Pentapotassium triphosphate

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 14 October 2009 and 04 November 2009.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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 GLP inspection: 06/04/2010 Date of Signature on GLP certificate: 26/11/2009

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentapotassium triphosphate

EC Number:

237-574-9

EC Name:

Pentapotassium triphosphate

Cas Number:

13845-36-8

Molecular formula:

H5O10P3.5K

IUPAC Name:

pentapotassium triphosphate

Details on test material:

Sponsor's identification : Pentapotassium triphosphate
Description : white granular solid
Batch number : 8-00247-56
Date received : 12 August 2009
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:

Animals and Animal Husbandry
Female Wistar (HsdRccHan(R)TM:WIST(R)TM) strain rats were supplied by Harlan Laboratories UK Limited, Bicester, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

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 to give a dose level of 2000mg/kg bodyweight.

- Amount of vehicle (if gavage):
Not stated

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

- Lot/batch no. (if required):
Not stated

- Purity:
Not stated


MAXIMUM DOSE VOLUME APPLIED:
10ml/kg


DOSAGE PREPARATION (if unusual):
Not applicable

CLASS METHOD (if 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 monitoredduring 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:

Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
Dose Level (mg/kg) 2000
Concentration (mg/ml) 200
Dose Volume (ml/kg) 10
Number of Rats 1 Female


In the absence of mortality at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose Level (mg/kg) 2000
Concentration (mg/ml) 200
Dose Volume (ml/kg) 10
Number of Rats 4 Female

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Clinical observations were made ½, 1, 2, and 4 hours after dosing and subsequently once daily for up to 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 or at death.

At the end of the observation period the surviving 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.

Mortality:

One animal was found dead one day after dosing.

Clinical signs:

other: Hunched posture was noted in all animals. Additional signs of systemic toxicity noted were ataxia and occasional body tremors. Surviving animals appeared normal one or two days after dosing.

Gross pathology:

Individual necropsy findings are given in Table 3.
Abnormalities noted at necropsy of the animal that died during the study were abnormally red lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

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 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	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	H	HA	H	HATo	H	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	HA	HA	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	H	HA	H	HATo	X
	2-3 Female	HA	HA	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0= No signs of systemic toxicity

H = Hunched posture

A = Ataxia

To = Occasional body tremors

X = Animal dead

Table 2              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	178	183	194		5	11
	2-0 Female	183	186	192		3	6
	2-1 Female	156	162	173		6	11
	2-2 Female	187	-	-	177	-	-
	2-3 Female	183	193	201		10	8

-= Animal dead

 

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	Found dead Day 1	Lugs: abnormally red Liver: dark Kidneys: dark
	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 (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). Pentapotassium triphosphate 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” (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. 

One animal was found dead one day after dosing.

Clinical Observations. 

Hunched posture was noted in all animals. Additional signs of systemic toxicity noted were ataxia and occasional body tremors. Surviving animals appeared normal one or two days after dosing.

Bodyweight. 

Surviving animals showed expected gains in bodyweight.

Necropsy. 

Abnormalities noted at necropsy of the animal that died during the study were abnormally red lungs, dark liver and dark kidneys. 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).