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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April-May 1987
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Relatively well reported study with some doubts on the results of the particle szie measurements, which, however, do not invalidate the outcome of the study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Guideline was not mentioned in the report.
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Reference substance name:
Acetic acid, oxo-, sodium salt, reaction products with cresol and ethylenediamine, iron sodium salts
EC Number:
EC Name:
Acetic acid, oxo-, sodium salt, reaction products with cresol and ethylenediamine, iron sodium salts
Cas Number:
Molecular formula:
non specified (UVCB substance)
non specified (UVCB substance)
Details on test material:
Name of test compound: Bolikel FE
Amount delivered: 4 x 375 g
Appearance: brown/red crystalline powder
Batch no: 2
Receipt: 27 February 1987
Storage: room temperature

Test animals

other: CD (remote Sprague Dawley origin)
Details on test animals or test system and environmental conditions:
- Source: Charles River UK Ltd.
- Age at study initiation: 6-11 weeks on arrival, 7-12 weeks at start
- Weight at study initiation: 251-273 g (males) and 235-250 g (females)
- Fasting period before study: ca. 17 h
- Housing: in polypropylene cages with stainless steel grid floors and tops; 5 per sex
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: ca. 1 week

- Temperature (°C): targeted at mean of 22 and range of 19-25
- Humidity (%): targeted at mean of 55 and range of 40-70
- Air changes (per hr): ca. 17
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 April To: 21 May 1987

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
other: air
Details on inhalation exposure:
- Exposure apparatus: 30 cm diameter alumnium ally cylinder with a volume of ca. 60 L containing 3 exposure sections with 20
animal ports each. Chamber and dust generator were placed in a large cabinet equipped with an extract fan
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: in restraining tubes
- Source and rate of air: dry, oil free, compressed air
- Method of conditioning air: no info except that air was dry and free of oil
- System of generating particulates/aerosols: Wright dust feeder, flow rate 25 L/min. Test material was first conditioned by a single pass through the 1 mm screebn of an ultracentrifugal mill
- T90 (theoretical time to reach 90% of the final concentration): 5.5 min; thereafter exposure was timed for 4 h
- Method of particle size determination: 2 times per h; cyclone sampler (at 2 L/min to obtain the fraction of particles that had an
Equivalent Aerodynamic Diameter < 5 micrometer), and a 5-stage cascade impactor (Casella) (at 17.5 L/min)
- Treatment of exhaust air: via absolute filter, also at a rate of 25 L/min
- Temperature, humidity, pressure in air chamber: T = 21.6±0.33 degrees C, RH = 63±2%, zero pressure difference between
chamber and extract cabinet air

- Brief description of analytical method used: gravimetry, 2 times per h, 2 L/min
- Samples taken from breathing zone: yes (spare animal port)


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The cyclone method showed that on average 80.7±4.3% of the particle mass had an aerodynamic
equivalent diameter< 5.0 microns, indicating that a large fraction of the particles was respirable.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMEAD (Mass Median Equivalent Aerodynamic
Diameter) was reported to be 0.274 microns (GSD not indicated).
The latter value is considered unreliable (also because of lack of data) because:
- if almost 81% of the particles < 5 microns and therefore 19% > 5 microns, it is not likely to obtain an MM(E)AD of 0.274 micron
(indicating that 50% of the particles was smaller than 0.274 microns). This is only possible when particles (or better: agglomerates of particles) break up in the cascade impactor or that the test material is rather fluffy in air.
- no indication was given on the cut-off value for each stage of the cascade impactor (missing info to better judge on the validity of the results of the particle-size measurements)
- on average 62% was found on the last stage (i.e. the back-up filter). This would mean that a substantial fraction of the test
particles had just 'flown' through the cascade impactor, which normally only happens with very fluffy material (such as amorphous silica), or that agglomerates may have been broken up.

Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
Actual concentration 1.24±0.052 mg/L (stated to technically highest attainable concentration)
Nominal concentration: 8.44 mg/L
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 1 (day of exposure), 2, 3, 4, 5, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: absolute and relative weight of liver, kidneys and lungs
Not required

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 1.24 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: technically highest attainable concentration
Clinical signs:
other: During exposure: progressive contamination of the fur on the head and abdomen was observed for all rats After exposure: reduced motor activity was evident in all rats immediately following exposure. Subsequently the behaviour of all rats was normal throu
Body weight:
Following exposure the rate of bodyweight gain for male rats was reduced for one day. Female rats lost bodyweight or gained
weight at a reduced rate for several days. Subsequently the rate of bodyweight gain was similar to that expected for rats of this
age and strain.
Gross pathology:
The presence of test material on the fur was noted for seven rats at necropsy. Other minor macroscopic changes noted were
considered to be of spontaneous origin and unrelated to exposure to the test compound.
Other findings:
The relative lung, liver and kidney weights of all rats were within normal Iimits.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Migrated information
There were no deaths and hardly clinical signs following the exposure of five male and five female rats to Bolikel Fe at the maximum level that could be achieved in air using the methods described in this report. The median lethal concentration for four hours of
exposure (LC50 4-h) for Bolikel Fe is therefore in excess of 1.24 mg/l.
Executive summary:

The acute inhalation toxicity of Bolikel Fe was investigated by exposing a group of five male and five female rats to the maximum concentration of the test substance that could be generated. The test group was subjected to a single four-hour, continuous snout-only exposure. Signs of reaction to treatment were recorded during a subsequent 14 -day observation period. The animals were sacrificed at the end of the observation period and subjected to detailed necropsy. The actual concentration of Bollikel Fe was 1.24±0.052 mg/L, the proportion of of particles smaller than 5 micron (Equivalent Aerodynamic Diameter) was 81%. There were no deaths as a result of exposure. During exposure, progressive contamination of the fur with the test material was seen. Clinical signs during the observation period consisted of reduced motor activity in all rats immediately following exposure. Subsequently, behaviour was normal throughout the observation period. Staining of the fur by the test material was also observed following exposure and this sign persisted through the observation period in some rats. Following exposure the rate of bodyweight gain of male rats was reduced for one day. Female rats lost bodyweight or gained weight at a reduced rate for several days. Subsequently, the rate of bodyweight gain was similar to that expected for rats of this age and strain. The relative lung, liver and kidney weights of all exposed rats were within normal limits. There were no significant changes attributable to exposure to Bollikel Fe. Conclusion: The median lethal concentration of Bolikel Fe for four hours of exposure (LC50 4 -hours) is greater than 1.24 mg/L, the maximum concentration that could be achieved using the methods described in this report. Because of this maximally achievable concentration, and the absence of toxicity, the test material does not need classification for acute inhalation toxicity.