Iron orthophosphate

Endpoint summary

Description of key information

Oral: OECD 420, RL1, rat: LD50 > 2000 mg/kg bw
Inhalation: OECD 436, RL1, rat, dust: LC50 > 5.05 mg/L

Dermal: no study available

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:

Between 24 November 2011 and 20 December 2011

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)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., 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 bodyweight of the initially dosed animal.
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 (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., 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.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe.

Doses:

300 mg/kg
2000 mg/kg

No. of animals per sex per dose:

1 female at 300 mg/kg
1 female at 2000 mg/kg
4 females at 2000 mg/kg

Control animals:

no

Details on study design:

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 the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
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.
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.

Preliminary study:

Dose Level - 300 mg/kg
Individual clinical observations and mortality data are given in Table 1.

Mortality
There was no mortality.

Clinical Observations
No signs of systemic toxicity were noted during the observation period.

Bodyweight
Individual bodyweights and bodyweight changes are given in Table 2.
The animal showed expected gains in bodyweight over the observation period.

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose Level - 2000 mg/kg
Individual mortality data are given in Table 4.
There were no deaths.

Clinical signs:

other: Dose Level - 2000 mg/kg Individual clinical observations are given in Table 4. No signs of systemic toxicity were noted during the observation period.

Gross pathology:

Dose Level - 2000 mg/kg
Individual necropsy findings are given in Table 6.
No abnormalities were noted at necropsy.

Other findings:

None

Evaluation of Data

Data evaluations included the relationship, if any, between the animals' exposure to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. If possible the signs of evident toxicity were also identified. Evident toxicity is defined as the toxic effects which are of a severity such that administration at the next highest level could result in mortality.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD₅₀) of the test item was made.

Table 1              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	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=     No signs of systemic toxicity

Table 2              Individual Bodyweights and Bodyweight Changes - 300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	160	167	194	7	27

Table 3              Necropsy Findings - 300 mg/kg

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

Table 4              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	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=     No signs of systemic toxicity

Table 5              Individual Bodyweights and Bodyweight Changes - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	2-0 Female	158	171	190	13	19
	3-0 Female	160	182	193	22	11
	3-1 Female	168	190	207	22	17
	3-2 Female	161	183	208	22	25
	3-3 Female	168	189	209	21	20

 Table 6             Individual Necropsy Findings - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Killed Day 14	No abnormalities detected
	3-2 Female	Killed Day 14	No abnormalities detected
	3-3 Female	Killed Day 14	No abnormalities detected

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

The acute oral median lethal dose (LD50) of the test item 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 scientifically justified for use as a key study under Regulation (EC) No. 1907/2006 and the results are appropriate 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 item in the Wistar strain rat. The method was designed to be compatible with the following:

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

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

Method. Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item, 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 item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

10th October 2011 - 17 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 (UK) Ltd.

- Age at study initiation:
approximately eight to twelve weeks old

- Weight at study initiation:
200g to 350g.

- Fasting period before study:
Not applicable

- Housing:
The animals were housed in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks and cardboard “fun tunnels”

- Diet:
ad libitum

- Water:
ad libitum

- Acclimation period:
at least five days


ENVIRONMENTAL CONDITIONS

- Temperature:
19 - 25°C

- Humidity:
30 - 70 %

- Air changes (per hr):
at least fifteen changes per hour

- Photoperiod (hrs dark / hrs light):
twelve hours continuous light and twelve hours darkness


IN-LIFE DATES:
From: 26 October 2011 To: 17 November 2011

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.96 µm

Geometric standard deviation (GSD):

3.22

Remark on MMAD/GSD:

Inhalable Fraction (% <4 µm) 60.2

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) plus cylindrical exposure chamber

- Exposure chamber volume:
approximately 30 litres

- Method of holding animals in test chamber:
Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.

- Source and rate of air:
Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the SAG 410. 60 L/min providing 120 air changes per hour

- Method of conditioning air:
water trap and respiratory quality filters

- System of generating particulates:
SAG 410 Solid Aerosol Generator , a particle separator was introduced before the aerosol entered the exposure chamber in order to remove large particles and thereby increase the inhalable portion of the generated aerosol.

- Method of particle size determination:
Marple Personal Cascade Impactor .

- Treatment of exhaust air:
filtered

- Temperature, humidity, pressure in air chamber: temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animals’ breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.


TEST ATMOSPHERE
- Brief description of analytical method used:
glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump (Gravimetric).

- Samples taken from breathing zone:
yes


VEHICLE
- Composition of vehicle (if applicable):
Not applicable

- Concentration of test material in vehicle:
Not applicable

- Justification of choice of vehicle:
Not applicable

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

- Purity: Not applicable


TEST ATMOSPHERE (if not tabulated)

- Particle size distribution: tabulated
- MMAD (Mass median aerodynamic diameter: 9.93 µm

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Not applicable.

Analytical verification of test atmosphere concentrations:

no

Remarks:

Gravimetric only

Duration of exposure:

4 h

Concentrations:

Mean Achieved (mg/L) 5.05

No. of animals per sex per dose:

3

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 Individual bodyweights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs.

Statistics:

Data evaluations included the relationship, if any, between the animals’ exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, necropsy findings, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.05 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 5.05 mg/L for four hours
See Appendix 3 Mortality Data in the overall remarks section.

Clinical signs:

other: Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. See Appendix 4 Individual Clinical Observations(Day of Exposure) and Appendix 5  Individual Clinical Observations (Recovery Peri

Body weight:

All animals exhibited bodyweight losses or showed no bodyweight gain on the first day post-exposure. All animals exhibited reasonable bodyweight developments throughout the remainder of the recovery period. With the exception of one female animal which showed no bodyweight gain from Days 3 to 7 post-exposure. See Appendix 6.
Appendix 6 Individual Bodyweights in the overall remarks section.

Gross pathology:

No macroscopic abnormalities were detected amongst animals at necropsy.

Other findings:

Not applicable.

Exposure Chamber Concentration

The test atmosphere was sampled seventeen times during the exposure period and the actual concentration of the test item calculated. The mean values obtained were:

Atmosphere Concentration
Mean Achieved (mg/L)	Standard Deviation	Nominal (mg/L)
5.05	0.11	9.22

The chamber flow rate was maintained at 60 L/min providing 120 air changes per hour.The theoretical chamber equilibration time (T₉₉) was 3 minutes (Silver, 1946). However,Test atmospheres were generated for a total of 24 minutes prior to animal insertion to ensure test item concentration was being achieved.

Particle Size Distribution

The particle size analysis of the atmosphere drawn from the animals’ breathing zone, was as follows:

Mean Achieved Atmosphere Concentration (mg/L)	Mean Mass Median Aerodynamic Diameter (µm)	Inhalable Fraction (% <4 µm)	Geometric Standard Deviation
5.05	2.96	60.2	3.22

Mortality Data

The mortality data are given in Appendix 3 and are summarised as follows:

Mean Achieved Atmosphere Concentration (mg/L)	Deaths
	Male	Female	Total
5.05	0/3	0/3	0/6

Appendix1      Exposure Chamber Atmosphere Concentrations

Duration of Exposure (minutes)	Net Weight of Sample (mg)	Volume of Air Sampled (L)	Chamber Flow Rate (L/min)	Atmosphere Concentration (mg/L)
5	10.04	2	60	5.02
15	9.94	2	60	4.97
30	10.11	2	60	5.06
45	10.04	2	60	5.02
60	9.91	2	60	4.96
75	10.26	2	60	5.13
90	10.11	2	60	5.06
105	10.11	2	60	5.06
120	10.25	2	60	5.13
135	10.16	2	60	5.08
150	10.71	2	60	5.36
165	9.85	2	60	4.93
180	10.06	2	60	5.03
195	9.75	2	60	4.88
210	9.78	2	60	4.89
225	10.31	2	60	5.16
238	10.12	2	60	5.06

Mean achieved atmosphere concentration (mg/L) =5.05

Standard deviation =0.11

Nominal concentration:

Test item used (g)	146
Air Flow (L/min)	60
Total Generation Time (mins)	264
Nominal Concentration (mg/L)	9.22

[1]= Test atmospheres were generated for a total of 24 minutes prior to animal insertion to ensure test item concentration was being achieved.

Appendix2      Particle Size Distribution

Cascade Impactor Data

Impactor Stage Number	Cut Point (µm)	Amount Collected (mg) per Sample Number			Mean Amount Collected (mg)
		1	2	3
3	8.8	0.33	0.29	0.04	0.22
4	5.8	0.45	0.50	0.10	0.35
5	3.6	0.38	0.37	0.20	0.32
6	1.9	0.59	0.62	0.33	0.51
7	0.79	0.11	0.14	0.34	0.20
8	0.33	0.14	0.12	0.15	0.14
Back-up Filter	<0.33	0.04	0.06	0.20	0.10
Total Mean Amount of Test Item Collected					1.84

Calculation

Cut Point (µm)	Log10 Cut Point	Mean Cumulative Amount Less Than Cut Point
		(mg)	(%)	Probit
8.8	0.945	1.62	88.0	6.18
5.8	0.763	1.27	69.0	5.50
3.6	0.556	0.95	51.6	5.04
1.9	0.279	0.44	23.9	4.29
0.79	-0.102	0.24	13.0	3.88
0.33	-0.482	0.10	5.44	3.40

Results

Mean Mass Median Aerodynamic Diameter (MMAD) =2.96µm

Geometric Standard Deviation (GSD) =3.22

Predicted amount less than 4 µm =60.2%

Appendix 3        Mortality Data

Mean Achieved Atmosphere Concentration (mg/L)	Sex	Deaths During Exposure	Deaths Post Exposure (1 Hour)	Deaths During Day of Observation								Total Deaths
				1	2	3	4	5	6	7	8-14
5.05	Male	0	0	0	0	0	0	0	0	0	0	0/6
	Female	0	0	0	0	0	0	0	0	0	0

Appendix 4    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
5.05	1 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	2 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	3 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	4 Female	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	5 Female	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	6 Female	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri

Appendix 5    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
5.05	1 Male	H Ri	0	0	0	0	0	0	0
	2 Male	H Ri	0	0	0	0	0	0	0
	3 Male	H Ri	0	0	0	0	0	0	0
	4 Female	H Ri	Ri	Ri	Ri	0	0	0	0
	5 Female	H Ri	Ri	Ri	Ri	0	0	0	0
	6 Female	H Ri	Ri	Ri	Ri	0	0	0	0

Appendix 6    Individual Bodyweights.

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Bodyweight (g) on Day:						Increment (g) During Days:
		-8	0	1	3	7	14	-8-0	0-1	1-3	3-7	7-14
5.05	1 Male	215	257	250	260	276	299	42	-7	10	16	23
	2 Male	223	274	264	268	289	318	51	-10	4	21	29
	3 Male	215	278	278	287	303	333	63	0	9	16	30
	4 Female	191	202	198	199	199	205	11	-4	1	0	6
	5 Female	202	218	217	222	227	239	16	-1	5	5	12
	6 Female	199	212	208	213	217	224	13	-4	5	4	7

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 5.05 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of IP 27 Iron orthophosphate, in the RccHanTM : WIST strain rat, was greater than 5.05 mg/L (Globally Harmonised Classification System – Unclassified). This study is considered to be scientifically justified for use as a key study under Regulation (EC) No. 1907/2006 and the results are appropriate for the purposes of classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).

Executive summary:

Introduction.

A study was performed to assess the acute inhalation toxicity of the test item. The method used was compatible with that described in the OECD Guidelines for Testing of Chemicals (2009) No. 436 “Acute Inhalation Toxicity – Acute Toxic Class Method”.

Methods.

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

Results.The mean achieved atmosphere concentration was as follows:

Atmosphere Concentration
Mean Achieved (mg/L)	Standard Deviation	Nominal (mg/L)
5.05	0.11	9.22

The characteristics of the achieved atmosphere were as follows:

Mean Achieved Atmosphere Concentration (mg/L)	Mean Mass Median Aerodynamic Diameter (µm)	Inhalable Fraction (% <4 µm)	Geometric Standard Deviation
5.05	2.96	60.2	3.22

The mortality data were summarised as follows:

Mean Achieved Atmosphere Concentration (mg/L)	Deaths
	Male	Female	Total
5.05	0/6	0/6	0/6

Clinical Observations.

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. Animals recovered to appear normal from Days 2 to 5 post-exposure.

Bodyweight.

All animals exhibited bodyweight losses or showed no bodyweight gain on the first day post-exposure. All animals exhibited reasonable bodyweight developments throughout the remainder of the recovery period. With the exception of one female animal which showed no bodyweight gain from Days 3 to 7 post-exposure. 

Necropsy.

No macroscopic abnormalities were detected amongst animals at necropsy.

Conclusion.No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of5.05mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC₅₀) of IP 27 Iron orthophosphate, in the RccHan^TM: WIST strain rat, was greater than 5.05mg/L (Globally Harmonised Classification System – Unclassified).  

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

A reliable study according to OECD 420 and in compliance with GLP is available with iron orthophosphate (Harlan, 2012) in Wistar rats. Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further group of four fasted females was given a single oral dose of test item, as a suspension in distilled water, at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths and no signs of systemic toxicity was observed. All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy. Thus, the acute oral median lethal dose (LD50) of the test item in the female Wistar rats was estimated to be greater than 2000 mg/kg bw.

Inhalation:

A reliable study according to test guideline OECD 436 and in compliance with GLP is available with iron orthophosphate (Harlan, 2012) in rats. A group of six RccHanTM : WIST rats (three males and three females) was exposed to a dust 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 5.05 mg/L with a standard deviation of 0.11. The mean mass median aerodynamic diameter was reported as 2.96 µm with a geometric standard deviation of 3.22. The inhalabe fraction (< 4 µm) was 60.2%. No animal died during this study. Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. Animals recovered to appear normal from Days 2 to 5 post-exposure. All animals exhibited bodyweight losses or showed no bodyweight gain on the first day post-exposure. All animals exhibited reasonable bodyweight developments throughout the remainder of the recovery period. With the exception of one female animal which showed no bodyweight gain from Days 3 to 7 post-exposure. No macroscopic abnormalities were detected amongst animals at necropsy. It was therefore considered that the acute inhalation median lethal concentration (4 h LC50) of iron orthophosphate, in the RccHanTM : WIST rat, was greater than 5.05 mg/L.

Dermal:

Iron orthophosphate is an inorganic chemical with a molecular weight of >100 g/mol and is practically insoluble in water and lipids, therefore, systemic absorption via the dermal route is unlikely and as such inhalation and oral routes are considered to be a worst-case for systemic absorption. In addition, no signs of systemic toxicity were observed in in vivo skin irritation and skin sensitisation studies conducted on iron orthophosphate and therefore it can be reliably assumed that a full characterisation of the acute systemic toxicity profile of iron orthophosphate can be derived from the acute oral and inhalation studies and as such further in vivo testing would be unethical and could not be scientifically justified. Iron orthophosphate is not actue toxic by oral and inhalation route. Based on the above given information it can be concluded that iron orthophosphate will also not be acute toxic by dermal route.

Justification for classification or non-classification

The available data on acute oral, dermal and inhalation toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.