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Description of key information

Single oral application of gavage doses to rats and observation for 14 days: LD50 = 1620 mg/kg bw (Bayer AG 1978); no indications of toxicity were observed at the lowest dose of 1045 mg/kg bw .
Exposure of rats according to OECD TG 403 to single 4-hour aerosol concentrations up to 4178 mg/m³ air (maximum technically achievable conc., Bayer 1990 ) or at the limit dose of 5400 mg/m³ (Elf Atochem SA, 1993) and observation for 14 days: LC50 > 4178 mg/m³; no mortalities were observed and only minor symptoms.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and sufficiently documented
Principles of method if other than guideline:
10 male rats received a single oral application per gavage of 1.0, 1.2, 1.4, 1.5, 2.0 and 2.1 ml/kg bw (= ca. 1045, 1254, 1463, 1467, 2090 and 2195 mg/kg bw) of the test substance. Post-exposure period was 14 days.
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
male Wistar rats, SPF, weight 160 - 180 g; husbandry: 5 animals per cage; breeder: Winkelmann
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
single oral application per gavage (no further data)
Doses:
1.0, 1.2, 1.4, 1.5, 2.0 and 2.1 ml/kg bw (= ca. 1045, 1254, 1463, 1467, 2090 and 2195 mg/kg bw)
No. of animals per sex per dose:
10 male rats per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: start and end of study
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 according Fink and Hund, Arzneimittelforschung (1965), 15, 624
Sex:
male
Dose descriptor:
LD50
Effect level:
1.55 mL/kg bw
95% CL:
1.42 - 1.7
Remarks on result:
other: corresponding to 1620 mg/kg bw (density: 1.045 g/mL)
Sex:
male
Dose descriptor:
other: NOAEL
Effect level:
1 mL/kg bw
Remarks on result:
other: corresponding to 1045 mg/kg bw
Mortality:
dose 1.0 ml/kg bw, mortality 0/10; dose 1.2 ml/kg bw, mortality 1/10; dose 1.4 ml/kg bw, mortality 2/10; dose 1.5 ml/kg bw, mortality 6/10; dose 2.0 ml/kg bw, mortality 8/10; dose 2.1 ml/kg bw, mortality 10/10;
Clinical signs:
1.0 ml/kg bw: no clinical findings
from 1.2 ml/kg bw onwards: sedation, side and prone-position, bloody eyes and reduction of general condition
Body weight:
dose 1.0 ml/kg bw, (body weight) bw start: 176 g - bw after 14 days: 235 g
dose 1.2 ml/kg bw, (body weight) bw start: 186 g - bw after 14 days: 237 g
dose 1.4 ml/kg bw, (body weight) bw start: 177 g - bw after 14 days: 228 g
dose 1.5 ml/kg bw, (body weight) bw start: 175 g - bw after 14 days: 225 g
dose 2.0 ml/kg bw, (body weight) bw start: 175 g - bw after 14 days: 237 g
dose 2.1 ml/kg bw, (body weight) bw start: 174 g - bw after 14 days: -
Gross pathology:
no data
Other findings:
no data

no data

Executive summary:

10 male rats received a single oral application per gavage of 1.0, 1.2, 1.4, 1.5, 2.0 and 2.1 ml benzyl alcohol/kg bw (= 1045, 1254, 1463, 1467, 2090 and 2195 mg/kg bw; density: 1.045 g/ml) and were observed for 14 days. Clinical signs were observed from 1.2 ml/kg bw onwards and included sedation, side and prone position, bloody eyes and reduction of general condition. The resulting LD50 was 1.55 ml/kg bw (= 1620 mg/kg bw) (Bayer AG 1978).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 620 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
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
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)
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.

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.

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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
4 178 mg/m³

Additional information

Acute Oral Toxicity:

10 male rats received a single oral application per gavage of 1.0, 1.2, 1.4, 1.5, 2.0 and 2.1 ml benzyl alcohol/kg bw (= 1045, 1254, 1463, 1467, 2090 and 2195 mg/kg bw; density: 1.045 g/ml) and were observed for 14 days. Clinical signs were observed from 1.2 ml/kg bw onwards and included sedation, side and prone-position, bloody eyes and reduction of general condition. The resulting LD50 was 1.55 ml/kg bw (= 1620 mg/kg bw) (Bayer AG 1978).

Acute Inhalation Toxicity:

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 at 4178 mg/m³ (piloerection, slight bradypnea; 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 the study. 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).

In addition, there is another study according OECD TG 403 available, in which rats were exposed to aerosol for 4 hours at a limit dose of 5400 mg/m³ (Elf Atochem SA, 1993). No mortality was observed also in this study and no signs of intoxication were reported that could be attributed to the exposure to benzyl alcohol.

It is unclear why in the Elf Atochem SA study a higher concentration of atmosphere is achieved, whereas in the Bayer study 4178 mg/m³ turned out as the maximum technically achievable concentration. Anyway, taking also into account the vapour saturation concentration of 1223 mg/m³ at 20 °C (cp. Bayer AG 1990), the available data give evidence for a low acute inhalation toxicity of the substance.

Acute Dermal Toxicity:

No data available.


Justification for selection of acute toxicity – oral endpoint
Reliable study with granted data access

Justification for selection of acute toxicity – inhalation endpoint
Fully reliable study with maximum technically achievable concentration of 4178 mg/m³ selected. Contrary to the other reliable study also data on substance purity are given in this study.

Justification for classification or non-classification

According to legal classification (Directive 67/548/EEC, 19. ATP and Regulation (EC) No. 1272/2008) benzyl alcohol is classified as R20/22 (harmful by inhalation and if swallowed) and Acute Tox. 4 (H332 = harmful if inhaled; H302 = harmful if swallowed), respectively.

Acute Oral Toxicity:

Based on the available data and according to criteria of Regulation (EC) 1272/2008, Annex I, the available data (Bayer 1978) are in agreement with the legal classification as R22 (harmful if swallowed) or Acute Tox. 4 (H302 = harmful if swallowed).

Acute Inhalation Toxicity:

Based on the available data and according to criteria of Regulation (EC) 1272/2008, Annex I, benzyl alcohol would not be classified for acute inhalation toxicity.

Mortalities were not observed in neither of the two available acute inhalation studies (both OECD 403). The maximum concentrations were 4178 mg/m³ (Bayer 1990) and 5400 mg/m³ (Elf Atochem SA 1993). Only slight and transient clinical signs were noted in the first study at 4178 mg/m³, which was the maximum technically achievable concentration in this study (Bayer 1990). No signs of intoxication were reported in the second study at 5400 mg/m³ (Elf Atochem SA 1993). It remains unclear why in one of the two studies a higher aerosol concentration could be achieved. Anyway, according to criteria of Regulation (EC) 1272/2008, Annex I no classification would result.

Nevertheless, classification as Acute Tox. 4 (H302 = harmful if swallowed) is applied as it is consistent with the legal classification.