Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21st May 2010 - 10th August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Values for relative humidity above the range occasionally occurred, usually following room cleaning, and were considered not to have any influence on the study.
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
Values for relative humidity above the range occasionally occurred, usually following room cleaning, and were considered not to have any influence on the study.
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of Inspection: 5th to 9th and 26th to 30th November 2007 Date of signature: 30th April 2008
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Aluminium tris(dihydrogen phosphate)
EC Number:
236-875-2
EC Name:
Aluminium tris(dihydrogen phosphate)
Cas Number:
13530-50-2
Molecular formula:
H6AlO12P3
IUPAC Name:
aluminium(3+) tridihydrogen phosphate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / Netherlands
- Age at study initiation: Males: 9 weeks, Females: 9 weeks
- Weight at study initiation: Males: 273.8 to 304.9 g, Females: 175.4 to 187.2 g
- Fasting period before study: Not applicable
- Housing: Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey, UK).
- Diet (e.g. ad libitum): Animals had ad libitum access to a pelleted standard Harlan Teklad 2914C rat maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) batch no. 82/09 except during the period when the animals were restrained in exposure tubes. Results of the analyses for contaminants and their limits of acceptability are archived at Harlan Laboratories Ltd.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum in water bottles, except during the period when they were restrained in exposure tubes. Results of representative analyses for contaminants are archived at Harlan Laboratories Ltd.
- Acclimation period: For ten days under laboratory conditions, after clinical health examination. Only animals without any visible signs of illness were used for the study. A further observation of clinical signs was performed on the day of exposure, before exposure start.


ENVIRONMENTAL CONDITIONS
Optimal Hygienic Conditions (OHC) inside a barrier system. Air-conditioned with 10 - 15 air changes per hour, continuously monitored environment with a temperature range of 22 ± 3 °C, a relative humidity range of 30 - 70% and a 12 hour fluorescent light / 12 hour dark cycle. Values for relative humidity above the range occasionally occurred, usually following room cleaning, and were considered not to have any influence on the study. These data are not reported but retained at Harlan Laboratories Ltd. A radio program was played during most of the light period.

IN-LIFE DATES: From: Day 1 To: Day 14

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Remarks:
flow-past
Vehicle:
clean air
Mass median aerodynamic diameter (MMAD):
2.56 µm
Geometric standard deviation (GSD):
2.38
Remark on MMAD/GSD:
Mean Mass Median Aerodynamic Diameter (µm) 2.56, 2.79 and 2.72
Inhalable Fraction (% <4 µm) 69.6%, 65.8% and 67.1%
Geometric Standard Deviation 2.38, 2.43 and 2.38
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: A CR3020 rotating brush aerosol generator connected to a micronizing jet mill. The aerosol generated was then discharged into the flow-past, nose-only exposure chamber through a 63Ni charge neutralizer.
- Exposure chamber volume: Not applicable (nose-only, flow-past inhalation exposure chamber)
- Method of holding animals in test chamber: The animals were confined separately in restraint tubes which were positioned radially around the flow-past, nose-only exposure chamber. Only the nose of each animal was exposed to the test atmosphere.
- Source of air: Compressed air was supplied by means of an oil free compressor and passed respiratory quality filters before it was introduced into the exposure system.
- Method of conditioning air: Respiratory quality filters
- System of generating particulates/aerosols: A dust aerosol was generated from the test item using a CR3020 rotating brush aerosol generator connected to a micronizing jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutralizer.
- Method of particle size determination: Mercer Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.).
- Treatment of exhaust air: Filtered
- Temperature, humidity, pressure in air chamber: The oxygen concentration, temperature and relative humidity of the test atmosphere were measured continuously during the exposure on test aerosol samples taken at a representative exposure port using a calibrated device. The results were recorded manually and are reported at 30 minute intervals from the start of exposure.

TEST ATMOSPHERE

- Brief description of analytical method used: Gravimetric determinations of aerosol concentration were performed four times during exposure. The samples were collected on a Millipore®durapore filter, Type HVLP loaded in a 47 mm inline stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.

- Samples taken from breathing zone: Yes

VEHICLE
No vehicle used.
Analytical verification of test atmosphere concentrations:
no
Remarks:
Gravimetric only
Duration of exposure:
4 h
Concentrations:
Mean Achieved (mg/L) 5.1
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:
All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to treatment on the day of exposure and on Days 2, 4, 8 and 15 or at death.

- Necropsy of survivors performed:
yes

- Other examinations performed:
None
Statistics:
No statistical analysis was performed as only one group was allocated to the study.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: CL not given
Mortality:
All animals survived the scheduled observation period.
Clinical signs:
other: Hunched posture, salivation, ruffled fur, labored breathing and breathing noises were noted in all animals after the end of exposure. Only ruffled fur, labored breathing and breathing noises were recorded on test day 2 and persisted up to test day 10. In
Body weight:
From test day 1 to test day 2, slight to moderate body weight loss was noted in all animals. From test day 2 to test day 4, reduced body weight gain was noted in four males and two females. Thereafter normal body weight development was recorded in all animals.
Gross pathology:
There were no macroscopic findings.
Other findings:
Not applicable.

Any other information on results incl. tables

The nominal aerosol concentration was 10.6 mg/L air.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 of MONOBASIC ALUMINIUM PHOSPHATE (FFB 716) obtained in this study was estimated to be greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration). There was no indication of relevant sex-related differences in toxicity of the test item.

This study is conducted according to an appropriate guideline and under the conditions of GLP, the study is therefore considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint.
Executive summary:

A group of five male and five female albino rats [RccHanTM:WIST(SPF)] was exposed by nose-only, flow-past inhalation for four hours to the test item atagravimetricallydetermined mean concentration of 5.1 mg/L air.All animals were observed for clinical signs and mortality during the inhalation exposure and the subsequent 14-dayobservation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy. On test day 15 all animals were sacrificed and necropsied.

The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats.

 

All animals survived the scheduled observation period.

 

Principal clinical signs consisted of hunched posture, ruffled fur, labored breathing, breathing noises and salivation in all animals after exposure. No symptoms were recorded during the observation period from test day 11 onwards.

 

From test day 1 to test day 2, transient body weight loss was noted in all animals. From test day 2 to test day 4 reduced body weight gain was recorded in most males and some females. Normal body weight development was observed thereafter.

 

No treatment-related macroscopic findings were recorded.

 

In conclusion, the LC50of MONOBASIC ALUMINIUM PHOSPHATE (FFB 716)obtained in this study was estimated to be greater than 5.1 mg/L air(gravimetrically determined mean aerosol concentration).There was no indication of relevant sex-related differences in toxicity of the test item.