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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. certificate)
Remarks:
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Formaldehyde
- Physical state / appearance: Liquid / colorless, clear
- Analytical purity: Formaldehyde: 10.1 g/100 g (Titration)
- Lot/batch No.: CMPKQ0901
- Expiration date of the lot/batch: 09 Apr 2015

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V. Kreuzelweg 53, 5961 NM Horst, Netherlands
- Age at study initiation: male animals approx. 9 weeks, female animals approx. 11 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight). Mean weight males 261.5 g, mean weight females 214.3
- Housing: Single housing in Type III: (polycarbonate cages) (floor area about 800 cm2) with wooden gnawing blocks (Typ NGM E-022); Abedd Lab. and Vet. Service GmbH Vienna, Austria and Play Tunnel, large (Art. 14153); PLEXX b.v., Elst, Netherlands
- Diet: Kliba laboratory diet, mouse/rat maintenance “GLP”, 10 mm pellets, Provimi Kliba SA, Kaiseraugst, Basel Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24
- Humidity (%): 30 – 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Test-substance preparation: The test substance was dosed unchanged.
- Equipment: Continuous infusion pumps PHD Ultra (Harvard Apparatus, Inc., Holliston, Massachusetts, U.S.A.); Atomization vaporizer (glass) (BASF SE, Ludwigshafen, Germany) with thermostat (JULABO Labortechnik GmbH, Seelbach, Germany)
- Generation technique: A vapor was generated. The vapor was produced by continuously pumping amounts of the test substance into the thermostated vaporizer and using compressed air. The vapor was mixed with streams of conditioned air and passed into the inhalation systems.
- Generator temperature 40°C
- Whole-body inhalation system: IKA 02 (glass-steel construction, BASF SE, volume V 200 L: the animals were kept in compartmentalized wire cages (DKIII) and were exposed inside the chamber. The homogenous distribution of test substance atmosphere in this inhalation system has been verified with model vapors.
- Conditioned air: The central air conditioning system provides cold air of about 15°C. This cold air passes through an activated charcoal filter, is adjusted to room temperature of 20 to 24°C and passes through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air was used to generate inhalation atmospheres.
- Compressed air: Compressed air was produced by an oil-free compressor (HT 6, Josef Mehrer GmbH & Co KG, Germany). For this purpose, air is filtered by an inlet air strainer and introduced into the compressor. After passing through a second ultra-filter (SMF 5/3, 108 mm, Donalson), the compressed air (15 bar) is stored in a storage of 1500 or 5000 L. The compressed air is conducted to the laboratories via pipes, where the pressure is reduced to 6 bar. In the laboratory, the compressed air can be taken as required.
- Exhaust air: The exhaust air was filtered and conducted into the exhaust air of the building. The exposure system was located inside an exhaust cabin in an air-conditioned laboratory. During exposure, the following scheduled parameters were recorded four times at about 1- hour intervals: Supply air flow (compressed air): 1.0 m³/h, plus a dilution air (condition air): 2.0 m³/h (from a central air-conditioning system). The flow was adjusted and continuously measured with a flowmeter (Yokogawa).
- Exhaust air flow:: 2.9 m³/h. The flow was adjusted and continuously measured with a flowmeter (Yokogawa). The lower amount of exhaust air, which was adjusted by means of a separate exhaust air system, achieved a positive pressure inside the exposure system. This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals.

ANALYTICAL INVESTIGATIONS:
The concentration in the inhalation atmospheres was determined by gas samples (sampled in evacuated gas container). The analysis was carried out as a separate study on site by employees of the Competence Center Analytics, BASF SE, Ludwigshafen, Germany, under the responsibility of the Study Director of this facility.
- The nominal concentration was calculated from the amount of test substance dosed and the supply air flow.
- Sampling position: immediately adjacent to the animals' noses at a separate spare port
- Sampling: Gas sample into evacuated gas sampling tubes (glass)
- Mean and standard deviation were calculated for the concentration from the results of the 8 individual measurements.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
Plus equilibration time of the inhalation systems (t99 about 18 min).
Concentrations:
463 ppm (analytical concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: at least 14 days
- Body weight determination: Individual body weights once during the acclimatization period, shortly before exposure (day 0) and at least on days 1, 3 and 7, and before the sacrifice of the animals at the end of the observation period. Additionally, body weight was measured in animals that died from study day 1 onwards.
- Signs: Clinical observations were recorded for each animal separately several times during exposure and at least once daily on the pre-exposure day and during the observation period.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Pathology: At the end of the observation period the surviving animals were sacrificed with CO2-inhalation in a chamber with increasing concentration over time, and were subjected to gross-pathological examination as well as the animal which died.
Statistics:
For results of the type ”LC50 greater than”, ”LC50 approx.”, or ”LC50 smaller than”, the binomial test was used for statistical evaluation.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
< 463 ppm
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals died on study day 1 or 2
Clinical signs:
Clinical signs of toxicity in animals comprised gasping, respiration sounds, breathing in stretched position, closed eyelid, red discharge and red encrusted nose, poor general condition, salivation, piloerection and yellow discolored fur. Findings were observed from hour 1 of exposure until the death of the animals.
Body weight:
The mean body weights of the animals surviving the exposure period decreased until death.
Gross pathology:
During necropsy all animals showed dilated stomach, which were filled with gaseous content. Four males and four females additionally showed similar findings in the intestine. Moreover, two males showed effusion (clear fluid) in the thoracic cavity.

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria