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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: guideline study according OECD 403 and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Benzylalkohol
- Purity: 99.99 %
- Appearance: clear colourless liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Bor: WISW (SPF-Cpb)
- Source: Winkelmann, Borchen (Paderborn), Germany
- Age at study initiation: young adult, corresponding to body weight 2-3 months
- Weight at study initiation: 180-210 g
- Housing: conventionally in groups of 5 in Makrolon Type III cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Mode of exposure: Animals were head/nose-only exposed to the aerosolised test article in restrainers made of plexiglas. Restrainer tubes were chosen that accommodated the animal's size. Inhalation chambers used were comercially available (Fa. Rema Labortechnik, Hofheim, Germany).
- Generation of aerosol: The test substance was nebulized neat using conditioned (dry, oil-free) compressed air. To increase the efficiency of the generation of respirable particles and to prevent larger particles from entering the chamber a preseparator/ baffle system was used (Tillery et. al., Environmental Health Perspectives, 16, 1976, 25). The inhalation chamber had the following dimensions: diameter = 30 cm, height = 28 cm (Volume: 20 L). The ratio between the air supplied and exhausted was chosen so that approx. 80% of the supplied air is removed via the exhaust system.
- Generation of atmospheres: Atmospheres were generated under dynamic conditions using a binary nozzle (Fa Rema Labortechnik, Hofheim, Germany). The air supply was 10 L/min; dispersion pressure approx. 500 kPa. The achieved air exchange was approx. 30- times/hour. Under such test conditions steady state is attained within approx. 6 minutes.
- Conditioning of compressed air: Compressed air was supplied by Boge compressors and was conditioned (i.e. freed from water, dust, and oil) automatically by a VIA compressed air dryer.
- Exhaust air treatment: The exhaust air was purified via filter systems.
- Temperature and humidity measurements revealed a mean temperature of 25 °C and a rel. humidity of 34% (inhalation chamber with animals).

TEST ATMOSPHERE
- The integrity and stability of the aerosol generation and exposure system was measured by using a RAS-2 real-time aerosol photometer (MIE, Bedford, Massachusetts, USA).
- Samples taken from breathing zone: yes
- Brief description of analytical method used: Samples were collected via Florisil-filled glass tubes. The benzylalcohol was quantitatively eluated using ethanol and its concentration was determined via gas-chromatographie (FID).
- Particle size distribution: The particle-size distribution was analysed using an aerodynamic particle sizer with laser-velocimeter (TSI-APS 3300). According to this method approx. 50-60 % of the particles were < 3 µm and therefore respirable for the rat. In fact, the actual rate of particles < 3 µm should be higher; vapourisation of smaller particles during sampling leads to an artificial shift of the particle distribution towards larger particles.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.70-2.93 µm/1.58

VEHICLE
No vehicle used.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0, 3297, and 4178 mg/m³ (analytical conc.)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on exposure day and twice daily thereafter
- Frequency of weighing: prior to exposure, on 3rd and 7th post exposure-day and once weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: Investigation of reflexes was performed according to Irwin (Psychopharmacologica, 13, 1968, 222-257)
Statistics:
Based on the maximum-likelihood method according to Bliss (Q. J. Pharm Pharmacol, 11, 1938, 192-216)

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 178 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: maximum technically achievable concentration
Sex:
male/female
Dose descriptor:
other: NOAEC
Effect level:
3 297 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: piloerection and slight bradypnea after exposure at next higher concentration (4178 mg/m³) with recovery within 1 day
Mortality:
None of the animals died in the course of the study.
Clinical signs:
0 and 3297 mg/m³ air: no symptoms
4178 mg/m³ air: piloerection and slight bradypnea. Approx. 3 hours after exposure respiration frequency returned to normal. All rats were without symptoms from 1st postexposure day onwards.
Body weight:
Toxicological relevant influence on body weights were not observed.
Gross pathology:
No evidence of pathological alterations of the organs detected at gross pathological examination.
Other findings:
Examinations of reflexes on first post exposure day revealed no treatment-related findings.

Any other information on results incl. tables

4178 mg/m³ was the maximum technically achievable concentration.

NOEL = 3297 mg/m³ air (male + female rats)

The transient clinical signs observed were seen by the author as causally related to the slight irritant effect by the test article to the upper respiratory tract (reflex bradypnoea caused by sensory irritation). No indication of respiratory damaging property was found.

Applicant's summary and conclusion

Executive summary:

In a study according to OECD TG 403 groups of 5 young adult Wistar rats/sex were subjected to a single 4-hour head/nose-only exposure to aerosol concentrations of 0 (air control), 3297, and 4178 mg/m³ air and observed for 14 days post exposure. The concentration of 4178 mg/m³ was proven to be the maximum technically achievable concentration. The generated aerosol was respirable for rats.

No mortality occurred in the course of the study. Transient clinical signs (piloerection, slight bradypnoea; recovery within 1 day) were seen as causally related to the slight irritant effect of the test article to the upper respiratory tract (reflex bradypnoea caused by sensory irritation). No indication of respiratory damaging property was found in this study.

Therefore, the LC50 (4h) was concluded to be > 4178 mg/m³ air for male and female rats. No effects were noted at 3297 mg/m³ air

(Bayer AG 1990).