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EC number: 211-492-3 | CAS number: 652-67-5
- 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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Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- The study was performed between 22 December 2009 and 12 January 2010.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 1,4:3,6-dianhydro-D-glucitol
- EC Number:
- 211-492-3
- EC Name:
- 1,4:3,6-dianhydro-D-glucitol
- Cas Number:
- 652-67-5
- Molecular formula:
- C6H10O4
- IUPAC Name:
- 1,4:3,6-dianhydro-D-glucitol
- Details on test material:
- Sponsor's identification: ISOSORBIDE
Supplier : ROQUETTE FRERES
Batch number : E1143
CAS number : 652-67-5
Purity : 99.8%
Moisture : 0.3%
Description : white solid
Molecular formula: C6H10O4
Molecular weight: 146.16 g/mol
Solubility : highly soluble in water
pH : 5.0 – 7.0
Stability : stable with respect to storage conditions
Appearance : solid flakes
Date received : 24 November 2009
Expiry date : 24 March 2010
Storage conditions: room temperature in the dark
Intended use : industrial chemical
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/Ca (CBA/CaOlaHsd)
- Sex:
- female
- Details on test animals and environmental conditions:
- Female CBA/Ca (CBA/CaOlaHsd) strain mice were supplied by Harlan Laboratories UK Limited, Bicester, Oxon, UK.
On receipt the animals were randomly allocated to cages. The animals were nulliparous and non pregnant.
After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink
marking on the tail and a number written on a cage card.
At the start of the study the animals were in the weight range of 15 to 23 g, and were eight to twelve weeks old.
The animals were individually housed in suspended solid floor polypropylene cages furnished with softwood woodflakes.
Free access to mains tap water and food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed
throughout the study.
The temperature and relative humidity were controlled to remain within target ranges of 19 to 25°C and 30 to 70%, respectively. Any occasional
deviations from these targets were considered not to have affected the purpose or integrity of the study.
The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06.00 to 18.00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have
affected the purpose or integrity of the study.
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Remarks:
- Please see below for Vehicle Determination Record
- Concentration:
- Each group was exposed to concentrations of 50%, 25% or 10% w/w in dimethyl formamide.
- No. of animals per dose:
- Groups of four mice were treated
- Details on study design:
- RANGE FINDING TESTS:
Using available information regarding the systemic toxicity/irritancy potential of the test material, a preliminary screening test was performed using
one mouse. The mouse was treated by daily application of 25 µl of the test material at a concentration of 50% w/w in dimethyl formamide to the
dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The mouse was observed twice daily on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Any signs of toxicity or excessive local irritation noted during this period were recorded. The bodyweight was recorded on Day 1 (prior to dosing) and on Day 6.
- Lymph node proliferation response:
Clinical observations, bodyweight and mortality data are give in the results section (table 1).
No signs of systemic toxicity were noted.
Based on this information the dose levels selected for the main test were 50%, 25% and 10% w/w in dimethyl formamide.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
Local Lymph Node Assay in the Mouse. The assay has undergone extensive inter-laboratory validation and has been shown to reliably detect test
materials that are moderate to strong sensitisers.
- Criteria used to consider a positive response:
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node(dpm/node) and as the ratio of 3HTdR incorporation in lymph node cells of test nodes relative to that recorded for the control nodes (stimulation Index).
The test material will be regarded as a sensitiser if at least one concentration of the test material results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test material failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non-sensitier".
TREATMENT PREPARATION AND ADMINISTRATION:
For the purpose of the study, the test material was freshly prepared in dimethyl formamide. This vehicle was chosen as it produced the most suitable
formulation at the required concentration. The concentrations used are given above.
Determination, by analysis, of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not
specified in the Study Plan and is not a requirement of the Test Guidelines.
The preliminary screening test suggested that the test material would not produce systemic toxicity or excessive local irritation at the highest
suitable concentration. The mice were treated by daily application of 25 µl of the appropriate concentration of the test material to the dorsal surface
of each ear for three consecutive days (Days 1, 2 and 3). The test material formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
3H-Methyl Thymidine Administration:
Five days following the first topical application of the test material (Day 6) all mice were injected via the tail vein with 250 µl of phosphate buffered
saline (PBS) containing 3H-methyl thymidine (3HTdR: 80 µCi/ml, specific activity 2.0 Ci/mmol, GE Healthcare UK Ltd) giving a total of 20 µCi to each mouse. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- None provided.
Results and discussion
- Positive control results:
- One group of five animals was treated with 50 µl (25 µl per ear) of alpha-Hexylcinnamaldehyde, Tech, 85% as a solution in dimethyl formamide at a
concentration of 15% v/v. A further group of five animals was treated with dimethyl formamide alone.
The Stimulation Index expressed as the mean radioactive incorporation for the treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:
Concentration % v/v in dimethyl formamide Stimulation Index (SI) Result
15 5.16 Positive
Alpha-Hexylcinnamaldehyde, Tech 85% was considered to be a sensitiser under the conditions of the test.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: A stimulation index of less than 3 was recorded for the test material at concentrations of 50%, 25% and 10% w/w in dimethyl formamide. The stimulation index (SI) results are given in Table 2 in section any other information on results.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: The radioactive disintegrations per minute (dpm) per lymph node and the stimulation index (SI) are given in Table 2 in section any other information on results.
Any other information on results incl. tables
Concentration (%w/w) in |
Animal Number |
Bodyweight (g) |
Day |
|||||||||
1 |
2 |
3 |
4 |
5 |
6 |
|||||||
Day 1 |
Day 6 |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
|||||
50 |
S-1 |
18 |
19 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 = No signs of systemic toxicity
Table 2 Disintegrations per Minute, Disintegrations per Minute/Node and Stimulation Index
Concentration |
dpm |
dpm/Nodea |
Stimulation Indexb |
Result |
Vehicle |
9416.03 |
1177.00 |
na |
na |
10 |
6655.76 |
831.97 |
0.71 |
Negative |
25 |
5216.33 |
652.04 |
0.55 |
Negative |
50 |
5179.54 |
647.44 |
0.55 |
Negative |
dpm= Disintegrations per minute
a= Disintegrations per minute/node obtained by dividing the disintegrations per minute value by 8 (total number of lymph nodes)
b= Stimulation Index of 3.0 or greater indicates a positive result
na = Not applicable
Table 3 Individual Clinical Observations and Mortality Data
Concentration |
Animal Number |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
|||
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
|||||
Vehicle |
1-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
10 |
2-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
25 |
3-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
50 |
4-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
4-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0= No signs of systemic toxicity
Table 4 Individual Bodyweights and Bodyweight Changes
Concentration |
Animal Number |
Bodyweight (g) |
Bodyweight Change (g) |
|
Day 1 |
Day 6 |
|||
Vehicle |
1-1 |
18 |
19 |
1 |
1-2 |
18 |
19 |
1 |
|
1-3 |
18 |
19 |
1 |
|
1-4 |
19 |
21 |
2 |
|
10 |
2-1 |
18 |
20 |
2 |
2-2 |
19 |
21 |
2 |
|
2-3 |
19 |
20 |
1 |
|
2-4 |
20 |
20 |
0 |
|
25 |
3-1 |
21 |
20 |
-1 |
3-2 |
19 |
19 |
0 |
|
3-3 |
20 |
20 |
0 |
|
3-4 |
21 |
21 |
0 |
|
50 |
4-1 |
19 |
19 |
0 |
4-2 |
18 |
18 |
0 |
|
4-3 |
18 |
16 |
-2 |
|
4-4 |
19 |
19 |
0 |
Current Positive Control Study for the Local Lymph Node Assay
Introduction.
A study was performed to assess the sensitivity of the strain of mouse used at these laboratories to a known sensitiser. The methodology for the LLNA is detailed in the OECD Guideline for the Testing of Chemicals, No. 429, and Method B.42 of CommissionRegulation (EC) No. 440/2008. The study described in this document is based on these test methods but has been refined in order to reduce the number of animals required. The reduced LLNA (rLLNA) has been endorsed by the non‑Commission members of the European Centre for the Validation of Alternative Methods (ECVAM) Scientific Advisory Committee (ESAC) at its 26thmeeting held on 26 – 27 April 2007 at ECVAM,Ispra, Italy.
Test Material: α-Hexylcinnamaldehyde, tech., 85%
Project number: 0039/1116
Study dates: 11 November 2009 to 17 November 2009
Methods.
A group of five animals was treated with 50 µl (25 µl per ear) ofα‑Hexylcinnamaldehyde, tech., 85%as a solution in dimethyl formamideata concentration of 15% v/v. A further control group of five animals was treated with dimethyl formamide alone.
Results.
The Stimulation Index expressed as the mean radioactive incorporation for the treatment group divided by the mean radioactive incorporation of the vehicle control group is as follows:
Concentration (% v/v) in |
Stimulation Index |
Result |
15 |
5.16 |
Positive |
Conclusion.
α-Hexylcinnamaldehyde, tech., 85%was considered to be a sensitiser under the conditions of the test.
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- The test material was considered to be a non-sensitiser under the conditions of the test.
- Executive summary:
A study was performed to assess the skin sensitisation potential of the test material in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. The method was designed to meet the requirements of the following:
§ OECD Guideline for the Testing of Chemicals No. 429 "Skin Sensitisation: Local Lymph Node Assay" (adopted)
§ Method B42 Skin Sensitisation (Local Lymph Node Assay) of Commission Directive 2004/73/EC
Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of50% w/w, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of four animals, were treated with 50 µl (25 µl per ear) of the test material as a solution in dimethyl formamide at concentrations of 50%, 25% or 10% w/w. A further group of four animals was treated with dimethyl formamide alone.
The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:
Concentration (% w/w) in dimethyl formamide
Stimulation Index
Result
5
1.86
Negative
10
1.68
Negative
25
1.69
Negative
The test material was considered to be a non sensitiser under the conditions of the test.
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