substance also has an alcohol as a functional group and potentially reflects some similar reactivity as Rosemarel’s epoxide.
Structural analogy:
The main constituent of Rosemarel, Beta-pinene, has a very similar structure as Prismantol. Both substances have the same hexyl backbone being bridged with one or more carbons. They both have a carbon attached to this ring with a double bond. Beta-pinene has no other functional groups while Prismantol has an alcohol attached to the hexyl ring. Rosemarel’s epoxide has this group at the site of the double bond. An epoxide is more reactive compared to an alcohol.
Bioavailability:
Rosemarel (both constituents) has similar molecular weight, log Kow and water solubility as Prismantol, indicating similar dermal bioavailability. The difference in appearance between Rosemarel and Prismantol, liquid versus solid, is unlikely to present a difference in reactivity.
Reactivity:
Rosemarel’s Beta-pinene constituent will be oxidized in the skin and form an epoxide causing similar skin sensitisation potential. Also Prismantol will become oxidized in skin and becomes an epoxide, which makes it very similar to Rosemarel once in skin. Therefore, similar reactivity between Rosemarel and Prismantol is anticipated.
Remaining uncertainties:
There are no remaining uncertainties. Rosemarel’s Beta-pinene constituent has a similar potency as Prismantol. Rosemarel’s epoxide is expected to have a similar potency compared to the oxidised Beta-pinene and therefore Prismantol can be used for read across.
Conclusions per endpoint for C&L and risk assessment
For Rosemarel insufficient skin sensitisation information is available and the analogue Prismantol information on skin sensitisation can be used for read across. Prismantol is sensitizing in a GPMT test (OECD TG 406) in all twenty tested animals. The positive reactions were seen in ≥ 30% of animals (100%) after application of a dose > 1% (7.5%), it is a sensitizer 1B. Based on read across from Prismantol, Rosemarel is expected to be a skin sensitizer 1B.
Data matrix information on Rosemarel and Prismantol important for assessment of skin sensitising properties
Name of substance
Rosemarel
Prismantol
Beta-pinene
Target
Source
Supporting (LLNA is available)
Chemical structure
Empirical
C10H16 and C10H16O
C12H18O
C10H16
Cas No
127-91-3 and 6931-54-0, respectively
122760-84-3
127-91-3
REACH registration
To be registered for 2018
NONS
Registered (2010)
EINECS
-
406-330-5
242-060-2
Mol weight
136.24 and 152.24
178.28
136.24
Phys-chem
EpiSuite predictions (C) and
IFF measured (for both constituents)
EpiSuite predictions (C) and
IFF measured
Appearance
Colourless to slight yellow liquid (IFF, 2016)
White crystal
Melting point (oC)
<-20 (IFF, 2016)
50.74 (C)
42.5 - 49°C (IFF)
Boiling point (oC)
173.85 (C)
172.2 (IFF, 2016)
258.98 (C)
Vapour pressure (Pa at 25oC)
345.9 (IFF, 2016)
0.14 (C)
0.5 (IFF)
Water solubility (mg/l)
7.1 and 338 (C)
45.7 (IFF, 2016)
318.6 (C)
1266 (IFF)
Log Kow
4.35 and 2.95 (C)
3.2-3.4 (IFF, 2016)
3.23 (C)
2.85 (IFF)
Human health
Skin sensitization
Read across from Prismantol
Sensitizer in GPMT
(OECD TG 406);
Negative in LLNA up to 30%
(OECD TG 429)
Positive in LLNA at 29%
(OECD TG 429)
C: calculated value, the physico-chemical data were generated with EPISuite (version 4.1).
Justification for classification or non-classification
Rosemarel is a skin sensitizer based on read across from Prismantol, which was tested in a GPMT test. Based on fact that ≥ 30% (100%) of animals responded at a dose > 1% (7.5%) of Prismantol, Rosemarel has to be classified for skin sensitisation, according to EU CLP (EC1272/2008 and its amendments): Category 1B, H317: May cause an allergic skin reaction.
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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