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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
425-240-7
EC Name:
-
Molecular formula:
C28H42O8Cl2Co2N12Zn4
IUPAC Name:
Zinc hexacyanocobaltate(III), tertiary butyl alcohol/polypropylene glycol complex

Test animals

Species:
rat
Strain:
other: Crl:CDBR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, UK
- Age at study initiation: approx. 6-7 weeks
- Weight at study initiation: weight range 180-200 g
- Housing: in groups of 5 rats in stainless steel mesh cages (55x34x20 cm)
- Diet and water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical aluminium exposure chamber
- Exposure chamber volume: approximate internal volume 40 L
- Method of holding animals in test chamber: animals were in holding tubes
- Source and rate of air: approx. 30 air changes per hour
- System of generating particulates/aerosols: Wright dust feed generator
- Method of particle size determination: Cascade impactor (Andersen 298 Marple Cascade Impactor)
- Temperature, humidity, flow rates: 20-25°C, 31-66%, , chamber flow rates were always 20 L/min.

TEST ATMOSPHERE
The concentration of the test article was determined gravimetrically.
- Samples taken from breathing zone: yes
The median value for the mass median aeodynamic diameter was 2.23 µm, GSD 2.74.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
gravimetric: 5.79 mg/L; nominal: 29.4 mg/L
No. of animals per sex per dose:
5
Control animals:
other: yes, controls were exposed to an atmosphere of filtered air
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed at hourly intervals during the exposure period and for the remainder of the working day, and once daily thereafter. Animals were examined twice daily to detect any which were dead or moribund. The body weight of each animal was recorded immediately before and after exposure, on Day 2, 8 and 15 of the study, and at necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: The lungs were weighed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 790 mg/m³ air
Exp. duration:
4 h
Mortality:
Concentration - number of deaths/number of animals in dose group
Males: 5.79 mg/L - 1/5; Females: 5.79 mg/L - 0/5
The death of one male was considered to be treatment-related.
Clinical signs:
other: Treatment related signs included lethargy, cold to touch, semi closed eyes and shallow respiration for up to 4 hours after exposure, plus hunched posture up to day 2.
Body weight:
After exposure on Day 1 and 2, treated animals lost slightly more body weight than the controls, but their body weight gain by the end of the study was comparable with that of the controls.
Gross pathology:
There were no effects other than a slight increase in the lung weights of treated animals compared to controls.

Any other information on results incl. tables

As there was only one death during the study, the LC50 was not calculable. However, it can be concluded that it is >5.79 mg/L

Applicant's summary and conclusion

Executive summary:

An acute (4h) Dust Inhalation Toxicity Study according to OECD T403 was conducted on 5 rats per sex, which were head-only exposed to a limit concentration of the test substance of 5790 mg/m³. The dust was of adequate respirability for the rats (MMAD 2.23 µm, GSD 2.74).

One treated male was found dead at the end of exposure, which was considered to be treatment-related. Treatment-related clinical signs included lethargy, cold to touch, semi closed eyes and shallow respiration for up to 4 hours after exposure, additionally hunched posture up to day 2. After exposure on Day 1 and 2, treated animals lost slightly more body weight than the controls, but this effect was resolved by the end of the study. The only finding at necropsy was a slight increase in mean lung weights. The LC50 was concluded to be > 5790 mg/m³.