Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 Jan 1986 to 13 Feb 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Wistar Hoe: WISKf(SPF71)
- Source: HOECHST AG, Kastengrund, SPF-Zucht
- Age at study initiation: 8-10 weeks
- Weight at study initiation: Males: 207-225 g; Females: 170-181 g.
- Housing: In groups of five animals in Makrolon Type IV cages.
- Diet: Rat diet Altromin 1324 (Altromin-GmbH, Lage/Lippe) ad libitum
- Water: tap water ad libitum
- Acclimation period: Minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30 Jan 1986 to: 13 Feb 1986

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: Individual exposure chambers for nose-only exposure
- Exposure chamber volume: 60 l
- Source and rate of air: Air was supplied by using a compressor at 4 bar, and airflow was constantly adjusted at 800 l/h by using a rotameter.
- Method of conditioning air: Humidified air (100 l/h perfusing a gas wash bottle filled with water) was introduced into the inhalation chamber
- System of generating particulates/aerosols: The test item was injected into the airflow at a constant rate by using a continous infusion apparatus. The primary aerosol generation took place in a 10 l four-neck round-bottom flask. The secondary aerosol (smaller aerosol particulates) finally reached the inhalation chamber via a standpipe.
- Method of particle size determination: The aerodynamic diameter was determined by using the APS 33 Aerodynamik Particle Sizer (TSI Inc., St Paul). Analyses were conducted every 30 min, and hourly the data was saved. At the end of exposure the collected data was statistically evaluated and mean values and standard deviations were determined for 4 time points.
- Treatment of exhaust air: Trapped and neutralised.


TEST ATMOSPHERE
- Brief description of analytical method used: Samples of the aerosol were absorbed in acetone in 3 cascaded gas wash bottles and gas chromatographically analysed.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): The aerodynamic diameter was found to be in the range of 0.486 to > 15.4 µm
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatography
Duration of exposure:
ca. 4 h
Concentrations:
11.2 mg/l
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the exposure period the behaviour of the animals was closely monitored. Then animals were observed twice daily for clinical effects. Animals were weighed post-exposure on days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 11.2 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred during the observation period.
Clinical signs:
other: - irregular, fitfully and noisy breathing - gasping - salivation - long legged, uncoordinated- and staggering tread - prone position - retracted stomach flanks - sluggished or vanished corneal reflex and positional reflex and paw flick latency; - anaesth
Body weight:
Body weight was not effected by the treatment
Gross pathology:
Necropsy revealed no pathological findings.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for acute inhalation toxicity according to the OECD TG 403 and in compliance with GLP. No deaths occurred and clinical signs noted were reversible within 4 days post exposure. The LC50 for both males and females was found to be > 11.2 mg/l. Hence, classification according to 67/584/EEC and EC/1272/2008 is not warranted.