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EC number: 251-136-4 | CAS number: 32647-67-9
- 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
The skin sensitisation potential of the substance (EC 251-136-4) has been assessed by reading across the results of skin sensitisation studies conducted on two structurally similar analogue substances, which are detailed below.
Source Substance; Gel All DX (EC-413 -110 -2):
A study was performed to assess the contact sensitisation potential of the test material (EC 413-110-2) in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" and Method B6 of Commission Directive 92/69/EEC.
Ten test and five control animals were used for the main study.
Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:
- lntradermal lnduction: 0.5 % w/v in arachis oil BP
- Topical lnduction: 25 % w/w in arachis oil BP
- Topical Challenge: 10 % and 5 % w/w in arachis oil BP
The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
Source Substance; Gel All MD (EC 402-950-5):
A modification of the Buehler method (OECD 406) was used to assess the skin sensitisation potential of technical Gel-All-MD (EC 402-950-5)
Following a preliminary study designed to determine the maximum non-irritant and minimum irritant concentrations, a 40% w/w concentration of the test material in 0.5% aqueous carboxymethyl cellulose was applied topically to the 10 animals within the test group, for a period of 6 hours. This procedure was repeated at weekly intervals for a period of three weeks. A further 10 animals forming the control group, remained untreated during this stage of the study.
After 14 days all animals were challenged using 40% and 20% w/w concentartions of the test material. Assessments of dermal reactions were made 24, 48 and 72 hours after the challenge application.
No evidence of any dermal reaction to treatment was seen after challenging with either 40 or 20% w/w concentrations of the test material.
It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Please see Section 13 for "Read-across justification to support the REACH registration of Bis-O-(benzylidene)-D-glucitol (EC 251-136-4) at 10-100 tpa" for full details.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance:
IUPAC name: 1,3:2,4-bis-O-((3,4-dimethylphenyl)methylene) D-Glucitol
EC number: 413-110-2
CAS number: 135861-56-2
Target Substance: Bis-O-(benzylidene)-D-glucitol
IUPAC name: 1,3:2,4-bis-O-dibenzylidene-D-glucitol
EC number: 251-136-4
CAS number: 32647-67-9
3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data (and toxicokinetic behaviour assessment) it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.
4. DATA MATRIX
Please see Section 13 for "Read-across justification to support the REACH registration of Bis-O-(benzylidene)-D-glucitol (EC 251-136-4) at 10-100 tpa" for full details. - Reason / purpose for cross-reference:
- read-across source
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test material produced a 0 % (0110) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
- Executive summary:
A study was performed to assess the contact sensitisation potential of the test material (structural analogue source substance EC 413-110-2) in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" and Method B6 of Commission Directive 92/69/EEC.
Ten test and five control animals were used for the main study.
Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:
- lntradermal lnduction: 0.5 % w/v in arachis oil BP
- Topical lnduction: 25 % w/w in arachis oil BP
- Topical Challenge: 10 % and 5 % w/w in arachis oil BP
The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
It is proposed that this result can be used in the assessment of the target substance.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29 September 1997- 31 October 1997
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Available study report from 1998.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffodshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 311- 374 g
- Housing: animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 22 °C
- Humidity (%): 42- 62 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal and epicutaneous
- Vehicle:
- arachis oil
- Concentration / amount:
- Intradermal: 0.5%, Topical: 25%
- Route:
- epicutaneous, occlusive
- Vehicle:
- arachis oil
- Concentration / amount:
- 10% and 5%
- No. of animals per dose:
- Sighting tests:
Intradermal induction: 4/ sex/ dose
Topical Induction: 2/ sex were treated with 4 preparations
Topical challange: 2/ sex were treated with 4 preparations
Main study: 10/ sex/ dose - Details on study design:
- RANGE FINDING TESTS:
The concentrations of test material to be used at each stage of the main study were determined by 'sighting tests' in which groups of guinea pigs were treated with various concentrations of test material. The procedures were as follows:
-Selection of Concentration for lntradermal lnduction:
Four concentrations of test material were investigated (0.1 %, 0.5 %, 1 % and 5 % w/v in arachis oil BP). A total of 4 guinea pigs wereused, each guinea pig receiving four 0.1 mL injections of only 1 concentration of test material. The degree of erythema at the injection sites was assessed approximately 24, 48 and 72 h and 7 d after injection according to the Draize scale. The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.
-Selection of Concentration for Topical lnduction:
Two guinea pigs (intradermally injected with Freund's Complete Adjuvant 17 days earlier) were treated with 4 preparations of the test material (50 %, 25 %, 10 % and 5 % w/w in arachis oil BP). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 h. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 h after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.
-Selection of Concentration for Topical Challenge:
Four preparations of the test material (25 %, 10 %, 5 % and 2 % w/w in arachis oil BP) were applied to the clipped flanks of 2 guinea pigs under occlusive dressings for an exposure period of 24 h. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to Day 14. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 h after dressing removal. The highest non-irritant concentration of the test material and one lower concentration was selected for the topical challenge stage of the main study.
MAIN STUDY
- Test group: 1 group of 10 animals
- Control group: 1 group of 5 animals
A. INDUCTION EXPOSURE
- No. of exposures: 2; intradermal and topical
- Exposure period: 48 h (topical induction)
- Site: 40 mm x 20 mm on the shoulder region
Induction of test animals
- Shortly before treatment on Day 0 the hair was removed from an area approximately 40 mm x 60 mm on the shoulder region of each animal with veterinary clippers. A row of 3 injections (0.1 mL each) was made on each side of the mid-line. The injections were:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) a 0.5 % w/v formulation of the test material in arachis oil BP
c) a 0.5 % w/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.
Approximately 24 and 48 hours after intradermal injection the degree of erythema at the test material injection sites (ie. Injection site b) was evaluated.
-One week later (Day 7), the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of the test material formulation. A filter paper patch loaded with the test material formulation (25 % w/w in arachis oil BP) as a thick, even layer was applied to the prepared skin and held in place with a strip of surgical adhesive tape covered with an overlapping length of aluminium foil. The patch and foil were further secured with a strip of elastic adhesive wound in a double layer around the torso of each animal. This occlusive dressing was kept in place for 48 h.
- The degree of erythema and oedema was quantified 1 and 24 h following removal of the patches. Any other reactions were also recorded.
Induction of the control animals
-lntradermal injections were administered using an identical procedure to that used for the test animals, except that the injections were:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) arachis oil BP
C) a 50 % w/v formulation of arachis oil BP in Freund's Complete Adjuvant/distilled water 1:1
Approximately 24 and 48 hours after intradermal injection the degree of erythema at the vehicle injection sites was evaluated.
- The topical applications followed the same procedure as for the test animals except that the vehicle alone was applied to the filter paper. Skin reactions were quantified as for the test animals.
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 h
- Site: 20 mm x 20 mm
- Concentrations: 5 % and 10 % w/w in arachis oil BP
- Evaluation (hr after challenge): 24 and 48 h after challange dressing removal, the degree of erythema and oedema was quantified.
- Shortly before treatment on Day 21, an area of approximately 50 mm x 70 mm on both flanks of each animal, was clipped free of hair with veterinary clippers. A square filter paper patch loaded with a thick, even layer of test material at the maximum non-irritant concentration (10 % w/w in arachis oil BP) was applied to the shorn right flank of each animal and was held in place with a strip of surgical adhesive tape. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 5 % w/w in arachis oil BP was similarly applied to a skin site on the left shorn flank. The patches were occluded with an overlapping length of aluminium foil and secured with a strip of elastic adhesive bandage wound in a double layer around the torso of each animal.
After 24 h, the dressing was carefully cut using blunt-tipped scissors, removed and discarded. The challenge sites were swabbed with cotton wool soaked in diethyl ether to remove residual material. The position of the treatment sites was identified by using a black indelible marker-pen. Prior to the 24-h observation the flanks were clipped using veterinary clippers to remove regrown hair. - Positive control substance(s):
- yes
- Remarks:
- The guinea pig strain used has been shown to produce satisfactory senisitisation responses using known positive sensitisers
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10 %
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5 %
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10 %
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5 %
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None noted.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 10 %
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 5 %
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 10 %
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 5 %
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None noted.
- Interpretation of results:
- not sensitising
- Conclusions:
- The test material produced a 0 % (0110) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
- Executive summary:
A study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" and Method B6 of Commission Directive 92/69/EEC.
Ten test and five control animals were used for the main study.
Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:
- lntradermal lnduction: 0.5 % w/v in arachis oil BP
- Topical lnduction: 25 % w/w in arachis oil BP
- Topical Challenge: 10 % and 5 % w/w in arachis oil BP
The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- The study was conducted between March 1988 and April 1988
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Principles of method if other than guideline:
- The test method is a modification of one of the accepted methods of test for skin sensitisation described in guideline No. 406 for the testing of chemicals, Organistaion for the Economic Cooperation and Development. The procedures that were used were those described by Buehler E.V., Arch, Dermatol. 91, 171-175, 1965.
- GLP compliance:
- yes
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- Available study report from 1988.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent, Staffordshire
- Age at study initiation: 4 to 11 weeks
- Weight at study initiation: Animals weighed between 357 and 433g
- Housing: Animals were housed in groups of 2 in grid-bottomed polypropylene cages and indentified within the cage by ear markings.
- Diet: A commercially available pelleted diet was provided with additional vitamin C - ad libitum
- Water: free access to tap water - ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 28 deg C
- Humidity (%): between 31 and 64%
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): 12 hours light follwed by 12 hours of darkness - Route:
- epicutaneous, occlusive
- Vehicle:
- CMC (carboxymethyl cellulose)
- Concentration / amount:
- 40%
- Route:
- epicutaneous, occlusive
- Vehicle:
- CMC (carboxymethyl cellulose)
- Concentration / amount:
- 40% and 20%
- No. of animals per dose:
- 10
- Details on study design:
- RANGE FINDING TESTS:
On the day before dosing the flanks of four guinea pigs were clipped free of fur using a clipper. On the day of dosing four concentrations of the test material were prepared. These concentrations were 0.5, 5, 10 , 20 and 40% in aqueous carboxymethyl cellulose (CMC). 0.5g of each concentration was applied to a 20mm square of absorbent lint BPC which was in turn applied to a different skin site on the flank of each animal. These patches were then occluded for six hours using "Blenderm" occlusive tape and secured using an adhesive bandage. 24 and 48 hours after treatment commenced the treated sites were examined under a standard light source. Any response to the treatment was assessed.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: ten female Dunkin Hartley rats
- Control group: yes
- Site: left shoulder
- Frequency of applications: Days 1, 8 and 15
- Concentrations:0.5 g of 40% w/w of test material in 0.5% w/v aqeous CMC
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 29
- Exposure period: 6 hours
- Test groups: ten female Dunkin Hartley rats
- Control group: yes
- Site: left and right flank
- Concentrations: 20% and 40% concentrations
- Evaluation (hr after challenge): 24, 48 and 72 hours after application of dressing - Challenge controls:
- 40% and 20% concentrations were also used in the challenge phase for control animals.
- Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 20%
- 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:
- test chemical
- Dose level:
- 40%
- 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:
- test chemical
- Dose level:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 20%
- 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:
- 40%
- 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:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- not sensitising
- Conclusions:
- It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
- Executive summary:
A modification of the Buehler method (OECD 406) was used to assess the skin sensitisation potential of technical Gel-All-MD.
Following a preliminary study designed to determine the maximum non-irritant and minimum irritant concentrations, a 40% w/w concentration of the test material in 0.5% aqueous carboxymethyl cellulose was applied topically to the 10 animals within the test group, for a period of 6 hours. This procedure was repeated at weekly intervals for a period of three weeks. A further 10 animals forming the control group, remained untreated during this stage of the study.
After 14 days all animals were challenged using 40% and 20% w/w concentartions of the test material. Assessments of dermal reactions were made 24, 48 and 72 hours after the challenge application.
No evidence of any dermal reaction to treatment was seen after challenging with either 40 or 20% w/w concentrations of the test material.
It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Please see Section 13 for "Read-across justification to support the REACH registration of Bis-O-(benzylidene)-D-glucitol (EC 251-136-4) at 10-100 tpa" for full details.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance:
IUPAC name: 1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol
EC number: 402-950-5
CAS number: 87826-41-3
Target Substance: Bis-O-(benzylidene)-D-glucitol
IUPAC name: 1,3:2,4-bis-O-dibenzylidene-D-glucitol
EC number: 251-136-4
CAS number: 32647-67-9
3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data (and toxicokinetic behaviour assessment) it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.
4. DATA MATRIX
Please see Section 13 for "Read-across justification to support the REACH registration of Bis-O-(benzylidene)-D-glucitol (EC 251-136-4) at 10-100 tpa" for full details. - Reason / purpose for cross-reference:
- read-across source
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 20%
- 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:
- test chemical
- Dose level:
- 40%
- 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:
- test chemical
- Dose level:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 20%
- 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:
- 40%
- 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:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 40%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 20%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
- Executive summary:
A modification of the Buehler method (OECD 406) was used to assess the skin sensitisation potential of technical Gel-All-MD (structural analogue substance EC 402-950-5)
Following a preliminary study designed to determine the maximum non-irritant and minimum irritant concentrations, a 40% w/w concentration of the test material in 0.5% aqueous carboxymethyl cellulose was applied topically to the 10 animals within the test group, for a period of 6 hours. This procedure was repeated at weekly intervals for a period of three weeks. A further 10 animals forming the control group, remained untreated during this stage of the study.
After 14 days all animals were challenged using 40% and 20% w/w concentartions of the test material. Assessments of dermal reactions were made 24, 48 and 72 hours after the challenge application.
No evidence of any dermal reaction to treatment was seen after challenging with either 40 or 20% w/w concentrations of the test material.
It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
It is proposed that this result can be used in the assessment of the target substance.
Referenceopen allclose all
-Skin Reactions Observed After Topical Challenge:
No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-h observations.
lntradermal and Topical Sighting Tests
Intradermal sighting test- summary of results. Vehicle: arachis oil BP
Animal identification |
Time of observation |
Concentration of test material (% w/v) |
Grade of erythema at injection sites |
Evidence of systemic toxicity |
A |
24 h |
1 |
3 |
None |
48 h |
3-4N* |
None |
||
72 h |
3-4N* |
None |
||
7 d |
0 |
None |
||
B |
24 h |
5 |
3-4N |
None |
48 h |
4NE |
None |
||
72 h |
4E |
None |
||
7 d |
4E |
None |
||
C |
24 h |
0.1 |
1-2 |
None |
48 h |
2 |
None |
||
72 h |
2 |
None |
||
7 d |
1 |
None |
||
D |
24 h |
0.5 |
1-2 |
None |
48 h |
2-3 |
None |
||
72 h |
2 |
None |
||
7 d |
1 |
None |
E= eschar; N= green necrosis; N*= possible necrosis
Topical sighting test for induction application (48-h exposure)- individual skin reactions. Vehicle: arachis oil BP
Animal identification |
Concentration of test material (% w/w) |
Skin reaction (hours after removal of patches) |
||||||||
1 |
24 |
48 |
||||||||
Er |
Oe |
Other |
Er |
Oe |
Other |
Er |
Oe |
Other |
||
E |
50* |
2 |
2 |
- |
2 |
0 |
- |
1 |
0 |
- |
25 |
2 |
2 |
- |
2 |
0 |
- |
1 |
0 |
D |
|
10 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
5 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
F |
50* |
3 |
2 |
- |
2 |
1 |
- |
1 |
0 |
- |
25 |
2 |
2 |
- |
2 |
1 |
- |
1 |
0 |
D |
|
10 |
1 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
5 |
1 |
1 |
- |
0 |
0 |
- |
0 |
0 |
- |
Er= erythema; Oe= oedema; -= no other reactions noted; D= desquamation; *= maximum attainable concentration suitable for topical application
Topical sighting test for challenge application (24-h exposure)- individual skin reactions. Vehicle: arachis oil BP
Animal identification |
Concentration of test material (% w/w) |
Skin reaction (hours after removal of patches) |
||||||||
1 |
24 |
48 |
||||||||
Er |
Oe |
Other |
Er |
Oe |
Other |
Er |
Oe |
Other |
||
G |
25* |
2 |
2 |
- |
1 |
0 |
- |
0 |
0 |
- |
10 |
2 |
2 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
5 |
2 |
1 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
2 |
2 |
1 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
H |
25* |
2 |
2 |
- |
1 |
1 |
- |
0 |
0 |
- |
10 |
2 |
1 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
5 |
1 |
1 |
- |
0 |
0 |
- |
0 |
0 |
- |
|
2 |
1 |
1 |
- |
0 |
0 |
- |
0 |
0 |
- |
Er= erythema; Oe= oedema; -= no other reactions noted; *= maximum attainable concentration suitable for topical application
Based on these results, the following concentrations were selected for the main study:
Intradermal induction: 0.5 % w/v in arachis oil BP
Topical induction: 25 % w/w in arachis oil BP
Topical challenge: 10 % and 5 % w/w in arachis oil BP
Main study
-Skin Reactions Observed After lntradermal lnduction:
Well-defined erythema was noted at the intradermal induction sites of all test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the intradermal induction sites of all control group animals at the 24-h observation and in 4 control group animals at the 48-h observation.
-Skin Reactions Observed After Topical lnduction:
Very slight to well-defined erythema was noted at the induction sites of all test group animals at the 1-h observation with very slight erythema at the induction sites of 9 test group animals at the 24-h observation. Bleeding from the intradermal induction sites was noted in 5 test group animals at the 1-h observation. Residual test material was noted in all test group animals. Bleeding from the intradermal induction sites was noted in 1 control group animal at the 1-h observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24-h observations.
-Skin Reactions Observed After Topical Challenge:
No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-h observations.
-Bodyweight:
Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.
No evidence of dermal reaction to treatment was seen in any of the test or control animals challenged with 40% and 20% w/w concentrations of the test material in 0.5% w/v aqueous carboxymethyl cellulose.
No evidence of dermal reaction to treatment was seen in any of the test or control animals challenged with 40% and 20% w/w concentrations of the test material in 0.5% w/v aqueous carboxymethyl cellulose.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
It is proposed that the results from the read-across source substances can be used in the assessment of the target substance.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The substance (EC 251-136-4), based on the results of skin sensitisation studies conducted on two structurally similar substances, is not classified for skin sensitisation.
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.