Polyphosphoric acids, ammonium salts

Endpoint summary

Description of key information

Key studies are available for acute oral and acute inhalation toxicity. These studies are performed under the conditions of GLP and to an appropriate OECD guideline. As such, these studies are considered to be adequate and reliable for use as key studies for the purpose of REACH Registration and classification and labelling in accordance with EU CLP. It is not considered necessary to provide acute dermal toxicity data.

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:

From 08 January 2015 to 11 February 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conclusive, performed to a valid guideline (OECD TG 420, adopted 17 December 2001) and was conducted under GLP conditions. No deviations from the test methods were noted.

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 GLP Inspection: 12 to 14 March 2014 Date of Signature on Certificate: 12 May 2014

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 Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 145-168g
- Fasting period before study: Overnight
- Housing: In groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK provided ad libitum
- Water (e.g. ad libitum): Mains drinking water provided ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): At least fifteen
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: The test item did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual):
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The available information on the toxicity of the test item was used to select 2000 mg/kg as the starting dose

Doses:

300 mg/kg, 2000 mg/kg

No. of animals per sex per dose:

Five animals per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes

Preliminary study:

Individual clinical observations and mortality data are given in Table 1. One animal was killed for humane reasons, 30 minutes after dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. One other animal was found dead 2 days after dosing. increased respiratory rate, labored respiration, prostration and tiptoe gait.
Surviving animals appeared normal 1 or 2 days after dosing. Individual necropsy findings are given in Table 3.
Abnormalities noted at necropsy of the animals that died or was humanely killed during the study were dark liver or patchy pallor of the liver, dark kidneys, gaseous stomach and hemorrhagic non-glandular epithelium of the stomach and/or hemorrhagic gastric mucosa.
No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Individual clinical observations and mortality data are given in Table 4. There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

Individual necropsy findings are given in Table 6.
No abnormalities were noted at necropsy.

Table 1:Individual Clinical Observations and Mortality Data - 2000 mg/kg

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	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	RlRdPrX*
	2-1 Female	HLa	HLPWt	HWt	HPRl	HWt	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	HA	HA	HA	HP	HWt	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	HA	HAWt	HWt	HPWt	HPPtRlRi	X

0 = No signs of systemic toxicity H = Hunched posture A = Ataxia L = Lethargy Pt = Ptosis P = Pilo-erection

Ri = Increased respiratory rate Rl = Labored respiration Pr = Prostration Wt = Tiptoe gait X = Animal dead

X* = One animal was killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence 

Table 2:Individual Body Weights and Body Weight Changes - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight (g) at Death	Body Weight Gain (g) During Week
		0	7	14		1	2
2000	1-0 Female	160	189	195	-	29	6
	2-0 Female	165	-	-	162	-	-
	2-1 Female	168	184	207		16	23
	2-2 Female	161	180	196		19	16
	2-3 Female	153	-	-	137	-	-

- = Animal dead 

Table 3:Individual Necropsy Findings - 2000 mg/kg

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	Humanely killed Day 0	Liver: patchy pallor Kidneys: dark Stomach: gaseous Gastric mucosa: hemorrhagic
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	2-3 Female	Found dead Day 2	Liver: dark Kidneys: dark Stomach: gaseous Gastric mucosa: hemorrhagic Non-glandular epithelium of the stomach: hemorrhagic

 

Table 4:Individual Clinical Observations and Mortality Data - 300 mg/kg

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
300	3-0 Female	0	0	0	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 Female	0	0	0	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-1 Female	0	0	0	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 Female	0	0	0	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 Female	0	0	0	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 L = Lethargy Pt = Ptosis P = Pilo-erection

Ri = Increased respiratory rate Rl = Labored respiration Pr = Prostration Wt = Tiptoe gait X = Animal dead

X* = One animal was killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence 

 

Table 5:Individual Body Weights and Body Weight Changes - 300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight Gain (g) During Week
		0	7	14	1	2
300	3-0 Female	167	182	193	15	11
	4-0 Female	187	205	212	18	7
	4-1 Female	189	211	222	22	11
	4-2 Female	181	199	204	18	5
	4-3 Female	190	211	221	21	10

- = Animal dead 

Table 6:Individual Necropsy Findings - 300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	3-0 Female	Killed Day 14	No abnormalities detected
	4-0 Female	Killed Day 14	No abnormalities detected
	4-1 Female	Killed Day 14	No abnormalities detected
	4-2 Female	Killed Day 14	No abnormalities detected
	4-3 Female	Killed Day 14	No abnormalities detected

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System - Category 4).

The test item was also classified as Category 4 according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures. It is reasonable to assume that the Signal Word “Warning” and the Hazard Statement “H302: Harmful if swallowed” are therefore required.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

Following a sighting test at a dose level of 2000 mg/kg, a group of four fasted animals was given a single oral dose of test item at the same dose level. Based on the results from this dose level an additional animal was treated with the test item at a dose level of 300 mg/kg body weight. Based on the results from this animal, a further group of four fasted animals was given a single oral dose of test item at a dose level of 300 mg/kg body weight.

The test item was administered orally as a suspension in arachis oil BP. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. One animal treated at a dose level of 2000 mg/kg was killed for humane reasons, 30 minutes after dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. One other animal treated at a dose level of 2000 mg/kg was found dead 2 days after dosing. There were no deaths at a dose level of 300 mg/kg.

Clinical Observations. Signs of systemic toxicity noted at a dose level of 2000 mg/kg were hunched posture, ataxia, lethargy, pilo-erection, ptosis, increased respiratory rate, labored respiration, prostration and tiptoe gait. Surviving animals treated at a dose level of 2000 mg/kg appeared normal 1 or 2 days after dosing. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Abnormalities noted at necropsy of the animals that died or was humanely killed during the study were dark liver or patchy pallor of the liver, dark kidneys, gaseous stomach and hemorrhagic non-glandular epithelium of the stomach and/or hemorrhagic gastric mucosa. 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 item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System  Category 4). The test item was also classified as Category 4 according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures. It is reasonable to assume that the Signal Word “Warning” and the Hazard Statement “H302: Harmful if swallowed” are therefore required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

One study is available to assess the acute oral toxicity of ammonium polyphosphate. The key study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint. In addition, the data is considered to be adequate and reliable for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).

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:

From 29 October 2014 to 09 December 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance with an accepted guideline (OECD TG 436) and under the conditions of GLP. No deficiencies are noted and the results are considered to be relaible.

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method B.52 (Acute Inhalation Toxicity - Acute Toxic Class Method, 2014)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Inspection: 12 to 14 March 2014 Date of Signature on Certificate: 12 May 2014

Test type:

acute toxic class 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 UK Ltd., Oxon, UK
- Age at study initiation: Eight to twelve weeks
- Weight at study initiation: 200-350 g
- Fasting period before study: None
- Housing: Solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., Cheshire , UK) and provided with environmental enrichment items: wooden chew blocks and cardboard "fun tunnels" (DatesandLtd., Cheshire)
- Diet (e.g. ad libitum): Harlan 2014C Rodent Diet, Harlan Laboratories, UK Ltd., Oxon, UK provided ad libitum
- Water (e.g. ad libitum): Mains drinking water provided ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): At least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light (06:00 to 18:00)

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK) was located at the top of exposure chamber. The nebuliser was connected to a plastic syringe attached to an infusion pump, which provided a continuous supply of test item under pressure, and to a metered compressed air supply.
- Exposure chamber volume: Approximately 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate resin restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring.
- Source and rate of air: Compressed air was supplied by means of an oil free compressor; the chamber flow rate was maintained at 60 L/min providing 120 air changes per hour
- Method of conditioning air: Passed through a water trap and respiratory quality filters
- System of generating particulates/aerosols: Nebuliser
- Method of particle size determination:
The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period during a Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK). This device consisted of six impactor stages (8.4, 7.3, 3.6, 1.3, 0.94, and 0.43 µm cut points) with stainless steel collection substrates and a backup glass fibre filter, housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by difference. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 8.4, 7.3, 3.6, 1.3, 0.94 and 0.43 µm was calculated.
- Treatment of exhaust air: The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: The tempreature and relative humidity inside the exposure chamber was measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd., Beds., UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.
- Oxgen concentration in air chamber: Oxygen levels were measured by an electronic oxygen analyser (Servomex (UK) Ltd, Crowborough, East Sussex) located in a port in the animals breathing zone during the four-hour exposure period. The test atmosphere was generated to contain at least 19% oxygen.

TEST ATMOSPHERE
- Brief description of analytical method used: During the characterisation phase of the study the test atmosphere was sampled twice and filter samples were then submitted for chemical analysis to determine if the original test item was similar to the composition of the airborne test item. A standard and samples were analysed spectrophotometrically using the following conditions:

Spectrophotometer: Camspec M550
Wavelength: 190-700 mm
Cell path length: 1 cm
Reference medium: water

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Target concentrated of 5.0 mg/L. Mean achieved atmosphere concentration: 4.85 mg/L - 97% of target.

No. of animals per sex per dose:

3 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for clinical signs were made at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exppsure and subsequently once daily for up to fourteen days.
Individual body weights were recorded on arrival, prior to treatment on the day of exposure and on Days 1,3, 7 and 14 or at death.
- Necropsy of survivors performed: Yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.85 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0/3 males died and 1/3 females died.

Clinical signs:

other: Individual clinical observations are given in Table 1 and 2. Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both duri

Body weight:

Individual body weights, together with body weight changes, are given in Table 3.

All animals exhibited body weight losses on the first day post-exposure. Two males and two female animals exhibited further body weight losses from Days 1 to 3 post-exposure. Body weight gains were noted in all surviving aimals during the remainder of the recovery period.

Gross pathology:

Individual necropsy findings are given in Table 4.

No macroscopic abnormalities were detected amongst animals that survived until the end of the recovery period at necropsy.

The following macroscopic abnormalities were detected at necropsy in the female animal that was humanely killed during the course of the study.

Liver - pale and accentuated lobular pattern
Stomach - gaseous distension
Small intestine - gaseous distension
Large intestine - gaseous distension

Key to clinical observations

Da = distended abdomen

Dh = dehydration

H = hunched posture

P = pilo-erection

Rd = decreased respiratory rate

Rg = gasping respiration

Ri = increased respiratory rate

Rl = labored respiration

Rn = noisy respiration

Wf = wet fur

X* = animal killed in extremis

0 = no abnormalities detected

Table 1: Individual clinical observations (day of exposure)

Mean achieved atmosphere concentration (mg/L)	Animal number and sex	Hours During Exposure			On removal from chamber	One hour post-exposure
		1	2	3
4.85	1 Male	Wf	Wf	Wf	Wf H P Ri	Wf H P Ri
	2 Male	Wf	Wf	Wf	Wf H P Ri	Wf H P Ri
	3 Male	Wf	Wf	Wf	Wf H P Ri	Wf H P Ri
	4 Female	Wf	Wf	Wf	Wf H P Ri	Wf H P Ri
	5 Female	Wf	Wf	Wf	Wf H P Ri Rn Rg	Wf H P Ri Rn Rg
	6 Female	Wf	Wf	Wf	Wf H P Ri	Wf H P Ri

Table 2: Individual clinical observations (recovery period)

Mean achieved atmosphere concentration (mg/L)	Animal number and sex	Days Post Exposure
		1	2	3	4	5	6	7	8-14
4.85	1 Male	H P Ri	H P Ri	H P Ri	H Ri	H Ri	H	0	0
	2 Male	H P Ri	H P Ri	H	H	H	H	0	0
	3 Male	H P Ri	H P Ri	H P Ri	H Ri	H Ri	H	0	0
	4 Female	H P Ri	H P Ri	H Ri	H Ri	H Ri	Ri	0	0
	5 Female	H P Rd Rl Rn Rg	H P Ri Rn	H P Rd Rl Rn Rg Da Dh X*
	6 Female	H P Ri	H P Ri	H Ri	H Ri	H Ri	Ri	0	0

Table 3 Individual Body Weights

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Body Weight (g) on Day:							Increment (g) During Days:
		-20	0	1	3	7	14	At Death	-20-0	0-1	1-3	3-7	7-14
0.54	1 Male	200	296	270	254	262	281		96	-26	-16	8	19
	2 Male	206	298	273	284	300	349		92	-25	11	16	49
	3 Male	204	299	267	254	270	307		95	-32	-13	16	37
	4 Female	208	219	202	201	208	222		11	-17	-1	7	14
	5 Female	206	238	212	187	-	-	187	32	-26	-25	-	-
	6 Female	207	247	217	220	241	244		40	-30	3	21	3

Table 4 Individual Necropsy Findings

Mean Achieved Atmosphere Concentration (mg/L)	Macroscopic Observations	Animal Number and Sex
		1 Male	2 Male	3 Male	4 Female	5* Female	6 Female
4.85	Liver: Pale           Accentuated                                                   lobular pattern					P P
	Stomach: Gaseous distension					P
	Small intestine: Gaseous distension					P
	Large intestine: Gaseous distension					P
		N	N	N	N		N

P = finding present

N = no abnormalities detected

* = Animal humanely killed during study

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

One death occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 4.85 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration ( 4 hr LC50) of polyphosphoric acids, ammonium salts (liquid) in the RccHan™: WIST strain rat, was greater than 4.85 mg/L. In accordance with Regulation (EC) No. 1272/2008 (EU CLP) ammonium polyphosphate is not considered to be classified as acutely toxic via the inhalation route.

The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

According to the criteria of classification of GHS (Globally Harmonised Classification System) the substance is classified in Acute Toxicity Inhalation Category 5 due to the mortality and clinical signs observed in one animal.

Executive summary:

A study was performed to assess the acute inhalation toxicity of the test item. The method used was designed to be compatible with that described in the OECD Guideline for Testing of Chemicals (2009) No. 436 "Acute Inhalation Toxicity - Acute Toxic Class Method" and Method B.52 Acute Inhalation Toxicity - Acute Toxic Class Method, 2014, of Commission Regulation (EC) No. 440/2008.

A group of six RccHan™: WIST strain rats (three males and three females) was exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

The mean achieved atmospheric concentration was as follows:

Atmosphere Concentration
Mean Achieved (mg/L)	Standard deviation	Nominal (mg/L)
4.85	0.48	42.9

The characteristics of the achieved atmosphere were as follows:

Mean Achieved Atmosphere Concentration (mg/L)	Mass Median Aerodynamic Diameter (µm)	Inhalable Fraction (% < 4µm)	Geometric Standard Deviation
4.85	2.48	72.7	2.22

The mortality data were summarised as follows:

Mean achieved atmosphere concentration (mg/L)	Deaths
	Male	Female	Total
4.85	0/3	1/3	1/6

Clinical observations

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. One animal also exhibited decreased respiratory rate, labored respiration, gasped respiration, noisy respiration, dehydration and a distended abdomen. Surviving animals recovered to appear normal on Day 7 post-exposure.

Body weight

All animals exhibited body weight losses on the first day post-exposure. Two males and two female animals exhibited further body weight losses from Days 1 to 3 post-exposure. Body weight gains were noted in all surviving animals during the remainder of the recovery period.

Necropsy

No macroscopic abnormalities were detected amongst animals that survived until the end of the recovery period at necropsy.

The following macroscopic abnormalities were detected at necropsy in the female animal that was humanely killed during the course of the study:

Liver - pale and accentuated lobular pattern;

Stomach - gaseous distension;

Small intestine - gaseous distension;

Large intestine - gaseous distension.

The 4 hr LC₅₀ was considered to be greater than 4.85 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 850 mg/m³ air

Quality of whole database:

One key study is available to assess the acute inhalation toxicity of ammonium polyphosphate. This study was performed on the liquid product as this is the form that is placed on the EU market. The key study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint. In addition, the data is considered to be adequate and reliable for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Data are provided on the acute oral toxicity of solid ammonium phosphate (anhydrous) and the acute inhalation toxicity of ammonium polyphosphate, liquid (hydrated form placed on the EU market). It was deemed appropriate to perform the acute inhalation study on the liquid form as inhalation of liquid droplets during spray applications was deemed to be a major route of exposure for the material as the solid form of the substance is not placed on the EU market.

Justification for selection of acute toxicity – oral endpoint
This study is conducted according to an appropriate guideline (OECD 423) and under the conditions of GLP.

Justification for selection of acute toxicity – inhalation endpoint
This study is conducted according to an appropriate guideline (OECD 436) and under the conditions of GLP.

Justification for selection of acute toxicity – dermal endpoint
No study available.

Justification for classification or non-classification

Acute oral toxicity:The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight. Therefore ammonium polyphosphate is classified as acute toxicity category 4 with the hazard statement 'H302: Harmful if swallowed'.

Acute inhalation toxicity:The acute inhalation median lethal concentration (4 hr LC50) of polyphosphoric acids, ammonium salts (liquid) in the RccHan™: WIST strain rat, was determined to be > 4.85 mg/L.Therefore in accordance with Regulation (EC) No. 1272/2008 (EU CLP)ammonium polyphosphate is not classified for acute inhalation toxicity. 

 

Acute dermal toxicity:There are no data to suggest that ammonium polyphosphate is classified for acute dermal toxicity and therefore no classification is proposed.