Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 January 2010 - 08 February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD guideline 403 and under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Remarks:
Statement of Compliance
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): Phosphorous slag
- Physical state: powder
- Analytical purity: confidential
- Lot/batch No.: not indicated
- Expiration date of the lot/batch: confidential
- Stability under test conditions: stable
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
other: Crl:WI(Han) (outbred, SPF-Quality)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 11 weeks old
- Weight at study initiation: mean males: 329 gram; mean females: 218 gram. Body weight variation did not exceed +/- 20% of the sex mean.
- Housing: Animals were housed in a controlled environment. Group housing of 5 animals per sex per cage in labelled Macrolon cages. During exposure in a flow past nose-only inhalation chamber.
- Diet: pelleted rodent diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 - 22.0
- Humidity (%): 31 - 52
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a flow past nose-only inhalation chamber.
- Method of holding animals in test chamber: the animals were placed in restraining tubes, connected to the exposure chamber.
- Source and rate of air: the chamber consisted of 3 animal sections with 8 animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the test animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
- System of generating particulates/aerosols: administering the test substance to a stream of pressurized air (mean air flow 18.7 L/min.) using a combination of a spiral feeder and air mover generated an aerosol. The aerosol was passed through a cyclone, allowing larger particles to settle, before it entered the exposure chamber.
- Method of particle size determination: The particle size distribution was characterized twice during the exposure period. The samples were drawn (2 L/min) from the test atmosphere of the exposure chamber, and collected. Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.
- Temperature, humidity, pressure in air chamber: temperature (°C) during exposure: 17.9 - 18.6, humidity (%) during exposure: 28.9 - 30.8, mean air flow 18.7 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration was calculated by dividing the amount of test substance used by the volume of pressurized air (average air flow X exposure time) entering the exposure chamber used for exposure of the animals. The actual concentration was determined 8 times during the exposure period. Samples were drawn from the test atmosphere of the exposure chamber. The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter. Subsequently the mean concentration and standard deviation were calculated.
- Samples taken from breathing zone: no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The particle size distribution was characterized twice during the exposure period. The samples were drawn (2 L/min) from the test atmosphere of the exposure chamber, and collected. Amounts of test substance collected were measured gravimetrically.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD, the σ 84% were read from the graph. The GSD was calculated as σ 84%/ MMAD. The MMAD is the particle size where 50% of the particle mass is borne by particles smaller than the MMAD, the σ 84, is the particle size where 84% of the particle mass is borne by particles smaller than the σ 84%. The MMAD and GSD were determined twice. The MMAD was 2.7 um and 2.6 um respectively and the GSD was 1.9 and 1.9. respectively.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
the actual concentration was measured eight times during the exposure period
Duration of exposure:
ca. 4 h
Concentrations:
The mean actual concentration was 5.5 ± 0.2 mg/L (The nominal concentration was 85.4 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 6)%.
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/ViabiIity: twice daily. Clinical signs: 4 times during exposure for mortality, behavioral signs of distress, and effects on respiration. Twice (at 1 and at 3 hours after exposure) on the day of dosing (day 1) and once daily thereafter, until day 15. Body weights: Days 1 (pre-treatment), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.
Statistics:
No statistical analysis was performed (the method used was not intended to allow the calculation of a precise LC50 value).

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air
Exp. duration:
4 h
Remarks on result:
other: No mortality occured
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 85.4 mg/L air (nominal)
Exp. duration:
4 h
Remarks on result:
other: No mortality occured
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 5.5 mg/L air
Exp. duration:
4 h
Remarks on result:
other: No mortality occured
Mortality:
No mortality occured.
Clinical signs:
other: During exposure no clinical signs were noted, and after exposure on Day 1, lethargy, hunched posture and piloerection were noted in all animals. No clinical signs were seen after Day 1.
Body weight:
Body weight loss was noted in all animals during the first week post-exposure and all animals regained weight during the second week.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalatory LC50, 4h value of Phosphorous slag in Wistar rats was established to exceed 5 mg/L. As no deaths occurred the tested concentration can be considered as LC0. Based on these results Phosphorous slag does not have to be classified and has no obligatory labeling requirement for acute inhalation toxicity according to the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.
Executive summary:

An assessment of acute inhalatory toxicity with Phosphorous slag in the rat was performed. The study was carried out based on the OECD Guideline No.403, September 2009. Phosphorous slag was administered as an aerosol by inhalation for 4 hours to one group of 5 male and 5 female Wistar rats. Animals were subjected to daily observations and weekly determination of body weight. After an observation period of 14 days, the animals were sacrificed and macroscopic examination was performed. The mean actual concentration was 5.5 ± 0.2 mg/L. The nominal concentration was 85.4 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 6%. The mean mass aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined twice. The MMAD was 2.7 um and 2.6 um respectively and the GSD was 1.9 and 1.9. respectively.

No mortality occurred. During exposure, no clinical signs were noted and after exposure on Day 1, lethargy, hunched posture and piloerection were noted in all animals. No clinical signs were seen after Day 1. Body weight loss was noted in all animals during the first week post-exposure and all animals regained weight during the second week. No abnormalities were found at macroscopic post mortem examination of the animals. The inhalatory LC50,4hvalue of Phosphorous slag in Wistar rats was established to exceed 5 mg/L.

As no deaths occurred the tested concentration can be considered as LC0. Based on these results Phosphorous slag does not have to be classified and has no obligatory labeling requirement for acute inhalation toxicity according to the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.