Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not applicable
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test substance: CdTe supplied by 5N Plus Inc (Montreal, Canada)
Appearance: Solid (powder > 75m)
Color: Black
Storage Conditions: Keep in a tightly sealed container in a cool, well-ventilated area, away from acid
Groups 1 and 2: Batch Number: 76337 ; Receipt Date: 27 March 2008, Production Date: March 2008, Expiry Date: September 2008
Group 3: Batch Number: 77481; Receipt Date: 07 May 2008, Production Date: 21 April 2008, Expiry Date: 13 November 2008

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (Europe)Laboratories Inc. (TOXI-COOP KFT, 1103 Budapest, Hungary)
- Weight at study initiation (g): 224-299
- Housing: in groups of 5, by sex, in solid-floor cages (Type III) with stainless steel mesh lids and softwood flake bedding.
- Diet: ssniff SM R/M-Z+H “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest,
Germany)
- Water: tap water, as for human consumption, ad libitum.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours of continuous artificial light in each twenty-four hour period.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Solid Aerosol Generator (SAG 410) (TOPAS GmbH, D-01279 Dresden, Germany) (for group 1) and a rotating brush powder disperser (Palas GmbH, Karlsruhe, Germany) and compressed air (for group 2 and 3)
- Method of holding animals in test chamber: the animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal‟s nases to enter the exposure port.
- Source and rate of air: Compressed air was supplied by means of an oil-free compressor and passed through a suitable filter system prior to introduction to the dust generator. The aerosol generated was supplied, using suitable tubing, to a glass particle-size separation (sedimentation) device before entering the exposure system (for group 1). The compressed air was supplied by an oil-less compressor and passed through respiratory quality filters and condensate traps prior to use. The aerosol generated was supplied, using suitable tubing, to a glass particle-size separation (sedimentation) device before entering the exposure system (for group 2 and 3)
- Method of particle size determination:
determined three times during the exposure period using a 7-stage impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany). Such devices employ an inertial separation technique to isolate particles in the discrete aerodynamic size ranges. Samples were taken from an unoccupied exposure port (representing the animal‟s breathing zone). The collection substrates and the backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by difference. The total amount collected for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 0.33, 0.5, 0.77, 1.21, 1.93, 3.13 and 5.09 m was calculated. From these data, using software supplied with the impactor (TSE Systems GmbH, Bad Homburg, Germany), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation were calculated. In addition, the proportion (%) of aerosol less than 4m (considered to be the respirable portion) was determined.
- Temperature, humidity, pressure in air chamber: monitored continuously and recorded every minute during each exposure period by the TSE-DACO monitoring system integrated into the exposure system:


TEST ATMOSPHERE
- Brief description of analytical method used: The test atmosphere was sampled at regular intervals during each exposure period. Samples were taken from an unoccupied exposure port (representing the animal‟s breathing zone) by pulling a suitable, known volume of test atmosphere through weighed GF10 glass fibre filters (Schleicher & Schuell GmbH, Dassel, Germany or similar).
- Samples taken from breathing zone: yes


Animal exposure system:
The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises of two, concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports. The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal‟s nares to enter the exposure port. After passing through the animal‟s breathing zone, spent aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
group 1: 5,73 mg/L
group 2: 1,07 mg/L
group 3: 3,03 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality/viability: once daily during the acclimatisation phase, once before exposure on the day of exposure (test day1), once per hour during exposure, once after exposure on test day 1, and twice daily during the remainder of the observation period
body weights: recorded on test datys 1 (before exposure), 4, 8 and 15 (day of necroscopy) using a Mettler PM 4000 balance
clinical signs: once per hour during exposure (only grosly abnormal signs, as the animals were in restraint tubes), once after exposure on test day 1, and once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
log/probit method: to calculate the median lethal concentration values and 95% confidence intervals

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.71 mg/L air
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
2.53 mg/L air
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
2.87 mg/L air
Exp. duration:
4 h
Mortality:
The total deaths were respectively 10/10, 0/10 and 7/10 for group 1, 2 and 3
Clinical signs:
Wet fur and fur staining on various occasions were commonly recorded both during and for several hours after exposure. These observations were considered to be related to the restraint and exposure procedures and, in isolation, are considered not to be biologically significant.
Very similar observations were recorded amongst the dose groups despite the range of concentration tested. During exposure, laboured respiration and/increased respiratory rate were noted; these observations were present on removal from restraint and, in general for surviving animals, persisted throughout the observation period. In addition, emaciation was noted in many survivors from Day 2 onwards and there was instance of lethargy.
Body weight:
The majority of surviving animals (9/13) during the observation period showed strong bodyweight losses, especially in the first week of the observation period.
Gross pathology:
Necroscopy:
Amongst animals that died during the course of the study, the following abnormalities were detected:
Lungs: dark red, edemic;
Trachea: foamy content;
Liver: congestion;
Kidneys: pale;
Intestines: empty;
Tracheobronchial lymph nodes: enlarged
Spleen: enlarged.
In the dead animals the alteration found in the lungs and in the liver (congestion) can be in connection with an acute circulatory insufficiency.
Amongst animals necropsied at terminal kill, the following macroscopic abnormalities were recorded:
Lungs – dark red, edemic, greyish-green colored areas;
Trachea: foamy content;
Kidneys: one-side pyelectasis;
Tracheobronchial lymph nodes: enlarged (bean sized), greyish-green colored;
Spleen: enlarged;
Uterus: slight hydrometra (in female animlas);
Nourishment: undernourishment;
Liver: congestion
In the surviving animals the hydrometra and the pyelectasis in an alteration with sporatic occurrence in experimental rats without toxicological meaning.
The alteration (dead and surviving animals too) found in the trachea, in the lungs (edemic, discoloration), in the tracheobronchial lymph nodes can be in connection with the effect of the test item. Macroscopic alteration in connection with the effect of the test item (CdTe) was found in the lungs and in the tracheobronchial lymph nodes.
Other findings:
none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Tests done according to standard protocol. Good quality and considered useful for setting the reference value for acute inhalation toxicity (LC50, 4h=2.7mg/L)
Executive summary:

The purpose of this study was to assess the acute inhalation toxicity of CdTe when administered to rats for a single continuous 4 -hour period, followed by an observation period of 14 days.

The acute inhalation median lethal concentrations (4hr LC50) (and 95% confidence limits) of CdTe, in Wistar Crl:(WI) BR strain rats, were calculated to be: All animals: 2.71 mg/L; Male only: 2.53 mg/L; Female only: 2.87 mg/L