Registration Dossier
Registration Dossier
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EC number: 215-148-3 | CAS number: 1306-24-7
Endpoint summary
Administrative data
Description of key information
The read across for Cadmium selenide (CAS: 1306-24-7 / EC: 215-148-3); is based upon the analogous substances to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of skin sensitisation. Based on the information available for the read across substances, the substance is not expected to be a skin sensitiser.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2012-06-20 to 2012-06-26
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: ELEVAGE JANVIER; Route des Chènes Secs B.P. 4105; 53940 LE GENEST-ST-ISLE, France
- Age at study initiation: 10 weeks
- Weight at study initiation: 20.5 – 22.6 g
- Housing: Group caging - mice were provided with glass tunneltubes; Type II. polypropylene/ polycarbonate
- Diet (e.g. ad libitum): ssniff SM R/M-Z+H Autoclavable complete diet for rats and mice - ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply from 500 ml bottle, ad libitum.
- Acclimation period: 19 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15-20 air exchange/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily light
IN-LIFE DATES: From: To: - Vehicle:
- propylene glycol
- Concentration:
- preliminary experiment: 100, 50, 10, 5, 2.5, 1, 0.5 and 0.1 % (w/v)
main experiment: 1, 0.5 and 0.1 % (w/v) - No. of animals per dose:
- Preliminary experiment: 2 females per group
Main experiment: 4 females per group - Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: examined in a short Preliminary Compatibility Test; the formulation (suspension) using Propylene glycol (PG)
as vehicle was suitable for the test.
- Irritation: ear thickness and the revealing ear punch weights were determinded, on day 1,3 and 6
- Lymph node proliferation response: not assessed, according to guideline
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Determination of cellular proliferation; incorporation of ³H-methyl thymidine is measured by β-scintillation counting as
disintegrations per minute (DPM).
- Criteria used to consider a positive response: A stimulation index of 3 or greater is an indication of a positive result.
TREATMENT PREPARATION AND ADMINISTRATION:
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). There was no treatment on Days 4, 5 and 6. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Positive control results:
- A significant lymphoproliferative response (stimulation index value of 12.8) was noted for the positive control chemical and this result confirmed
the validity of the assay. - Key result
- Parameter:
- SI
- Value:
- 3.2
- Test group / Remarks:
- 0.5 % (w/v)
- Key result
- Parameter:
- SI
- Value:
- 2
- Test group / Remarks:
- 0.25 % (w/v)
- Key result
- Parameter:
- SI
- Value:
- 2.1
- Test group / Remarks:
- 0.1 % (w/v)
- Interpretation of results:
- ambiguous
- Conclusions:
- Under the conditions of the present assay Sodium selenite was shown to have a sensitization potential (sensitizer) in the Local Lymph Node Assay, according to study author. However, the positive response at the highest concentration was slight and metals are known to have a lower predictivity in the LLNA than organic molecules.
- Executive summary:
In an OECD Guideline 429 study (Skin Sensitisation: Local Lymph Node Assay), groups of four female CBA/J Rj mice were treated with 1, 0.5, 0.25 and 0.1% (w/v) Sodium selenite in PG.
The solutions of the test item were applied on the dorsal surface of ears of experimental animals (25 μl/ear) for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. On Day 6, the cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).
The highest dose group of 1% (w/v) was excluded from the evaluation as during the experiment one animal was found dead on Day 4. The guideline requires the maximum dose to have no systemic toxicity and 4 animals alive, these criteria were not met.
No mortality, signs of systemic toxicity or body weight loss were observed during the study for the remaining three dose groups. No treatment related effects were observed on animal body weights in any treated groups. Very slight erythema (score 1) was observed in 1 % (w/v) test item treated group animals on Day 3 and in one or two animals in positive control group on Days 2 and 3.
Stimulation index values of the test item were 3.2, 2.0 and 2.1 at treatment concentrations of 0.5, 0.25 and 0.1% (w/v), respectively.
A significant lymphoproliferative response (stimulation index value of 12.8) was noted for the positive control (α-Hexylcinnamaldehyde (25% (w/v) dissolved in PG)), which confirmed the validity of the assay.
According to study author, under the conditions of the present assay Sodium selenite (Batch No.: 114307) tested in Propylene Glycol as vehicle, was shown to have a sensitization potential (sensitizer) in the Local Lymph Node Assay. However, the positive response at the highest concentration was slight and metals are known to have a lower predictivity in the LLNA than organic molecules.
However, the following factors were not taken into account by the study author:
- The substance Sodium selenite is dermally relatively toxic
- Inflammatory processes might be a possible confounding factor for a false positive result
- The effect on ear weights as observed in the preliminary range finding study were not considered as possible irritation by the study authors.
Further discussion is outlined in the endpoint summary.
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2010-03-18 to 2010-04-29
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- , 20002-04-24
- Deviations:
- yes
- Remarks:
- modified OECD 429 ,method according to Ehlings et al. 2005
- Principles of method if other than guideline:
- The test was performed in accordance with the method according to Ehling et al (2005): An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: first round, Toxicology 212 (2005) 60-68 and Ehling et al (2005): An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round, Toxicology 212 (2005) 69-79.
Threshold values of the stimulation indices of lymph node cell count and ear weight were calculated by dividing the average values per group of the test item treated animals by the vehicle treated ones. Values above 1.4 (cell count) or 1.1 (ear weight) are considered positive
(these values were fixed empirically during the inter-laboratory validation of this method). In addition, the lymph node weights were determined for concentration related properties. - GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2009-11-12
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks
- Weight at study initiation: 20 - 26 g
- Housing: The animals were kept singly in MAKROLON cages (type III) with a basal surface of approx. 39 cm x 23 cm and a height of approx. 15 cm; Granulated textured wood Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet (ad libitum): Commercial diet ssniff® R/M-H V1534 served as food (ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water (ad libitum): tap water
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Air changes: 12 - 18 times per hour.
- Photoperiod (hrs dark / hrs light): 12 / 12
No further information on the test animals was stated. - Vehicle:
- other: acetone/olive oil (3 + 1, v/v)
- Concentration:
- 0.25 %, 0.5 %, 1.0 %, and 2.5 % of zinc selenite (w/w)
- No. of animals per dose:
- 6 female mice
- Details on study design:
- RANGE FINDING TESTS:
A preliminary experiment was carried out in 21 animals to examine the systemic toxicity, the irritating potential and handling/application of the test item in order to select the appropriate concentrations. Six concentrations of 1% (3 animals), 2.5% (3 animals), 5% (3 animals), 10% (4 animals), 25% (4 animals) and 50% (4 animals) of zinc selenite in acetone/olive oil (3+1 v/v), w/w, were examined.
Results:
Concentrations of 5% or 10% cause mortality in one of 3 or 1 of 4 animals, respectively. All four of 4 animals treated with concentrations of 25% or 50%, respectively, died prematurely. No pronounced irritating properties were observed in this preliminary experiment at concentrations of 1.0 % or 2.5 %, and no difference in ear weight and ear thickness were noted.
Hence, for the main study concentrations of 0.25%, 0.5%, 1.0% or 2.5% were used.
MAIN STUDY
The test item was suspended in a mixture of acetone (Batch no. 90980, SIGMA ALDRICH Chemie GmbH, 82024 Taufkirchen, Germany) / olive oil (Batch nos. 4535401 and 4602602, Henry Lamotte GmbH, 28197 Bremen, Germany) (3 + 1), v/v).
The test item suspension was administered to the dorsum of both animal's ears at an application volume of 25 µL/ear.
The concentrations used in the main study were chosen based on the preliminary dose range finding.
The experimental schedule of the assay was as follows:
Day 1:
The weight of each animal was individually identified and recorded. In addition, ear swelling measurements were carried out at the helical edge of both ears using an Oditest micrometer.
Open application of 25 µL of the appropriate dilution of the test item, the vehicle alone or the positive control (as appropriate) were administered to the dorsum of each ear.
Days 2 and 3:
The application procedure carried out on day 1 was repeated.
Day 4 (24 hours after the last application the animals were sacrificed under ether anaesthesia by cutting the aorta abdominalis):
Ear swelling measurements (immediately before sacrificing the mice) were carried out at the helical edge of both ears using an Oditest micrometer.
Punch biopsies of 8 mm in diameter of the apical area of both ears were prepared and immediately weighed on an analytical balance.
Lateral pairs of auricular lymph nodes draining the ear tissue were excised, carefully separated from remaining fatty tissue and weighed on an analytical balance immediately following preparation. The lymph nodes were then stored on ice in PBS/0.5% BSA and subjected to the preparation of single cell suspensions by mechanical tissue disaggregation. The cells were counted automatically in a cell counter.
OBSERVATIONS:
The following observations were made during the course of the study:
- Clinical signs: Animals were observed once daily for any clinical signs of local systemic irritation at the application site or of systemic toxicity. Observations were recorded for each individual animal. Cageside observations included skin/fur, eyes, mucous membranes, respiratory and circulatory systems, somatomotor activity and behaviour patterns. The onset, intensity and duration of any signs observed were recorded.
In addition, animals were checked regularly throughout the working day from 7:30 a.m. to 4:30 p.m. On Saturdays and Sundays animals were checked regularly from 8:00 a.m. to 12:00 noon with a final check performed at approximately 4:00 p.m., if applicable.
- Body weight: The weight of each mouse was recorded at the time of allocation of animals to groups (test day 1) and at the time of necropsy (test day 4).
ANALYSIS OF RESULTS:
The so-called stimulation (or LLN-) indices to determine the sensitising potential were calculated by dividing the average absolute lymph node weight or lymph node cell counts per group of the test item treated animals by the vehicle treated ones.
Thus, in case of no stimulating effect the index for the lymph node cell count is always below 1.4 (cut-off value). An index above 1.4 is considered positive.
For lymph node weight significance at p≤ 0.01 is considered positive (U-test according to MANN and WHITNEY). A possible concentration-response-relationship for the lymph node weight in order to determine a possible sensitising potential was examined by linear regression analysis employing PEARSON's correlation coefficient. Outliers would have been determined according to the NALIMOV test.
In addition, the acute inflammatory skin reaction (irritating potential) was measured by ear weight determination of circular biopsies of the ears and ear thickness measurements on test day 1 and test day 4 to identify skin irritation properties of the test item employing the U-test according to MANN and WHITNEY by comparing the test groups to the vehicle control.
The stimulation indices were calculated by dividing the average ear weight and average ear thickness on test day 4 per group of the test item treated animals by the vehicle treated ones. The cut-off threshold value for ear weight was set at 1.1.
No further information on the study design was stated. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Please refer to "Details on study design (LLNA)"
- Positive control results:
- The positive control group caused the expected increases in lymph node cell count and lymph node weight (statistically significant at p ≤ 0.01). The values for the stimulation index of lymph node cell count and lymph node weight were 1.66 and 1.67, respectively. Therefore, the study could be regarded as valid.
- Key result
- Parameter:
- SI
- Value:
- 0.623
- Test group / Remarks:
- 0.25% w/w
- Remarks on result:
- other: cell count
- Key result
- Parameter:
- SI
- Value:
- 0.753
- Test group / Remarks:
- 0.25% w/w
- Remarks on result:
- other: lymph node weight
- Key result
- Parameter:
- SI
- Value:
- 0.861
- Test group / Remarks:
- 0.5 % w/w
- Remarks on result:
- other: cell count
- Key result
- Parameter:
- SI
- Value:
- 0.928
- Test group / Remarks:
- 0.5 % w/w
- Remarks on result:
- other: lymph node weight
- Key result
- Parameter:
- SI
- Value:
- 0.966
- Test group / Remarks:
- 1.0 % w/w
- Remarks on result:
- other: cell count
- Key result
- Parameter:
- SI
- Value:
- 1.052
- Test group / Remarks:
- 1.0 % w/w
- Remarks on result:
- other: lymph node weight
- Key result
- Parameter:
- SI
- Value:
- 0.408
- Test group / Remarks:
- 2.5 % w/w
- Remarks on result:
- other: cell count
- Key result
- Parameter:
- SI
- Value:
- 0.588
- Test group / Remarks:
- 2.5 % w/w
- Remarks on result:
- other: lymph node weight
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the present test conditions, zinc selenite at concentrations of 0.25 %, 0.5 %, 1.0 % and 2.5 % (w/w) in acetone/olive oil (3 +1, v/v) did not reveal any sensitising properties in the local lymph node assay.
According to the criteria specified by Regulation (EC) No.: 1272/2008. and subsequent regulations, the test item requires no classification as skin sensitiser. - Endpoint:
- skin sensitisation, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- 3 studies available for read-across
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- In accordance with Regulation (EC) 1907/2006 Annex XI (1.5) and the relevant ECHA guidance documents, the substances detailed in the table below are grouped for the purposes of read across to reduce the need for unnecessary repeat testing on the basis that the substances are similar on the basis of a common functional groups.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study. Telluroxocadmium (CAS: 1306-25-8 / EC: 215-149-9)
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study. Telluroxocadmium (CAS: 1306-25-8 / EC: 215-149-9)
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study. Telluroxocadmium (CAS: 1306-25-8 / EC: 215-149-9)
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study. Telluroxocadmium (CAS: 1306-25-8 / EC: 215-149-9)
- Key result
- Reading:
- other: Historical data
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 50%
- Clinical observations:
- discrete erythema
- Remarks on result:
- other: Score 0.70
- Remarks:
- Telluroxocadmium (CAS: 1306-25-8 / EC: 215-149-9)
- Key result
- Reading:
- other: Histrocial data
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 40%
- Clinical observations:
- discrete erythema
- Remarks on result:
- other: Score 0.40
- Remarks:
- Telluroxocadmium (CAS: 1306-25-8 / EC: 215-149-9)
- Key result
- Parameter:
- SI
- Value:
- 0.623
- Test group / Remarks:
- 0.25 % w/w
- Remarks on result:
- other: cell count
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 0.753
- Test group / Remarks:
- 0.25% w/w
- Remarks on result:
- other: lymph node weight
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 0.861
- Test group / Remarks:
- 0.5% w/w
- Remarks on result:
- other: cell count
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 0.928
- Test group / Remarks:
- 0.5% w/w
- Remarks on result:
- other: lymph node weight
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 0.966
- Test group / Remarks:
- 1.0 % w/w
- Remarks on result:
- other: cell count
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 1.052
- Test group / Remarks:
- 1.0 % w/w
- Remarks on result:
- other: lymph node weight
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 0.408
- Test group / Remarks:
- 2.5 % w/w
- Remarks on result:
- other: cell count
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 0.588
- Test group / Remarks:
- 2.5 % w/w
- Remarks on result:
- other: lymph node weight
- Remarks:
- Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 3.2
- Test group / Remarks:
- 0.5 % (w/v)
- Remarks on result:
- other: Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 2
- Test group / Remarks:
- 0.25 % (w/v)
- Remarks on result:
- other: Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Key result
- Parameter:
- SI
- Value:
- 2.1
- Test group / Remarks:
- 0.1 % (w/v)
- Remarks on result:
- other: Zinc selenite (CAS: 13597-46-1 / EC: 237-048-9)
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The read across for Cadmium selenide (CAS: 1306-24-7 / EC: 215-148-3); is based upon the analogous substances to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of skin sensitisation. Based on the information available for the read across substances, the substance is not expected to be a skin sensitiser.
- 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)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented and scientifically good . Tests done according to standard protocol.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Study was conducted in 2011
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: LAB-ÁLL Bt. Budapest, 1174 Hunyadi u. 7
- Age at study initiation: Young adult, 8 weeks
- Weight at study initiation: 344 – 386 g
- Housing: Animals were housed in macrolon cages, size III., with 2 or 3 animals/cage (42 x 42 x 19 cm)
- Diet ad libitum: PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary
- Water ad libitum: Animals received tap water from municipal supply as for human consumption, containing 50 mg/100 ml ascorbic acid,
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 – 25.3 °C
- Humidity (%): 30 – 70 %
- Air changes (per hr): 15-20 air exchange/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily from 6 a.m. to 6 p.m. (artificial light) - Route:
- intradermal and epicutaneous
- Vehicle:
- other: aqueous 1 % (w/v) Methylcellulose solution
- Concentration / amount:
- Intra-dermal Induction Exposure (MAIN study I): 0.1 % (w/v) CdTe in 1% methylcellulose
Dermal Induction Exposure (MAIN study II): 100% (w/v) CdTe in 1% methylcellulose
Challenge Exposure (MAIN study III): 100% (w/v) CdTe in 1% methylcellulose - Route:
- epicutaneous, occlusive
- Vehicle:
- other: aqueous 1 % (w/v) Methylcellulose solution
- Concentration / amount:
- Intra-dermal Induction Exposure (MAIN study I): 0.1 % (w/v) CdTe in 1% methylcellulose
Dermal Induction Exposure (MAIN study II): 100% (w/v) CdTe in 1% methylcellulose
Challenge Exposure (MAIN study III): 100% (w/v) CdTe in 1% methylcellulose - No. of animals per dose:
- test groups: 10
control group: 5 - Details on study design:
- RANGE FINDING TESTS:
*) For the intra-dermal treatment: the following formulations were applied:
-0.10 mL of the test item in 1 % methylcellulose at the 5, 1, 0.1 and 0.01 % (w/v) concentrations,
-0.10 mL of test item in 5, 1, 0.1 and 0.01 % (w/v) concentrations, formulated in a 1:1 (v/v) mixture of Freund's Adjuvant (FCA) and physiological saline (the test item was suspended in mixture of FCA and saline at concentrations of 10, 2, 0.2 and 0.02 % (w/v) and diluted with 1 % methylcellulose to the necessary concentrations).
It was found that 5 and 1 % (w/v) concentrations formulated with FCA and saline mixture are inapplicable due to the physical nature of the mixtures, therefore the 5 and 1 % (w/v) concentrations in 1 % methylcellulose were not tested during the preliminary test, since it will not be technically applicable for the main test.
*)For the dermal application: approximately 0.2 mL of the formulated test item in 1 % methylcellulose was applied at concentrations of 100, 75, 50 and 25 % (w/v) onto the clipped and shaved skin of the animals over an area of 4-6 cm2.
MAIN STUDY (cfr any other information on materials and methods)
A. INDUCTION EXPOSURE
a) intra-dermal induction exposure:
b) dermal induction exposure:
B. CHALLENGE EXPOSURE - Positive control substance(s):
- not required
- Remarks:
- The sensitivity and reliability of the experimental procedure is assessed twice a year by use of items which are known to have moderate skin sensitisation properties (eg 2-mercaptobenzothiazole. 2-mercaptobenzothiazole was classified as skin sensitizer.
- Positive control results:
- The sensitivity and reliability of the experimental procedure is assessed twice a year by use of items which are known to have moderate skin sensitisation properties such as 2-mercaptobenzothiazole.
Challenge with test item 2-Mercaptobenzothiazole resulted in a positive response in test animals sensitised previously. The net response values at the 24 and 48 hours observations represented an incidence rate of 50 % and 40 % and the net score values of 0.70 and 0.40 respectively. In the control animals no visible changes were found either at the 24 and 48 hours examinations or following challenge with the test item. The dermal scores represented discrete erythema developed on the skin of sensitised guinea pigs.
On the basis of these results , the test item 2-mercaptobenzothiazole was classified as skin sensitizer. - Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study.
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study.
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100% (w/v) CdTe in 1% methylcellulose
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No overt sign of an adverse clinical response to treatment with the test item during the course of the study
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% (w/v) CdTe in 1% methylcellulose . No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No overt sign of an adverse clinical response to treatment with the test item during the course of the study.
- Key result
- Reading:
- other: Historical data
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 50%
- Clinical observations:
- discrete erythema
- Remarks on result:
- other: Score 0.70
- Key result
- Reading:
- other: Histrocial data
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 40%
- Clinical observations:
- discrete erythema
- Remarks on result:
- other: Score 0.40
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of the present assay the test item Cadmium telluride (CdTe) (Batch No.: 138683) was shown to have no sensitisation potential and classified as a non-sensitizer, according to current EU-regulations.
- Executive summary:
A skin sensitisation study was performed in the guinea pig according to the Magnusson-Kligman method, using a maximisation method with Freund's complete adjuvant to evaluate the sensitisation potential of test item Cadmium telluride (CdTe).
Ten test animals were subjected to sensitisation procedures in a two-stage process, i.e. an intra-dermal treatment and a topical application. The test item was used at a concentration of 0.1 % (w/v) in 1 % methylcellulose for intra-dermal injections and at a concentration of 100 % (w/v) test item suspension in 1 % aqueous methylcellulose for dermal sensitisation treatment.Two weeks after the last induction exposure, a challenge dose (at a concentration of100 % (w/v) test item suspension in 1 % methylcellulose) was administeredon the left flank of animal.The right flank area of animals was treated with 50 % dilution with 1 % methylcellulose of the maximum dermal challenge dose as a safeguard dose.Challenge was performed by dermal application of the test item. Five control guinea pigs were simultaneously exposed to 1 % methylcellulose during the sensitisation phase I (intra-dermal treatment). During the sensitisation phase II (dermal treatment) the control animals were treated with1 % methylcellulose and they were treated with the test item at a concentration of 100 % (w/v) and 50 % (w/v) in1 % methylcellulose only during the challenge (phase III).
Incidence Rate:
No signs of contact sensitisation were detected in guinea pigs previously exposed to the test item during the experiments.
Intensity of Sensitisation Response:
In the control and treated animals the mean of the scores was 0.00 according to the 24 and 48-hour results.
In conclusion, under the conditions of the present assay the test item Cadmium telluride (CdTe)(Batch No.: 138683) was shown to have no sensitisation potential and classified as a non-sensitizer, according to current EU-regulations.
Referenceopen allclose all
The highest dose group of 1% (w/v) was excluded from the evaluation as during the experiment one animal was found dead on Day 4.
DPM, DPN and Stimulation Index Values for all Groups
Test Group Name |
Measured DPM/group |
Group DPM (background corrected) |
No. of Nodes |
DPN |
Stimulation Index Values |
Background (5 (w/v) % TCA ) |
35.5 |
|
- |
|
|
Negative control PG |
1079 |
1043.5 |
8 |
130.4 |
1.0 |
Sodium selenite 1% (w/v) in PG* |
2391 |
2355.5 |
6 |
392.6 |
3.0 |
Sodium selenite 0.5% (w/v) in PG |
3405 |
3369.5 |
8 |
421.2 |
3.2 |
Sodium selenite 0.25% (w/v) in PG |
2163 |
2127.5 |
8 |
265.9 |
2.0 |
Sodium selenite 0.1% (w/v) in PG |
2256 |
2220.5 |
8 |
277.6 |
2.1 |
Positive control 25 % HCA in PG |
13396 |
13360.5 |
8 |
1670.1 |
12.8 |
* Due to the mortality at 1% (w/v) makes this DPM data uninterpretable. The numbers are presented in the table, but are not used in study interpretation.
DPN = DPM divided by the number of lymph nodes
Individual ear thickness for all animals (preliminary test)
Animal Number |
Test Group Name |
Ear thickness on Day 1 (mm) |
Ear thickness on Day 3 (mm) |
Ear thickness on Day 6 (mm) |
Ear weight on Day 6 (mg) |
9375 |
100 (w/v) % |
0.23 / 0.23 |
|
|
|
9394 |
100 (w/v) % |
0.21 / 0.22 |
|
|
|
9430 |
50 (w/v) % |
0.22 / 0.22 |
|
|
|
9437 |
50 (w/v) % |
0.22 / 0.22 |
|
|
|
9441 |
10 (w/v) % |
0.20 / 0.20 |
|
|
|
9410 |
10 (w/v) % |
0.23 / 0.23 |
|
|
|
9545 |
5 (w/v) % |
0.23 / 0.22 |
|
|
|
9611 |
5 (w/v) % |
0.21 / 0.22 |
|
|
|
9616 |
2.5 (w/v) % |
0.20 / 0.21 |
|
|
|
9580 |
2.5 (w/v) % |
0.21 / 0.21 |
|
|
|
9426 |
1 (w/v) % |
0.23 / 0.24 |
0.23 / 0.23 |
0.26 / 0.27 |
24.4 |
9442 |
1 (w/v) % |
0.22 / 0.21 |
0.23 / 0.22 |
0.18 / 0.17 |
23.6 |
9445 |
0.5 (w/v) % |
0.22 / 0.21 |
0.23 / 0.23 |
0.26/ 0.24 |
23.6 |
9448 |
0.5 (w/v) % |
0.21 / 0.21 |
0.21 / 0.22 |
0.27 / 0.21 |
23.5 |
9379 |
0.1 (w/v) % |
0.21 / 0.20 |
0.25 / 0.22 |
0.22 / 0.22 |
13.8 |
9393 |
0.1 (w/v) % |
0.22/0.23 |
0.22/0.23 |
0.22/0.22 |
14.2 |
**: Based on the historical control data, the maximum normal weight is 21.1 mg. Positive response is over 26.3 mg.
Ear thickness of the animals was measured using by a thickness gauge on Days 1, 3 and 6 in survived animals. Additional quantification of the ear thickness was performed by ear punch weight determination after the euthanasia of the survived experimental animals. The ear thickness data and the revealing ear punch weights were within the historical control range in the 0.1 %(w/v) dose group. The ear thickness data on Day 6 in the 1 and 0.5 % (w/v) treated group animals were slightly higher than measured on Days 1 or 3, and the ear punch weights were also slightly higher than the normal range, but this was considered as a negative effect. Although these results could be an indication of irritation, there were no visible signs of any irritation, so the highest dose (1 %) was considered to be acceptable for the main test. In order to make sure that there will be three acceptable dose groups, an additional dose group was used in the main experiment.
Treatment with zinc selenite at concentrations of 0.25%, 0.5%, 1.0% and 2.5% did not reveal statistical significantly increased values for lymph node cell count. The stimulation indices of the lymph node cell count did not exceed the threshold level of 1.4. Hence, the test item is classified as not sensitising.
The threshold level for the ear weight of 1.1 was not exceeded and the lymph node weights were not increased in a dose-related way, i.e. no irritating properties were noted.
No signs of local or systemic intolerance were recorded.
The animal body weight was not affected by the treatment with concentrations up to 1.0% Zinc selenite. Treatment with a concentration of 2.5% revealed a reduction of body weight from the initial value (day 1) by 16.7% on test day 4. Lymph node cell count, ear weights and lymph node weights were reduced at all tested concentrations. These findings are probably caused by the toxic properties of the test item.
Main Study
A group of 10 animals was treated with the test item during the induction phase of the study. Injections were given intra-dermally with and without FCA (sensitisation phase I) and one week later the test item was applied dermally on the same site (sensitisation phase II). The animals were challenged by dermal exposure two weeks laterwith the test item at a concentration of 100 % (w/v) in 1 % methylcellulose.
Five control guinea pigs were simultaneously exposed to 1 % methylcellulose during the sensitisation phase I (intra-dermal treatment; with and without FCA). During the sensitisation phase II (dermal treatment) thecontrol animals were treated with1 % methylcellulose and theywere treated with the test item at a concentration of 100 % (w/v) in1 % methylcellulose only on the challenge day.
Skin Effects after the Challenge Exposure
Test group
After the challenge with the test item at a concentration of 100 % (w/v) in 1 % methylcellulose, no positive response was observed in the treated animals. The mean of the scores was 0.00 according to the 24 and 48-hours results. The right shaved flank area of all animals was treated with a test item concentration of 50 (w/v) % in 1 % methylcelluloseas a safeguardand no reaction was noted.
Control group
After the challenge with the test itemat a concentration of 100 % (w/v) in 1 % methylcellulose no visible changes were found at the 24 and 48 hours examinations. The right shaved flank area of control animals was treated with a test item concentration of 50 (w/v) % in 1 % methylcelluloseas a safeguard and no reaction was noted.
Clinical Observations
There were no overt signs of an adverse clinical response to treatment with the test item during the course of the study.
Mortality
There were no moribund or dead animals during the study.
Body Weight
The individual body weights of the guinea pigs were measured at the beginning and at the end of experiment. There were no notable differences between the test animal group and the control group.
Main Study
A group of 10 animals was treated with the test item during the induction phase of the study. Injections were given intra-dermally with and without FCA (sensitisation phase I) and one week later the test item was applied dermally on the same site (sensitisation phase II). The animals were challenged by dermal exposure two weeks laterwith the test item at a concentration of 100 % (w/v) in 1 % methylcellulose.
Five control guinea pigs were simultaneously exposed to 1 % methylcellulose during the sensitisation phase I (intra-dermal treatment; with and without FCA). During the sensitisation phase II (dermal treatment) thecontrol animals were treated with1 % methylcellulose and theywere treated with the test item at a concentration of 100 % (w/v) in1 % methylcellulose only on the challenge day.
Skin Effects after the Challenge Exposure
Test group
After the challenge with the test item at a concentration of 100 % (w/v) in 1 % methylcellulose, no positive response was observed in the treated animals. The mean of the scores was 0.00 according to the 24 and 48-hours results. The right shaved flank area of all animals was treated with a test item concentration of 50 (w/v) % in 1 % methylcelluloseas a safeguardand no reaction was noted.
Control group
After the challenge with the test itemat a concentration of 100 % (w/v) in 1 % methylcellulose no visible changes were found at the 24 and 48 hours examinations. The right shaved flank area of control animals was treated with a test item concentration of 50 (w/v) % in 1 % methylcelluloseas a safeguard and no reaction was noted.
Clinical Observations
There were no overt signs of an adverse clinical response to treatment with the test item during the course of the study.
Mortality
There were no moribund or dead animals during the study.
Body Weight
The individual body weights of the guinea pigs were measured at the beginning and at the end of experiment. There were no notable differences between the test animal group and the control group.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
A skin sensitisation study was performed in the guinea pig according to the Magnusson-Kligman method, using a maximisation method with Freund's complete adjuvant to evaluate the sensitisation potential of test item Cadmium telluride (CdTe).
Ten test animals were subjected to sensitisation procedures in a two-stage process, i.e. an intra-dermal treatment and a topical application. The test item was used at a concentration of 0.1 % (w/v) in 1 % methylcellulose for intra-dermal injections and at a concentration of 100 % (w/v) test item suspension in 1 % aqueous methylcellulose for dermal sensitisation treatment.Two weeks after the last induction exposure, a challenge dose (at a concentration of100 % (w/v) test item suspension in 1 % methylcellulose) was administeredon the left flank of animal.The right flank area of animals was treated with 50 % dilution with 1 % methylcellulose of the maximum dermal challenge dose as a safeguard dose.Challenge was performed by dermal application of the test item.Five control guinea pigs were simultaneously exposed to 1 % methylcellulose during the sensitisation phase I (intra-dermal treatment). During the sensitisation phase II (dermal treatment) the control animals were treated with1 % methylcellulose and they were treated with the test itemat a concentration of 100 % (w/v)and 50 % (w/v)in1 % methylcellulose only during the challenge (phase III).
Incidence Rate:
No signs of contact sensitisation were detected in guinea pigs previously exposed to the test item during the experiments.
Intensity of Sensitisation Response:
In the control and treated animals the mean of the scores was 0.00 according to the 24 and 48-hour results.
In conclusion, under the conditions of the present assay the test item Cadmium telluride (CdTe)(Batch No.: 138683) was shown to have no sensitisation potential and classified as a non-sensitizer, according to current EU-regulations.
Under the present test conditions, zinc selenite at concentrations of 0.25 %, 0.5 %, 1.0 % and 2.5 % (w/w) in acetone/olive oil (3 +1, v/v) did not reveal any sensitising properties in the local lymph node assay.
In an OECD Guideline 429 study (Skin Sensitisation: Local Lymph Node Assay), groups of four female CBA/J Rj mice were treated with 1, 0.5, 0.25 and 0.1% (w/v) Sodium selenite in PG.
The solutions of the test item were applied on the dorsal surface of ears of experimental animals (25 μl/ear) for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. On Day 6, the cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).
The highest dose group of 1% (w/v) was excluded from the evaluation as during the experiment one animal was found dead on Day 4. The guideline requires the maximum dose to have no systemic toxicity and 4 animals alive, these criteria were not met.
No mortality, signs of systemic toxicity or body weight loss were observed during the study for the remaining three dose groups. No treatment related effects were observed on animal body weights in any treated groups. Very slight erythema (score 1) was observed in 1 % (w/v) test item treated group animals on Day 3 and in one or two animals in positive control group on Days 2 and 3.
Stimulation index values of the test item were 3.2, 2.0 and 2.1 at treatment concentrations of 0.5, 0.25 and 0.1% (w/v), respectively.
A significant lymphoproliferative response (stimulation index value of 12.8) was noted for the positive control (α-Hexylcinnamaldehyde (25% (w/v) dissolved in PG)), which confirmed the validity of the assay.
According to study author, under the conditions of the present assay Sodium selenite (Batch No.: 114307) tested in Propylene Glycol as vehicle, was shown to have a sensitization potential (sensitizer) in the Local Lymph Node Assay. However, the positive response at the highest concentration was slight and metals are known to have a lower predictivity in the LLNA than organic molecules.
However, the following factors were not taken into account by the study author:
- The substance Sodium selenite is dermally relatively toxic
- Inflammatory processes might be a possible confounding factor for a false positive result
- The effect on ear weights as observed in the preliminary range finding study were not considered as possible irritation by the study authors.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the information available from the read-across substances, cadmium selenide does not meet the classification criteria for skin sensitisation according to Regulation (EC) 1272/2008
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