Reaction mass of diiron carbide, diiron phosphide and triiron phosphide

Acute Toxicity: inhalation

Administrative data

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:

guideline study

Remarks:

The study was conducted according to official EC and OECD test guidelines, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009-09-07

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

1993

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998-08

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, 12 NohSan No. 8147

Version / remarks:

2000-11-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of diiron carbide, diiron phosphide and triiron phosphide

EC Number:

701-438-1

Cas Number:

not applicable

Molecular formula:

not applicable (multi constituent substance)

IUPAC Name:

Reaction mass of diiron carbide, diiron phosphide and triiron phosphide

Details on test material:

- Name of test material (as cited in study report): Fe3P (Ferrophosphorus)
- Substance type: inorganic
- Physical state: grey powder
- Analytical purity: Fe: 82.9%, P: 16.0%
- Lot/batch No.: 1192691
- Expiration date of the lot/batch: 30 June 2011
- Storage condition of test material: at ambient temperature

Test animals

Species:

rat

Strain:

other: Crl:CD® (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- 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 / 12 hrs light

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

snout only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

8 µm

Geometric standard deviation (GSD):

2.64

Remark on MMAD/GSD:

The individual and mean calculated MMAD values were above the range of 1 to 4 microns which is considered to be the optimal respirable range.

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

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 5.75 (Group 2) mg/L (mean achieved aerosol concentration; target concentration: 5 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).

Statistics:

No statistical analysis was performed on this study.

Results and discussion

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.

Effect levels

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:

other: Grey staining of head (transient; evident for all Group 2 animals); grey staining of the forepaws (transient; evident for the majority of Group 2 animals); wet fur (both groups; higher incidence in Group 2) considered related to the restraint procedure.

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: 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.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

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.