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Administrative data

Description of key information

LD50, Oral, Rats > 2000 mg/kg bodyweight.
LD50 (4 hours), Inhaled, Rats > 5.75 mg/L.

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:
11 May 2010 - 21 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to official EC and OECD test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Species:
rat
Strain:
other: Crl:CD "SD"
Sex:
female
Details on test animals and environmental conditions:
The animals were allocated without conscious bias to cages within the treatment groups.
They were housed in groups of three rats of the same sex, in solid bottomed polycarbonate
cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood
flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate
intervals.
Each animal was assigned an alpha-numeric code and identified uniquely within the study by
tail marking. Each cage label was colour-coded and was identified uniquely with the study
number, dose level and animal mark.
The animal room was kept at positive pressure with respect to the outside by its own supply
of filtered fresh air, which was passed to atmosphere and not re-circulated. The temperature
and relative humidity controls were set to maintain the range of 19 to 23°C and 40 to 70%
respectively. Any minor deviations from these ranges would not have had an adverse effect
on the animals and would not affect the integrity or validity of the study. Artificial lighting
was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per
24 hours.
Route of administration:
oral: gavage
Vehicle:
other: 1% (w/v) aqueous methylcellulose
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
The test substance was formulated at concentrations of 30 and 200 mg/mL in the vehicle and
administered at a volume of 10 mL/kg bodyweight.
The test substance formulations were prepared on the day of dosing.
The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1
Maintenance Diet), except for overnight prior to and approximately four hours after dosing.
This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
Potable water taken from the public supply was freely available via polycarbonate bottles
fitted with sipper tubes.
During the acclimatisation and study periods, each cage of animals was provided with a soft
white untreated chew block and a plastic shelter for environmental enrichment.
The absorption of the test substance was not determined.
Determination of the homogeneity, stability and purity of the test substance or test substance
formulations were not undertaken as part of this study.
Detailed records of test substance usage were maintained. The amount of test substance
necessary to prepare the formulations and the amount actually used were determined on each
occasion. The difference between these amounts was checked before the formulations were
dispensed.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths during the study.
Clinical signs:
Clinical signs of reaction to treatment comprised faeces abnormal colour (black) seen in all
females dosed at 300 mg/kg and three females (A7, A8 and A9) dosed at 2000 mg/kg. These
signs were first noted approximately thirty minutes or two hours after dosing, and had
resolved by Day 2.
Body weight:
A low bodyweight gain was recorded between Days 8 – 15 for two females (A1, A2) dosed at
300 mg/kg and three females (A9, A10, A12) dosed at 2000 mg/kg.
All remaining animals were considered to have achieved satisfactory bodyweight gains
throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study
termination on Day 15.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal oral dose (LD50) to rats of Ferrophosphorus (Fe3P) was
demonstrated to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
04 April 2011 - 11 May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to official EC and OECD test guidelines, and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, 12 NohSan No. 8147
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:UK
- Age at study initiation: 49-56 days
- Weight at study initiation: 301-330 g (males) and 202-222 g (females)
- Housing: The animals were housed five of one sex per cage during the main study. The cages were made of a polycarbonate body with a stainless steel mesh lid. Wood shavings (Lignocel 3/4) were used as bedding and were sterilised by autoclaving and changed at appropriate intervals each week. Cages, food hoppers and water bottles were changed at appropriate intervals.
- Diet (e.g. ad libitum): Standard rodent diet (Rat and Mouse No. 1 Maintenance Diet). This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 23°C
- Humidity (%): 40 - 70%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12hrs light

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: ADG snout-only inhalation exposure chamber, restraining tubes, a dust generator (to produce an aerosol from the powder supplied), air supply to the dust generator and extract lines, which attached to the top and bottom of the chamber respectively. A filtration system was incorporated in the extract line.
- Exposure chamber volume: ca. 30 litres
- Method of particle size determination: Cascade Impactor
- Temperature, humidity, pressure in air chamber: 20.6-25ºC, 36.2-58.9%,

TEST ATMOSPHERE
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 8.0µm/2.64σg

Analytical verification of test atmosphere concentrations:
yes
Remarks:
Atmosphere samples and particle size distribution samples were determined by gravimetric analysis.
Duration of exposure:
4 h
Concentrations:
0 (Group 1) and 5 (Group 2) mg/L
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the observation period, the animals were observed once in the morning and once toward the end of the experimental day. On the day of termination observations were recorded in the morning only.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observations (at least twice daily through the observation period), mortality (all cages checked at least twice daily), bodyweight (The weight of each animal was recorded on Day 1 (prior to dosing), 2, 4, 8 and 15).
Preliminary study:
In view of the limited data toxicity available, and as allowed for in the regulatory guidelines a preliminary exposure, using 1 male and 1 female rat, was conducted at the target (Limit test) concentration of 5 mg/L for a period of 4-hours in order to assess the likely response of rats to the test substance. As a concentration of 4.91 mg/L was tolerated by the preliminary animals, the main study test animals were also exposed to the target concentration of 5 mg/L for a period of 4-hours.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.75 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The individual and mean achieved aerosol concentration values are higher than the target of 5 mg/L. The highest achieved chamber aerosol concentration was 9.35 mg/L. The lowest value was 4.87 mg/L.
Mortality:
There were no unscheduled deaths.
Clinical signs:
Grey staining of the head was evident for all Group 2 animals during exposure and was also apparent immediately after exposure, in conjunction with grey staining to the forepaws which was present for the majority of Group 2 animals. The grey staining was no longer evident at the initial check on Day 2 and Day 3 for males and females respectively.
The clinical sign of wet fur was considered to be related to the restraint procedure, including a proportion of control group animals, however the incidence and persistence of wet fur was noted to be greater for Group 2.
Body weight:
There were no treatment related effects on bodyweight.
Gross pathology:
The macroscopic examination performed after a single exposure and a 14 day observation period revealed the following intergroup differences:
- A dark (brown) appearance of the lungs was evident in all Group 2 animals.
- Enlargement of the tracheobronchial lymph nodes was observed in two males and all females of Group 2.
- The nature and incidence of all other findings were consistent with the commonly seen background of macroscopic changes.
Other findings:
- Organ weights:
- Other observations: Group mean lung weights for Group 2 were higher when compared with Controls, 1.49 X and 1.46 X for males and females respectively.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LC50 (4 hour) of Fe3P is in excess of 5.75 mg/L for male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An acute oral toxicity study in rats was conducted (Huntingdon Life Sciences, 2010) to determine the acute LD50 of Fe3P when administered orally. The study was conducted according to EC test guideline B1, OECD guideline 423, and US EPA and Japanese test guidelines, and in compliance with GLP.

Two groups of three fasted female rats received a single oral gavage dose at 300 mg/kg bodyweight; as the results at this level indicated that the LD50 was greater than 300 mg/kg bodyweight, a further two groups of three fasted females received a single oral gavage dose of 2000 mg/kg bodyweight.

There were no deaths during the study. The only clinical sign of a reaction to treatment noted during the observation period was abnormally coloured faeces (black) seen in all animals dosed at 300 mg/kg, and three females dosed at 2000 mg/kg; these signs had resolved by day 2 of observation. A low bodyweight gain was observed late in the observation period for two animals at 300 mg/kg and three animals dosed at 2000 mg/kg. No abnormalities were noted in any animal during the macroscopic examination at study termination.

The acute median lethal oral dose to rate was demonstrated to be greater than 2000 mg/kg bodyweight.

An acute inhalation toxicity study in rats was conducted (Huntingdon Life Sciences, 2011) to determine the acute LD50 of Fe3P by inhalation exposure. The study was conducted according to EC test guideline B2, OECD test guideline 403, and US EPA and Japanese test guidelines, and was performed in compliance with GLP.

1 control group and 1 test group each consisting of 5 male and 5 female Sprague Dawley rats were administered a single 4 -hour snout-only exposure, then observed over 14 days prior to sacrifice and macropathological examination. The time-weighted average aerosol concentration of Fe3P in the treated group was 5.75 mg/L, which was close to the target concentration of 5 mg/L. Individual and mean calculated Mass median aerodynamic diameter (MMAD) values were above the optimal range of 1 - 4 µm; the average MMAD was 8 µm.

There were no unscheduled deaths during the study. Clinical signs were limited to grey staining of the head in all animals of the treated group, and the forepaws in the majority of animals in the treatment group. This was no longer evident at the first check during the observation period. There were no treatment related effects on bodyweight. Macroscopic pathological examination following sacrifice revealed a dark brown colour in the lungs of treated animals, a higher relative weight of lungs in the treated group by comparison to the control group, and enlarged tracheobronchial lymph nodes seen in treated animals.

The LC50 (4 hour) in rats of Fe3P was found to be greater than 5.75 mg/L under the conditions applied during this test.

Justification for classification or non-classification

The oral LD50 in rats of Fe3P was determined to be greater than 2000 mg/kg bodyweight. According to both the Classification Labelling and Packaging Regulation (CLP, EC number 1272/2008) and the Dangerous Substances Directive (DSD, Directive 67/548/EEC), classification for acute oral toxicity only applies where the oral LD50 in rats is equal to or less than 2000 mg/kg bodyweight; on this basis Fe3P is not classified for acute oral toxicity.

The inhaled LC50 in rats of Fe3P was determined to be greater than 5 mg/L. According to both the CLP Regulation and the DSD as above, classification for acute oral toxicity only applies where the inhaled LC50in rats is equal to or less than 5 mg/L; on this basis Fe3P is not classified for acute inhaled toxicity.

Although the studies noted above were designed to determine the lethal dose / concentration of Fe3P, and signs of sublethal toxicity were not observed in detail, the macroscopic pathology in each case did not indicate Specific Target Organ Toxicity (STOT, single exposure) by either administration route. The differences between the lungs of the treated group animals and the control group animals seen in the acute inhalation study (Huntingdon Life Sciences, 2011) were expected, and relate to the presence of test material in the lungs of the treated animals (increased lung weights and dark brown colour in the lungs) and the elimination response (enlarged tracheobronchial lymph nodes); these observations are not indicators of toxicity.

On this basis, Fe3P is not classified for STOT following single exposure by either the oral or inhaled exposure routes. As no data is available for dermal exposure, the classification of Fe3P for single-exposure STOT cannot be considered conclusive.