Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 March 1989 - 16 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across to similar substance. Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Justification for type of information:
See read-across justification in Section 13.
Cross-reference
Reason / purpose for cross-reference:
other: Target substance
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read across material
Justification for type of information:
See read-across justification in Section 13.
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.35 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Description: White powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 – 10 weeks
- Weight at study initiation: Males 219 - 259g; Females 228 – 251g
- Housing: The animals were housed in groups of up to five by sex in solid floor, polypropylene cages, with sawdust bedding.
- Diet (e.g. ad libitum): ad libitum. With the exception of the exposure period, free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
- Water (e.g. ad libitum): ad libitum. With the exception of the exposure period, free access to mains drinking water was allowed throughout the study.
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21°C
- Humidity (%):46 - 60% relative
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

IN-LIFE DATES: From: To: 2 March 1989 – 16 March 1989

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
INHALATION EXPOSURE
a) Atmosphere Generation
A dust atmosphere was produced using a Wright Dust Feed, controlled by a variable speed motor with the outlet nozzle located at the top of the exposure chamber.
The cylindrical exposure chamber has a volume of approximately 40 litres. The concentration within the exposure chamber was controlled by adjusting the speed of the motor and the air flow rate through the chamber. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
Compressed air was supplied by means of a Gast 2HBB-10-P25Y oil free compressor and was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 µm before it was introduced to the nebuliser.
b) Exposure Procedure
Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of the animal was exposed to the test atmosphere.
A single group of ten rats (five males and five females) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 5 mg/litre was used for the exposure. No deaths occurred and therefore no further levels were required.
c) Exposure Chamber Temperature
The temperature inside the exposure chamber was measured by a mercury thermometer located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period
d) Exposure Chamber Atmosphere Concentration
The chamber concentration was estimated at regular intervals during the exposure period. The gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period.
Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights divided by the volume of atmosphere sampled was the chamber concentration.
The nominal chamber concentration was calculated as follows:

Nominal concentration (mg/litre) = Weight of test material used (mg) / Total air flow through chamber (litres)

e) Particle Size Distribution
The particle size of the generated atmosphere of the test material inside the exposure chamber was determined twice during the exposure period, after 40 minutes and during the last hour, using a Cascade Impactor. This device consisted of four glass impactor plates and a back up glass fibre filter (Gelman Type A/E, 25 mm) housed in an aluminium sampler. The sampler was temporarily sealed in a vacant port in the animals' breathing zone. Exposure chamber air was drawn through the Cascade Impactor using a vacuum pump for a suitable time period.
The impactor plates were weighed before and after sampling and the weight of test material, collected on each stage, calculated by difference. From the results obtained the weight distribution of particles in the size range > 13 µm, 4.0 - 13 µm, 1.7 - 4.0 µm and < 1.7 µm was calculated.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
The actual concentration of the test material was measured at least every 15 minutes during each exposure period.
The mean value obtained was 4.35 mg/litre (standard deviation of 1.28, nominal mg/litre 27.4)
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
Observation of the Animals
All animals were observed, for clinical signs, at hourly intervals during the exposure, one hour after termination of the exposure and subsequently once daily for 14 days. Any deaths and evidence of overt toxicity were recorded at each observation. Additional death checks were performed at appropriate intervals.
Individual bodyweights were recorded on the day of exposure, days 7 and 14 and at death.
At the end of the 14 day observation period, the animals were killed by intraperitoneal overdose of sodium pentobarbitone (Euthatal, 200 mg/mL, May & Baker Limited, Dagenham, Essex, U.K.). All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
Evaluation of Data
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.
Clinical observations, bodyweight and necropsy data were examined for any adverse but non-lethal effects resulting from treatment.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.35 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred
Clinical signs:
other: Isolated incidents of hunched posture, pilo-erection and occasional body tremors were noted following removal from the exposure chamber, with an isolated incident of hunched posture one hour later. All other effects noted during this period were considere
Body weight:
All animals showed expected gain in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.

Any other information on results incl. tables

 Exposure Chamber Atmosphere Concentration:

Atmosphere Concentration

Group Number

Mean Achieved (mg/litre)

Standard Deviation

Nominal (mg/litre)

1

4.35

1.28

27.4

 

Particle Size Distribution:

Group Number

Respirable Fraction (<4µm)

Mean Mass Median % Aerodynamic Diameter (µm)

Geometric Standard Deviation (µm)

1

72.2

2.9

0.58

 

Mortality Data:

Group Number

Mean Achieved Atmosphere Concentration (mg/litre)

Deaths

Male

Female

Total

1

4.35

0/5

0/5

0/10

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 of the test material in the Sprague-Dawley CFY rat was greater than 4.35 mg/litre.
Executive summary:

The acute inhalation LC50 of the test material in the Sprague-Dawley CFY rat was greater than 4.35 mg/litre. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 403 "Acute Inhalation Toxicity" referenced as method B2 in Annex V of EEC Commission Directive 84/449/EEC