Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
August 2003- February 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented and corresponded to the requirements of the recommended Annex V test guidelines.
Justification for data waiving:
other:

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Litharge lead oxide
- Molecular formula (if other than submission substance): PbO
- Physical state: yellow solid powder
- Analytical purity: 99.8%
- Composition of test material, percentage of components: Pb3/Pb4 0.003%; metalic lead 0.01%; Cu 0.0001%; Fe 0.0008%
- Lot/batch No.: 210213
- Expiration date of the lot/batch: Until May 2005
- Expiration date of radiochemical substance (if radiolabelling): Until May 2005
- Storage condition of test material: At room temperature, in tightly closed container

Test animals

Species:
rat
Strain:
other: Charles River Deutschland GmbH - CD
Sex:
male/female
Details on test animals and environmental conditions:
Age at start of adaptation: males: approx. 45 days
females: approx. 56 days

Body Weight at start of administration males: 217-233 g
females: 195-211 g
Number 10 (5 male and 5 female animals)
Duration of experiment: at least 5 adaptation days, 1 test day and 2 recovery weeks

Diet - ssniff R/M-H V11534 served as food (ssniff Spezialdiaten GmbH, D-59494 Soest;composition: see Appendix 2). Feeding was discontinued approx. 16 hours before exposure; only tap water was ten available ad libitum. Periodic analysis of the food for contaminants based on EPA/USA is conducted at least twice a year by LUFA-ITL (limitation for contaminants in the diet: see Appendix 2). Certificates of analysis of the composition and
for contaminants were provided by the manufacturer and are QUA archived.

Housing - Granulated textured wood was used as bedding material for the cages. The cages were changed and cleaned twice a week. Periodic analysis of the bedding material for contaminants based on EPA/USA is conducted at least once a year by LUFA-ITL (limitation for contaminants in the bedding material: see Appendix 2. During the 14-day observation period the animals were kept by sex in groups of 2-3 animals in MAKROLON cages (type III) at a room temperature of 22 degrees C +/-3 degreesC (maximum range) and a relative humidity of 55%+/- (maximum range). Deviations from the maximum range caused for example dfuring cleaning procedures are dealt with in SPOPs. The rooms were lit (150 lux at approx. 1.5 m room height) and darkened for periods of 12 hours each.

Drinking water - Drinking water in bottles was offered ad libitum. Drinking waater is examined according to the "Deutsche Trinkwasserverordnung 2001' [German Regulations on drinking water 2001] by the Hamburger Wasserwerke, D20539 Hamburg, at least four times a year (limitation for contaminants in the drinking water: see Appendix 2). In addition, drinking water samples taken at LPT are analysed by
LUFA-ITL once a year for means of bacteriological investigations according to the German "Deutsche Trinkwasserverordnung 2001, Anlage 1' [German Regulations on drinking water 2001, Addendum 1].




























Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The study was carried out using a dynamic inhalation chamber (air changes/h (>/= 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (volume 40L) which holds a maximum of 20 animals in pyrex tubesat the edge of the chamber in a radial position. The dust of the test item was generated with a rotating brush dust generator. The generator was fed with compressed air (0.5 bar) from a compressor (air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-line disposable gas-filter). At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the spray-jet in order to produce a homogeneous distribution and a positive pressure in the exposure chamber. A manometer and an air-flow meter was used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary. The oxygencontent in the inhalation chamber was 21%. It was determined at the beginning and at the end of the exposure with a DRAGER Oxygen-analysis test set (DRAGER Tube Oxygen 67 28 081). The whole exposure system was mounted in an inhalation facility to protect the laboratory staff from possiblehazards.
Concentration (mg/L air): 5.05
Air flow entrance (L/h): 900
Air flow exit (L/h): 800
Air changes (changes per hour): 22.5
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Drager Tube Oxygen 67 28 081, Minisart SM 17598 0.45 UM (sample filter), Vacuubrand, MZ 2C6
Duration of exposure:
ca. 4 h
Concentrations:
5.05 mg/L air - actual concentration; nominal concentration - 848.9 mg/L air; 5.834 um mass median aerodynamic diameter; 1.061 mg/L air respirable amount particle size
No. of animals per sex per dose:
1 group of 5 males and 5 females
Control animals:
no
Details on study design:
After completion of exposure, the animals were observed for a period of 14 days. During and following exposure, observations were made and recorded systematically; individual records were maintained for each animal. A careful clinical examination was made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals, Cageside observation included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well assomatomotor activity and behaviour pattern. Particular attention was directed to observation of tremor, convulsions, salivation, diahhoea, lethargy, sleep and coma. Individual weights were determined before the exposure and weekly after exposure. Changes in weight were calculated and recordedwhen survival exceeds one day. At the end of the test, the surviving animals were weighed and sacrificed. Necropsy of animals was carried out and allgross pathological changes were recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.05 mg/L air
Exp. duration:
4 h
Mortality:
No mortality occurred
Clinical signs:
No clinical signs of toxicity
Body weight:
No inhibition of body weight gain
Gross pathology:
No abnormalities were detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information requires no classification Criteria used for interpretation of results: EU
Conclusions:
Under the present test conditions, the LC50-value for CD rats following inhalation of a dust of Litharge (Lead oxide) for 4 hours can be expected above an actual concentration of 5.05 mg/L air. According to the EC-Commission directive of September 1st, 1993 on the approximation of the laws, regulations and administrative provision relating to the classification packaging and labelling of dangerous substances (67/548/EC and its subsequent amendments) and the results obtained under the present test conditions, Litharge (Lead Oxide) requires no classification.
Executive summary:

The aim of the present experiment was to obtain information on the acute toxicity following single 4 -hour inhalation exposure of rats to Litharge (Lead Oxide) in an acute toxicity study designed as a test limit. Rats were exposed to a dust of Litharge (Lead oxide) at an actual concentration of 5.05 +/-0.010mg Litharge/L air for 4 hours by inhalation using a dynamic nose-only exposure chamber. In the inhalation chamber, close to the animals' noses, the particles had a mass median aerodynamic (MMAD) of 5.834UM as determined with a cascade impactor. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 4.814. The geometric mean diameter of the supplied test item was 11.430 um as determined with a Malvern Mastersizer. Under the present test conditions, a 4-hour exposure to a dust of Litharge (lead oxide at a concentration of 5.05 +/-0.10 mg Litharge/L air revealed no clinical signs of toxicity. No mortality occurred. No abnormalities were detected at necropsy. All animals gained the expected weight throughout the study period. The LC50 can be expected above an actual concentration of 5.05 mg Litharge/L air for 4 hours at 14 days. According to the EC-Commission directive 67/548/ECC and its subsequent amendments on the approximation of the laws, regulations, and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions. Litharge (Lead oxide) requires no classification.

These results can be assigned to lead silicate since a read across based on a grouping of substances (Pb substances) is applied.