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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented, scientifically acceptable study report OECD guideline was followed. No GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr . K . Thomae GmbH, 7950 Biberach
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: males 273 +/- 16.7 g and females 198 +/- 7.6 g.
- Housing: They were housed in groups of five in wire cages, type DIII, of Becker, without bedding with a day/night rhythm of 12 hours.
- Diet: KLIBA laboratory diet rat/mouse A 343 10-mm pellets
- Water: drinking water ad libitum during the post-exposure observation period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%.
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
The concentration of test group 1 (= 2.5 mg/L) was selected on the basis of the information available on the toxicity of the test substance; the remaining concentrations were selected in such a way that it was possible to determine an LC50.
A mixture of vapour and air was generated by means of a continuous infusion pump INFU 362 (INDIGEU Switzerland) and a glass evaporator with thermostat (BASF).
The supply air was conditioned via central air conditioning in such a way that there was a temperature of 19-25°C in the exposure apparatus. The inhalation mixture was offered to the animals for inhalation for 4 hours.
By means of an exhaust air system, the pressure ratios in the inhalation system were adjusted in such a way that there was a pressure slightly below the atmospheric pressure (negative pressure). This ensured that there was no contamination of the laboratory due to possible leakage from the inhalation chambers.
The nominal concentration was determined from the consumption of test substance and the air flow.
A gas chromatographical method was used for the quantitative determination of the vapour concentration.
The samples were taken up in about 45 mL DMF.
A calibration curve was prepared with the test substance in the solvent specified. The curve was calculated with a Hewlett Packard Computer Program SD 03A (curve adjustment: linear regression).
The concentrations in mg/L were calculated from the amounts determined analytically and the sample volumes of the inhalation atmosphere.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.5 and 7.7 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
After the exposure period, the surviving animals were observed for 14 resp. 18 days (2.5 mg/L).
The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were generally recorded several times during exposure and at least once each workday during the post-exposure observation period. A check for mortalities was made daily.
At the end of the observation period, the surviving animals were sacrificed with CO2 and were subjected to a gross-pathological examination like all other animals which had died before.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 7.7 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
2.5 mg/L: no deaths
7.7 mg/L: 4/10
Clinical signs:
During exposure: eyelid closure, accelerated, irregular, dragging to intermittently breathing; partly gasping; anemic aspect; watery nasal and eye secretion, salivation.
After exposure: unsteady, staggering till shaking gait accelerated, irregular, dragging breathing till gasping with breathing sounds; reddish till watery eye and nasal secretion (blood test positive); eye and nose edges reddish crusty; reduced general state; crouched position, ruffled fur.
The intensity of the symptoms was concentration-dependent.
The animals of the 2.5 mg/L group were without findings after the 11th observation day; the animals of the 7.7 mg/L group were without findings after the 8th observation day.
Body weight:
Mean body weights for male animals: at study start 273 g, after 14 days 312 g
Mean body weights for female animals: at study start 198 g, after 14 days 220 g
Gross pathology:
Animals that died: congestive hyperemia
Sacrificed animals: nothing abnormal detected

Applicant's summary and conclusion