Registration Dossier

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:
other: 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 guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
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:
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

Administration / exposure

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).

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:
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.

Applicant's summary and conclusion

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.