Aluminium orthophosphate

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 13 April 2010 and 05 May 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: 15th Spetember 2009, Date of signature: 26th November 2009

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium orthophosphate

EC Number:

232-056-9

EC Name:

Aluminium orthophosphate

Cas Number:

7784-30-7

Molecular formula:

Al.H3O4P

IUPAC Name:

[phosphato(3-)-kappa~3~O,O',O'']aluminum

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Sponsor's identification: Aluminium orthophosphate
Description: white powder
Batch number: A88770A
Date received: 28 August 2009
Expiry date: 05 June 2010
Storage conditions: room temperature in the dark

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: 8-12 weeks
- Weight at study initiation: 166-188 g. 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): ad libitum (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: 13 April 2010 To: 05 May 2010

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

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 at a dose level of 2000 mg/kg /concentration of 200 mg/mL
- Amount of vehicle (if gavage): Not stated
- Justification for choice of vehicle: Not stated
- Lot/batch no. (if required): Not stated
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: Not applicable

CLASS METHOD (if applicable)
Not 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.

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: Clinical observations were made ½, 1, 2, and 4 hours after dosing and subsequently once 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
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

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:

There were no deaths in the 5 animals tested.

Clinical signs:

other: Individual clinical observations and mortality data are given in Table 1. No signs of systemic toxicity were noted.

Gross pathology:

Individual necropsy findings are given in Table 3.
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1. Individual clinical observations and mortality data.

 

 

Dose level mg/kg	Animal number and sex	Effects noted after dosing (hours)				Effects noted during periods after doing (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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

 

 

Table 2. Individual bodyweight and bodyweight changes

 

Dose level mg/kg	Animal number and sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
2000	1-0 Female	166	170	183	3	13
	2-0 Female	188	204	216	16	12
	2-1 Female	175	193	203	18	10
	2-2 Female	171	185	193	14	8
	2-3 Female	161	176	189	15	13

 

 

 

Table 3. 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	Killed day 14	No abnormalities detected

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 (Globally Harmonised Classification System: Unclassified).
This study is considered to be reliable and acceptable for use as a key study in accordance with Regulation (EC) No. 1907/2006 (REACH) and for the purposes of classification and labelling in accordance with 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” (adopted 17 December 2001)

 Method B1 bis 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.

There were no deaths.

Clinical Observations.

There were no signs of systemic toxicity.

Bodyweight.

All animals showed expected gains in bodyweight.

Necropsy.

No abnormalities were noted at necropsy.

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 (Globally Harmonised Classification System Unclassified).