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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: OECD 403, GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology, BASF SE
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test substance: Butandiolformal
Test substance No.: 09/0372-2
Batch No.: BU 16
Purity: 99.63 %
Homogeneity: homogeneous
Physical state/appearance: liquid/colorless, clear

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Test animals:
Age at day 0: males approx. 8 weeks, females approx. 10 weeks
Supplier: Harlan Nederland, Kreuzelweg 53, NL-5961 NM Horst
Acclimatization for at least 5 days before exposure.
Body weight at day 0: males 206.78 +/-8.55, females 228.26 +/-3.18

HOUSING AND DIET
The animals were housed in air-conditioned rooms.
Room temperature: 20-24°C
Relative humidity: 30 – 70% for relative humidity.
15 air changes per hour.
Day / night rhythm: 12 h/12 h
Number of animals per cage: Single housing or up to 5 animals
Diet: Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
Drinking water: tap water ad libitum

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF SE)
- Exposure chamber volume: 55l
- Method of holding animals in test chamber: the animals were restrained in glass tubes and their snouts projected into the inhalation system.
- Source and rate of air: compressed air, supply air flow 1.5 m³/h, exhaust air flow: 1.35 m³/h. An air change of about 27 times per hour was calculated by dividing the supply air flows by the volume of the inhalation system.
- System of generating vapor: Vaporisers (glasses with thermostat) Piston metering pump KP 2000 (Desaga/Sarstedt). The vapor was generated by supplying amounts of the test substance to the heated vaporizer by means of the pump. The vapors that developed were taken up by the supply air and passed into the exposure system. The generator temperature was 50°C.

TEST ATMOSPHERE
Nominal concentration was calculated from the amount of test substance dosed and the supply air flow.
- Brief description of analytical method used: quantitative determination of the vapor concentration by gas chromatography.
- Sampling method: Air sampler GS 312 (DESAGA) was used. A sampling probe (diameter: 4 mm) and 3 fritted glass flasks connected in series and filled with sorption solvent (methanol) were used.
- Samples taken from breathing zone: yes (immediately adjacent to the animals' noses at a separate spare port)
- Sampling flow: 1 L/min
- Sampling velocity: 1.25 m/s
- Sampling frequency: 4 samples at about hourly intervals
- Sample volume: 1 L
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
20.8 mg/l
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
To evaluate morphological changes of respiratory tract, a satellite group (3 male rats) was exposed to the test substance simultaneously with the main group animals. One male animal was exposed to fresh air and served as control animal for histological examination. The satellite animals (3 test animal + 1 control) were sacrificed on post exposure study day 2.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20.8 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs of toxicity were observed in the control animal.
In the test substance exposure group accelerated respiration (slight to moderate), unconsciousness, hyperexcitability, poor general state, unsteady gait, eye encrusted red and piloerection were observed. Findings were observed from hour 2 of exposure through to study day 1. No clinical signs and findings were observed from study day 2 onwards.
Body weight:
The mean body weights of the animals decreased during the first few post exposure observation days and increased from study day 7 onward.
Gross pathology:
No gross pathological abnormalities were detected during the necropsy in the main group animals at the termination of the post exposure observation period.
Other findings:
Pathology:
a minimal increase in the absolute (9.5%) and relative (14.4%) lung weights in animals from the satellite group was considered to be non-adverse, since no histopathological correlate was observed.
No histopathologic findings were observed in the respiratory organs, except in one male where minimal granulocytic infiltration in the larynx at level II was noted but was regarded as non-adverse.

Concentration measurements:
Nominal concentration 25.5 mg/L
mean analytical concentration 20.8 mg/L +/-1.0

Applicant's summary and conclusion

Conclusions:
Following acute inhalation exposure the test subsance is practically non toxic according to EU standards.
Executive summary:

At the limit dose of 20.8 mg/l the test substance did not result in mortality. Furthermore no signs of systemic toxicity were observed and in a satellite group no indications of respiratory irritation were detected histopathologically.