Aluminium tris(dihydrogen phosphate)

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

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:

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

Administration / exposure

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

Results and discussion

Preliminary study:

A sighting test at a dose level of 2000 mg/kg was performed.

Effect levels

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

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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).