Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 231-303-8 | CAS number: 7488-56-4
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 17 January 2018 - 27 March 2018.
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The study was conducted in accordance to relevant test guidelines in a GLP accredited laboratory. However, as there was a poor dose response an EC3 value could not be calculated but was instead estimated. The results are considered to be indicative of a “false positive” as they do not follow the known trend for the selenium containing group of substances and is therefore discarded. Please refer to Section 13.2 - Weight of Evidence Approach for the Assessment of Skin Sensitisation Potential of Selenium Disulphide, CAS 7488-56-4, EC 231-303-8 for further information.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- yes
- Remarks:
- see "Any other information on materials and methods incl. tables"
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Selenium disulphide
- EC Number:
- 231-303-8
- EC Name:
- Selenium disulphide
- Cas Number:
- 7488-56-4
- Molecular formula:
- S2Se
- IUPAC Name:
- selenium disulphide
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- No further specific details.
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- Source: Envigo, San Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33049 Italy
Hygienic level: SPF at arrival; standard housing conditions during the study
Justification of strain: On the basis of relevant OECD Guideline, mice of CBA/Ca or CBA/J strain can be used. Females are used because the existing database is predominantly based on females.
Number of animals: 4 animals/groups
Sex: Female, nulliparous, non-pregnant
Age of animals at starting: 8 weeks old (age-matched, within one week)
Body weight range at starting: 18.1-19.6 grams (The weight variation in animals involved in the study did not exceed ± 20 % of the mean weight.)
Acclimatization time:at least 7 days
Note: In the preliminary experiments mice of 9-10 weeks of age (17.4-18.4 g) were used.
Husbandry
Animal health: Only healthy animals were used for the study. Health status was certified by the staff Veterinarian.
Housing / Enrichment: Group caging / mice were provided with glass tunnel-tubes
Cage type: Type II. polypropylene/ polycarbonate
Bedding: Bedding was available to animals during the study
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 15.3 – 28.4 °C
Relative humidity: 23 - 96 %
Ventilation: 15-20 air exchanges/hour
The temperature and relative humidity were recorded twice every day during the acclimatisation and experimental phases.
Food and feeding
Animals received ssniff® SM Rat/Mouse – Breeding and Maintenance, 15 mm, autoclavable “Complete feed for Rats and Mice – Breeding and Maintenance" (Batch number: 382 24962, Expiry date: 30 April 2018, respectively; produced by ssniff Spezialdiäten GmbH (Ferdinand-Gabriel-Weg 16, D-59494 Soest, Germany), and Gel diet Transport (Batch numbers: 60172230020101 and 60180640040101, Expiry dates: 11 August 2018 and 05 March 2019, respectively) produced by Scientific Animal Food & Engineering, Route de Saint Bris, 89290 Augy, France, ad libitum. The food was considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Water supply
Animals received tap water taken from the municipal supply and provided in a 500 ml bottle, ad libitum. Water quality control analysis was performed once every three months and microbiological assessment was performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József Attila u.36, Hungary). Copies of the relevant Certificates of Analysis are retained in the Archive at Citoxlab Hungary Ltd.
Bedding
Bedding of certified wood chips especially designed to keep animals in the best natural environment was provided for animals during the study. Lignocel 3/4-S Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH + Co.KG (Holzmühle 1, 73494 Rosenberg, Germany) was available to animals during the study. Certified Nest building material was also provided for animals (Arbocel produced by J. Rettenmaier & Söhne GmbH + Co.KG).
Identification
A unique number written on the tail with a permanent marker identified each animal. The animal number was assigned on the basis of Citoxlab Hungary Ltd.’s master file. The cages were marked with identity cards with information including study code, cage number, and dose group, sex and individual animal number. The animals were randomised and allocated to the experimental groups. The randomisation was checked by computer software according to the actual body weights, verifying the homogeneity and variability between the groups.
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Preliminary study test concentrations: 25, 10, 5, 2.5 and 1 %
Main study test concentrations: 2.5, 1, 0.5 and 0.25 % - No. of animals per dose:
- 4 animals per dose
- Details on study design:
- ADMINISTRATION OF THE TEST ITEM
Dose Selection and Justification of Dose Selection
The Preliminary Irritation/Toxicity Tests were conducted according to the Study Plan on CBA/CaOlaHsd mice using five doses (2 animals/dose) at test item concentrations of 25, 10, 5, 2.5 and 1 % (w/v) in AOO. The preliminary experiments were conducted in a similar experimental manner to the main study, but were terminated on Day 6 and the radioactive proliferation assay was not performed.
The maximum concentration of test item in an acceptable solvent was established according to OECD guideline 429. Based on the observation of the solubility test, the maximum achievable concentration was 25 % (w/v).
In the Preliminary Irritation / Toxicity Test, all mice were observed daily for any clinical signs of systemic toxicity or local irritation at the application site. Both ears of each mouse were observed for erythema and scored according to OECD Guidelines for Testing of Chemicals No. 404, Table 2 [3]. Ear thickness was also measured using a thickness gauge on Day 1 (pre-dose), Day 3 (before treatment, approximately 48 hours after the first dose) and Day 6. Additional quantification of the ear thickness was performed by ear punch weight determination after the euthanasia of the experimental animals.
During the Preliminary Irritation / Toxicity Tests, signs of systemic toxicity (slight to severe decrease of activity (5 out of 5 animals) and hunched back (4 out of 5 animals)) followed by mortality was observed in the 25, 10 % (w/v) (2 out of 2 animals, respectively), and in the 5 % (w/v) dose group (1 out of 2 animals). All surviving animals were symptom free. Clinical observations are summarized in Table 8 of Appendix 3 and Table 11 of Appendix 4.
No marked body weight loss (>5% reduction of body weight) was observed in any of the surviving animals at Day 6 (3 days after the last treatment) in the preliminary study (Table 6 of Appendix 3 and Table 9 of Appendix 4).
Ear thickness of the animals was measured by using a thickness gauge on Days 1, 3 and 6, and by ear punch weight determination after the euthanasia of the experimental animals on Day 6. The ear thickness values and the weights of the ear punches (2 per animal) are summarized in Table 7 of Appendix 3 and Table 10 of Appendix 4.
The ear thickness values on Day 6 were more than 25 % higher compared to Day 1 for the one surviving animal at the 5 % (w/v) dose group, and for both animals at the 2.5 % (w/v) dose group. Ear punch weights in the surviving animals were elevated, but were within the acceptable range.
The draining auricular lymph nodes of the animals were visually examined: they were larger than normal in the surviving 5 % (w/v) animal and in the 2.5 % (w/v) dose group; and normal in the 1 % (w/v) dose group (subjective judgement by analogy with observations of former experiments).
Based on these results, 2.5 % (w/v) dose is selected as top dose for the main test.
Topical application
During the assay, each mouse was topically dosed on the dorsal surface of each ear with 25 µL of the appropriate formulation applied using a pipette. Each animal was dosed once a day for three consecutive days (Days 1, 2 and 3). Formulations were stirred from preparation up until the treatment such that samples taken for dosing were homogenous There was no treatment on Days 4, 5 and 6.
OBSERVATIONS
Clinical Observations
During the study (Day 1 to Day 6) each animal was observed daily for any clinical signs, including local irritation and systemic toxicity. Clinical observations were performed twice a day (before and after treatment) on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Individual records were maintained.
PROLIFERATION ASSAY
Injection of Tritiated Thymidine (3HTdR)
On Day 6, animals were taken to the radioactive suite and each mouse was intravenously injected via the tail vein with 250 µL of sterile PBS (phosphate buffered saline) containing approximately 20 µCi of 3HTdR using a gauge 25G x 1" hypodermic needle with 1 mL sterile syringe. Once injected, the mice were left for 5 hours (± 30 minutes).
Removal and Preparation of Draining Auricular Lymph Nodes
Five hours (±30 minutes) after intravenous injection the mice were euthanized by asphyxiation with ascending doses of carbon dioxide (deep anaesthesia was confirmed before making incision, death was confirmed before discarding carcasses).
The draining auricular lymph nodes were excised by making a small incision on the skin between the jaw and sternum, pulling the skin gently back towards the ears and exposing the lymph nodes. The nodes were then removed using forceps. The carcasses were discarded after cervical dislocation or after cutting through major cervical blood vessels.
Once removed, the nodes of mice from each test group was pooled and collected in separate Petri dishes containing a small amount (1-2 mL) of PBS to keep the nodes wet before processing.
Preparation of Single Cell Suspension of Lymph Node Cells
A single cell suspension (SCS) of pooled lymph node cells (LNCs) was prepared and collected in disposable tubes by gentle mechanical disaggregating of the lymph nodes through a cell strainer using the plunger of a disposable syringe. The cell strainer was washed with PBS (up to 10 mL). Pooled LNCs were pelleted with a relative centrifugal force (RCF) of 190 x g (approximately) for 10 minutes at 4 C.
After centrifugation supernatants were discarded. Pellets were gently resuspended and 10 mL of PBS was added to the tubes. The washing step was repeated twice. This procedure was repeated for each group of pooled lymph nodes.
Determination of Incorporated 3HTdR
After the final washing step, samples were centrifuged and supernatants were removed. Pellets were gently resuspended and 3 mL of 5 % (w/v) TCA solution was added to the tubes for precipitation of macromolecules.
After overnight (approximately 18 hours) incubation at 2-8 °C, precipitations were centrifuged (approximately 190 x g for 10 minutes at 4oC), and supernatants were removed. Pellets were resuspended in 1 mL of 5 % (w/v) TCA solution and dispersed by using an ultrasonic bath. Samples were transferred into a suitable sized scintillation vial filled with 10 mL of scintillation liquid and thoroughly mixed. The vials were loaded into a β-scintillation counter and 3HTdR incorporation was measured (10-minute measurement).
The β-counter expresses the 3HTdR incorporation as the number of radioactive disintegrations per minute (DPM). Background level was also measured in duplicates by adding 1 mL of 5 % (w/v) TCA solution into a scintillation vial filled with 10 mL of scintillation liquid.
USE OF RADIOACTIVE MATERIALS
Use of radioactive materials was recorded in the appropriate register. Regular decontamination of the working area with a verification of decontamination was carried out. Radioactive waste materials were processed according to normal laboratory standards. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
- Positive control results:
- No mortality, cutaneous reactions or signs of toxicity were observed in the positive control group. A significant lymphoproliferative response (stimulation index value of 8.6) was noted for a-Hexylcinnamaldehyde in this experiment. The results of the positive control group demonstrated the appropriate performance of the assay.
The observed mean DPN values for the negative and positive control were within the historical control range. Historical control data for the positive and negative control substances
In vivo (LLNA)
Results
- Key result
- Parameter:
- EC3
- Remarks on result:
- not determinable because of methodological limitations
- Cellular proliferation data / Observations:
- Appearance of the lymph nodes were larger than normal in the 2.5, 1 % (w/v) dose groups, in 2 out of 4 animals in the 0.5 % (w/v) dose group, and in the positive control group. Slightly larger than normal lymph nodes were observed in 2 out of 4 animals of the 0.5 % group and in all animals of the 0.25 % (w/v) dose group. Normal lymph nodes were observed in the negative control group.
The data show the test item is conclusively positive in this assay, however the poor dose response at the lower concentrations prevents an estimate of the EC3 being extrapolated.
The EC3 could not be calculated from the data but was clearly below 2.5% (w/v ).
Any other information on results incl. tables
CLINICAL OBSERVATION
No mortality or systemic toxicity was observed during the main study. Test item precipitate or minimal test item precipitate was present on the ears of the animals in the 2.5, and 1.0 % (w/v) groups (4 out of 4 animals, respectively).
BODY WEIGHT MEASUREMENT
No treatment related effects were observed on the mean body weight of the main study groups.
Individual Body Weights for all Animals with Group Means
Animal Number |
Identity Number |
Test Group Name |
Initial Body Weight (g) |
Terminal Body Weight* (g) |
Change# (%) |
5768 |
1 |
Negative (vehicle) control(in AOO) |
19.2 |
19.8 |
3.1 |
5772 |
2 |
18.7 |
18.3 |
-2.1 |
|
5781 |
3 |
18.4 |
19.2 |
4.3 |
|
5784 |
4 |
18.8 |
19.1 |
1.6 |
|
|
|
Mean |
18.8 |
19.1 |
1.7 |
5773 |
5 |
Selenium Disulphide |
19.6 |
20.2 |
3.1 |
5766 |
6 |
19.4 |
19.0 |
-2.1 |
|
5782 |
7 |
18.3 |
17.9 |
-2.2 |
|
5774 |
8 |
18.3 |
19.5 |
6.6 |
|
|
|
Mean |
18.9 |
19.2 |
1.3 |
5780 |
9 |
Selenium Disulphide |
19.5 |
20.0 |
2.6 |
5767 |
10 |
18.1 |
19.0 |
5.0 |
|
5779 |
11 |
18.8 |
19.1 |
1.6 |
|
5788 |
12 |
18.5 |
19.1 |
3.2 |
|
|
|
Mean |
18.7 |
19.3 |
3.1 |
5778 |
13 |
Selenium Disulphide 0.5 (w/v) % (in AOO) |
19.5 |
19.3 |
-1.0 |
5770 |
14 |
18.9 |
19.5 |
3.2 |
|
5783 |
15 |
18.2 |
18.6 |
2.2 |
|
5771 |
16 |
18.4 |
18.5 |
0.5 |
|
|
|
Mean |
18.8 |
19.0 |
1.2 |
5777 |
17 |
Selenium Disulphide 0.25 (w/v) % (in AOO) |
19.2 |
19.4 |
1.0 |
5769 |
18 |
19.3 |
19.5 |
1.0 |
|
5785 |
19 |
18.7 |
20.0 |
7.0 |
|
5789 |
20 |
18.7 |
19.3 |
3.2 |
|
|
|
Mean |
19.0 |
19.6 |
3.1 |
5776 |
21 |
Positive control (25% (w/v) HCA in AOO) |
19.6 |
20.0 |
2.0 |
5786 |
22 |
18.7 |
18.9 |
1.1 |
|
5787 |
23 |
18.1 |
18.9 |
4.4 |
|
5775 |
24 |
18.2 |
18.8 |
3.3 |
|
|
|
Mean |
18.7 |
19.2 |
2.7 |
Notes:
1. *: Terminal body weights were measured on Day 6.
2. #: = (Terminal Body Weight – Initial Body Weight) x 100 / Initial Body Weight
DPN and Stimulation Index Values for all Groups
Test Group Name |
Measured |
DPM |
No. of |
DPN |
Stimulation |
Background (5 (w/v) % TCA) |
41 |
- |
- |
- |
- |
Negative control (AOO) |
3392 |
3351.0 |
8 |
418.9 |
1.0 |
Selenium Disulphide |
22113 |
22072.0 |
8 |
2759.0 |
6.6 |
Selenium Disulphide |
21545 |
21504.0 |
8 |
2688.0 |
6.4 |
Selenium Disulphide |
15103 |
15062.0 |
8 |
1882.8 |
4.5 |
Selenium Disulphide |
18376 |
18335.0 |
8 |
2291.9 |
5.5 |
Positive control |
28972 |
28931.0 |
8 |
3616.4 |
8.6 |
INTERPRETATION OF OBSERVATIONS
The test item was a powder, which was formulated in AOO. There were no confounding effects of irritation or systemic toxicity at the applied concentrations, the proliferation values obtained are considered to reflect the potential of the test item to cause lymphoproliferation in the Local Lymph Node Assay. The resulting stimulation indices observed under these exaggerated test conditions were considered to be evidence that Selenium Disulphide caused lymphoproliferation, and the size of lymph nodes were in good correlation with this conclusion.
The data show the test item is conclusively positive in this assay, however the poor dose response at the lower concentrations prevents an estimate of the EC3 being extrapolated.
The EC3 could not be calculated from the data but was clearly below 2.5% (w/v ).
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The weight of evidence approach to the assessment of selenium disulphide utilising human monitoring data, selenium read-across substances and literature review; SeS2 cannot be regarded as a skin senstiserbased on the LLNA study conducted. The insolubility of the SeS2 does not allow for accurate and reliable LLNA studies to be performed as it gives rises to non-homogenous suspensions, in as such the LLNA study which was conducted is predicted to be a false positive.
- Executive summary:
The weight of evidence approach to the assessment of selenium disulphide utilising human monitoring data, selenium read-across substances and literature review; SeS2 cannot be regarded as a skin sensitiser based on the LLNA study conducted. The insolubility of the SeS2 does not allow for accurate and reliable LLNA studies to be performed as it gives rises to non-homogenous suspensions, in as such the LLNA study which was conducted is predicted to be a false positive.
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.