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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-01-20 to 1994-02-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Test article: CGA 65047 SG 100, (A-5787 A); identical to FeNaEDDHA
- Additional specification: Sequestrene 138 Fe 100 SG
- Physical state: granules; miscible in water
- Analytical purity: 100% (UVCB)
- Lot/batch No.: P.201845
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: Tif: RAI f (SPF) hybrids of RII/1 and RII/2
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Aimal Production, 4332 Stein/ Switzerland
- Age at study initiation: Young adult
- Weight at study initiation: 191 to 231 g
- Fasting period before study: prior to dosing, the animals were fasted overnight
- Housing: The animal were housed in Macrolon cages type 4, with standardized soft wood bedding; the animals, segregated by sex, were group-housed (5 animals per cage)
- Diet (e.g. ad libitum): Rat diet (NAFAG 890 Tox, NAFAG, Gossau /SG, Switzerland, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 degree C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
>= 1.75 - <= 2.35 µm
Geometric standard deviation (GSD):
>= 2.04 - <= 2.34
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose only exposure system developed by Battelle Reasarch Centre (Geneva/Switzerland) and built from stainless steel by Ciba-Geigy Engineering Dept.
- Exposure chamber volume: internal active volume less than one liter
- Method of holding animals in test chamber: The rats were placed in Macrolon animal holders (Battelle Research Centres, Geneva/Switzerland) positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol.
- Source and rate of air: The low in any individual aerosol delivery tube was standardized to 2 L/min (velocity 1.25 m/s)
- System of generating particulates/aerosols: the aerosol was generated from the solid test material by means of a brush-feed micronising jet mill. The aerosol generation system consists of a dual flexible-brush dust-feed mechanism, modified from a design by Milliman, and jet mill, redesigned from a commercial Trost Jet Mill, to be aerodynamically compatible with the brush feed and the exposure system.
- Method of particle size determination: Particle size analysis was conducted using an eight-stage cascade impactor, equiped with collection substrates punched from regenerated cellulose filters by Schleicher u. Schuell AG. Samples of 1 liter were passed through the impactor. The amount of particles in the eight size classes was determined gravimetrically.
- Treatment of exhaust air: In order to avoid rebreathing of the exhaled air, "fresh" test substance (in first-pass chamber air) was supplied to each animal via individual delivery and exhaust tubes. In addition to the necessary animal and sampling ports, identical "void" outlets were opened in proportion to the total air flow through the chamber. The exhaust air was decontaminated by subsequent passage through a Pall HDC absolute filter.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The continuity of the particle size distribution was verified by repeated analysis of the aerosol using an APS-33 Aerodynamic Particle Sizer, equipped with appropriate dilution system to avoid coincidence counts. The number distribution in 48 classes was converted to a mass distribution, based on the bulk density of the test substance, which was determined separately.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The continuity of the particle size distribution was verified by repeated analysis of the aerosol using an APS-33 Aerodynamic Particle Sizer, equipped with appropriate dilution systems to avoid coincidence counts.
Duration of exposure:
4 h
Concentrations:
4202 ± 188 mg/m3 air
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:
- clicnical symptoms and mortalities: during and after the exposure, as well as daily thereafter for 14 days
- body weight: immediately prior to exposure and on days 7 and 14 of the observation period
- Necropsy of survivors performed: yes
Statistics:
Not performed

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 200 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortalities occured upon exposure to the test item at a concentration of 4202 ± 188 mg/m3.
Clinical signs:
other: The animals of both sexes exposed to the test article experienced the symptoms piloerection and dyspnea to a similar extent. They recovered within 5 days.
Body weight:
The weight development of all animals was within normal limits.
Gross pathology:
No deviations from normal morphology could be detected in all animals.

Any other information on results incl. tables

No other information

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 for acute inhalation toxicity of FeNa-EDDHA in albino rats was found to be greater than 4200 mg/m3 air.
Executive summary:

The acute inhalation toxicity of FeNa-EDDHA in albino rats was determined according to the OECD Guideline 403 (Acute Inhalation Toxicity). Upon a four-hour acute inhalation exposure and a 14-days post-treatment observation period, no mortalities were elicited by the test item at a concentration of 4202 ± 188 mg/m3. Due to the properties of the test material, it was not possible to generate higher test article concentrations by means of standard aerosol generation equipment. The exposure to the maximum attainable concentration was thus considered a limit test as stated in the OECD test guideline 403. From the absence of mortalities it can be assumed that the LC50 to both sexes is greater than 4200 mg/m3 air.

The animals of both sexes exposed to the test article experienced the symptoms piloerection and dyspnea to a similar extent. They recovered within 5 days. At autopsy, no deviations from normal morphology could be detected in all animals.