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Administrative data

Description of key information

Acute oral toxicity: A GLP study conducted according to OECD Guideline 401 concludes that the LD50 is greater than 2000mg/kg bw, (with 1/5 deaths at 2000mg/kg). According to Regulation (EC) No 1272/2008 (EU CLP) the test material will not be classified. This conclusion is supported by supporting data. 
Acute dermal toxicity: Testing was waived on the basis that further in vivo testing is considered to be scientifically unjustified (see discussion below).
Acute inhalation toxicity: A GLP study conducted according to OECD Guideline 403 is available to assess the acute inhalation toxicity of aluminium tris(dihydrogen phosphate). The acute inhalation median lethal concentration (LC50) was found to be greater than 5.1 mg/ L (with no animal deaths resulting from treatment). In accordance with Regulation EC (No.) 1272/2008 (EU CLP) aluminium tris(dihydrogen phosphate) will not be classified for acute inhalation toxicity.

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:
The study was performed between 25 May 2010 and 10 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: 15 September 2009 Date of Signature: 26 November 2009
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
Harlan Laboratories UK Limited, Bicester, Oxon, UK.

- Age at study initiation:
At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation:
The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

- Fasting period before study:
overnight fast immediately before dosing

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.

- Diet (e.g. ad libitum):
(2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed ad libitum throughout the study.

- Water (e.g. ad libitum):free access to mains drinking water

- Acclimation period:acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light):
lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From: Day 1 To: Day 14
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water to give a dose level of 2000mg/kg bodyweight.

- Amount of vehicle:
Not stated

- Justification for choice of vehicle:
Distilled water was the preferred vehicle of the test method.

- Lot/batch no.:
Not stated

- Purity:
Not stated


MAXIMUM DOSE VOLUME APPLIED:
10ml/kg


DOSAGE PREPARATION:
Not applicable

CLASS METHOD:
Bot applicable

- Rationale for the selection of the starting dose:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
Doses:
Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.
No. of animals per sex per dose:
1 female at 2000 mg/kg
4 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed:
Yes

- Other examinations performed:
Clinical signs, body weight.
Statistics:
Not available
Preliminary study:
A sighting test at a dose level of 2000 mg/kg was performed.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits not given in study report.
Mortality:
One animal was found dead ten minutes after dosing.
Clinical signs:
other: Hunched posture was noted in three animals during the day of dosing. No signs of systemic toxicity were noted in the initial treated animal.
Gross pathology:
White liquid present in the stomach was noted at necropsy of the animal that died during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Other findings:
- Organ weights:
Not recorded

- Histopathology:
Not recorded

- Potential target organs:
Not recorded

- Other observations:
None

Table1              Individual Clinical Observations and Mortality Data

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0

Female

0

0

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

0

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3

Female

X*

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


0=     No signs of systemic toxicity

H =      Hunched posture

X*=     Animal found dead ten minutes after dosing


Table2              Individual Bodyweights and Bodyweight Changes

Dose Level

mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight (g)
at Death

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

1-0 Female

189

205

214

 

16

9

2-0 Female

158

172

179

 

14

7

2-1 Female

161

178

183

 

17

5

2-2 Female

189

194

207

 

5

13

2-3 Female

167

-

-

162

-

-


-=       Animal dead

Table3              Individual Necropsy Findings

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

1-0 Female

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

2-3 Female

Found dead Day 0

Stomach: white liquid present

 


Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (not classified - EU CLP).
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation EC (No.) 1272/2008 (EU CLP). Aluminium tris(dihydrogen phosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted17 December 2001)

Method B1bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. One animal was found dead ten minutes after dosing.

Clinical Observations. Hunched posture was noted in three animals during the day of dosing.

Bodyweight. Surviving animals showed expected gains in bodyweight.

Necropsy. White liquid present in the stomach was noted at necropsy of the animal that died during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Conclusion. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Not classified - EU CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One key study exists, this study is conducted according to an acceptable guideline (OECD 420) and under the conditions of GLP. Therefore, the study is considered to be Klimisch 1. Supporting data are also submitted, these studies are not considered acceptable for classification and labelling however they do support the conclusions of the key study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
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
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
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.
Preliminary study:
Not applicable
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.

The nominal aerosol concentration was 10.6 mg/L air.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 100 mg/m³ air
Quality of whole database:
One key study exists, this study is conducted according to an acceptable guideline (OECD 403) and under the conditions of GLP. Therefore, the study is considered to be Klimisch 1.

Acute toxicity: via dermal route

Endpoint conclusion
Quality of whole database:
No data available

Additional information

No study is provided for the following reasons: According to Annex VIII, Section 8.5.3, Column 2 of Regulation No 1907/2006, testing by the dermal route is not appropriate when the physicochemical and toxicological properties suggest that the rate of absorption through the skin will not occur at a significant rate.

- The molecular weight of the substance is 318, this makes dermal absorption unfavourable*. It is therefore considered unlikely that aluminium tris(dihydrogen phosphate) [MALP] will become readily available for systemic absorption via the dermal route.

- Further to this, studies conducted to assess the potential for acute oral and inhalation toxicity concluded that MALP is not classified in accordance with Regulation (EC) No. 1272/2008 (EU CLP). As it is considered likely that absorption via the oral or inhalation routes will be greater than total systemic absorption via the dermal route, it has been concluded that MALP will also not be classified for acute dermal toxicity. Further in vivo testing is considered scientifically unjustified.

*According to the guidance on information requirements and chemical safety assessment; Chapter R.7c: Endpoint specific guidance.

Justification for classification or non-classification

Acute oral toxicity: Aluminium tris(dihydrogen phosphate) is not considered to be classified in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The key study is considered to be adequate and reliable for the purposes of classification and therefore further in vivo testing is not considered to be scientifically justified.

Acute inhalation toxicity: Aluminium tris(dihydrogen phosphate) is not considered to be classified for acute inhalation toxicity in accordance with Regulation (EC) No. 1272/2008 (EU CLP).The key study is considered to be adequate and reliable for the purposes of classification and therefore further in vivo testing is not considered to be scientifically justified.

Acute dermal toxicity: Aluminium tris(dihydrogen phosphate) is not considered to be classified for acute dermal toxicity in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Further in vivo testing is not considered to be scientifically justified.