Registration Dossier

Administrative data

Description of key information

Acute Toxicity via Oral Route

Key value determined in a GLP accredited laboratory study using acute toxic class method , in accordance with OECD GUIDELINES FOR TESTING OF CHEMICALS (420, adopted at 17th Dec. 2001), Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.bis. and EPA Health Effects Test Guidelines (OPPTS 870.1100), United States, EPA 712-C-98-190 (1998).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 October 2017 to 27 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
see "Any other information on materials and methods incl. tables" for further details.
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
see "Any other information on materials and methods incl. tables" for further details.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
see "Any other information on materials and methods incl. tables" for further details.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI Wistar rats
Sex:
female
Details on test animals and environmental conditions:
EXPERIMENTAL ANIMALS
Species and strain: Crl:WI Wistar rats
Source: Charles River Laboratories, Research Models and
Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
Hygienic level at arrival: SPF
Hygienic level during the study:Standard housing conditions
Number of animals: 6 animals
Sex: Female, nulliparous and non-pregnant
Age of animals at dosing: Young healthy adult rats, 9-10 weeks old
Body weight at treatment: 212 - 247 g
Acclimatisation period: At least 12 days

Husbandry
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Housing: Sighting studies: 1 animal (individual caging)
Main Study: 4 animals (group caging)
Cage type: Type II. polypropylene/polycarbonate
Bedding: Lignocel 3/4-S Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH + CO.KG (D-73494
Rosenberg, Germany) was available to animals during the study. Copy of the Certificate of Analysis is retained in the archive at Citoxlab Hungary Ltd.
Nesting: Arbocel crinklets natural produced by J. Rettenmaier & Söhne GmbH + CO.KG (D-73494 Rosenberg, Germany) was available to animals during the study. Copy of the Certificate of Analysis is retained in the archive at Citoxlab Hungary Ltd.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20.2 – 23.3 °C
Relative humidity: 33 – 80 %
Ventilation: 15-20 air exchanges/hour
Enrichment: Animals were housed by group, “except for sighting study as single animal was used”, to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
The temperature and relative humidity were recorded twice daily during the acclimatisation period and throughout the study.

Food and Water Supply
Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest,
Germany (Batch number: 262 21592, Expiry date: 31 January 2017), ad libitum, and tap water from the municipal supply, as for human consumption from a 500 ml bottle, ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József Attila u. 36., Hungary).
The quality control results are retained in the archives at Citoxlab Hungary Ltd.

Animal Identification
Animals were individually identified using numbers written on the tail with an indelible marker pen. The numbers were given on the basis of Citoxlab Hungary Ltd.' s Master File, for each animal allocated to the treatment groups. The cages were identified by cards, with information about study code, sex, dose group, cage number and individual animal numbers.
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
Formulation
Test item was powdered into fine dust and was freshly formulated at concentrations of 30 or 200 mg/mL in the vehicle, in the Pharmacy of Citoxlab Hungary Ltd. on the day of administration. The formulations were stirred with a magnetic stirrer up to finishing the treatment.

Vehicle information:
Name: 1 % Methyl cellulose
Dispense code: S11138
Manufacturer: Citoxlab Hungary Ltd.
Expiry Date: 22 October 2017
Storage condition: Refrigerated

The 1 % Methyl cellulose solution was prepared from Methyl cellulose powder produced by Shin-Etsu Chemical Co., Ltd. (Batch number: 5115851, Expiry date: 27 November 2018) and distilled water produced by Hungaro-Gal Kft. (Batch number: 8080617, Expiry date: 06 December 2017)

Justification of the dose:
The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. Based on the information provided by the Sponsor, 300 mg/kg bw was selected to be the starting dose.
Initially, in the sighting study, one female was treated at the dose level of 300 mg/kg bw. As no mortality was observed, one female was treated at the dose level of 2000 mg/kg bw. As no mortality was observed, the main study was conducted with four animals treated at the same dose level. No mortality was observed in the main study; therefore, no further testing was required according to OECD 420 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.bis.

A constant dosing volume of 10 mL/kg bw was used for all animals in both the sighting and main studies.

Procedure
A single oral gavage administration was followed by a fourteen-day observation period. On the day before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.
Doses:
Preliminary study: 300 mg/kg bw and 2000 mg/kg bw
Main study: 2000 mg/kg bw
No. of animals per sex per dose:
Preliminary study 1 animal was dosed with 300 mg/kg bw and and another with 2000 mg/kg bw
Main study: 4 animals were dosed with 2000 mg/kg bw
Control animals:
no
Details on study design:
Clinical Observations
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weight Measurement
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and on Day 7 and Day 14 (before necropsy).

NECROPSY
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%; Lot No.: 1609291-03, Expiry date: 31 October 2019, produced by: Alfasan International B.V., Kuipersweg 9, 3449 JA Woerden, The Netherlands; and Euthasol 400 mg/ml, Lot No.: 16B095, Expiry date: 31 January 2019, produced by: Produlab Pharma B.V., Forellenweg 16, 4941 SJ Raamsdonksveer, The Netherlands). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.

EVALUATION OF THE RESULTS
The method used was not intended to allow the calculation of a precise LD50 value. The test item was ranked into categories of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 420.

Clinical signs, body weight, body weight gain and gross macroscopic data were tabulated.
Preliminary study:
Initially, in the preliminary study, one female was treated at the dose level of 300 mg/kg bw. As no mortality was observed, one female was treated at the dose level of 2000 mg/kg bw, to which no mortality occurred.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
Cadmium selenide did not cause mortality in the study.
Clinical signs:
All treated animals were symptom-free during the observation period.
Body weight:
Body weight gains of Cadmium selenide treated animals during the study showed no indication of a treatment-related effect.
Gross pathology:
There was no evidence of any macroscopic changes in the surviving rats at the dose levels of 300 and 2000 mg/kg bw.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test item Cadmium selenide was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.
Executive summary:

The single-dose oral toxicity study with Cadmium selenide was performed according to the acute toxic class method (OECD 420 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.bis) in Crl:WI Wistar female rats.

Initially, in the sighting study, one female was treated at the dose level of 300 mg/kg bw. As no mortality was observed, one female was treated at the dose level of 2000 mg/kg bw. As no mortality was observed, the main study was conducted with four animals treated at the same dose level. No mortality was observed in the main study; therefore, no further testing was required according to OECD 420 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.bis.

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in 1% Methylcellulose aqueous solution at a concentration of 30 or 200 mg/mL at a dosing volume of 10 mL/kg bw.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and Day 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.

Mortality

Cadmium selenide did not cause mortality in the study.

Clinical observations

All treated animals were symptom-free during the observation period.

Body weight and body weight gain

Body weight gains of Cadmium selenide treated animals during the study showed no indication of a treatment-related effect.

Macroscopic Findings

There was no evidence of any macroscopic changes in the rats at the dose levels of 300 and 2000 mg/kg bw.

Conclusion:

Under the conditions of this study, the acute oral LD50 value of the test item Cadmium selenide was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.

According to Regulation (EC) 1272/2008 Cadmium selenide is not classified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
K1 - Study performed in GLP accredited laboratory to recognised OECD, EU & EPA standards.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Toxicity via Oral Route

The single-dose oral toxicity study with Cadmium selenide was performed according to the acute toxic class method (OECD 420 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.bis) in Crl:WI Wistar female rats.

Initially, in the sighting study, one female was treated at the dose level of 300 mg/kg bw. As no mortality was observed, one female was treated at the dose level of 2000 mg/kg bw. As no mortality was observed, the main study was conducted with four animals treated at the same dose level. No mortality was observed in the main study; therefore, no further testing was required according to OECD 420 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.bis.

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in 1% Methylcellulose aqueous solution at a concentration of 30 or 200 mg/mL at a dosing volume of 10 mL/kg bw.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and Day 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.

Mortality

Cadmium selenide did not cause mortality in the study.

Clinical observations

All treated animals were symptom-free during the observation period.

Body weight and body weight gain

Body weight gains of Cadmium selenide treated animals during the study showed no indication of a treatment-related effect.

Macroscopic Findings

There was no evidence of any macroscopic changes in the rats at the dose levels of 300 and 2000 mg/kg bw.

Justification for classification or non-classification

Acute Toxicity via Oral Route

Under the conditions of this study, the acute oral LD50 value of the test item Cadmium selenide was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats. According to Regulation (EC) 1272/2008 Cadmium selenide is not classified for acute oral toxicity.