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Description of key information

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1987)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl: CD.BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, UK
- Age at study initiation: approx. 5-7 weeks old
- Weight at study initiation: males 156-171 g, females 142-147 g
- Fasting period before study: from approx. 18 hours prior to dosing until 4 hours after dosing
- Housing: in groups of up to 5 rats in suspended stainless steel mesh cages (55x34x20 cm)
- Diet and water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: 1% aqueous methyl cellulose
Details on oral exposure:
Administration volume: 20 ml/kg
VEHICLE: methyl cellulose, prepared for administration as a 1% m/v suspension in water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
-Preliminary test: A preliminary investigation was conducted using two female fasted rats dosed with the test substance at 200 mg/kg bw. No death occurred.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded frequently on Day 1 and regularly for the remainder of the study (at least twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period). Rats were weighed on the day before dosing, and on Day 1 (day of dosing), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
Determination of the acute median lethal oral dose (LD50).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No animal died following a single oral administration of the test substance at 2000 mg/kg bw.
Clinical signs:
Three females showed some loss of hair from Day 2 to Day 6. There were no other clinical signs of reaction to treatment.
Body weight:
All rats achieved body weight gains during the first and second weeks of the study.
Gross pathology:
Necropsy on Day 15 revealed no macroscopic changes.
Executive summary:

A standard acute toxicity testing according to OECD TG 401 was performed on 5 male and 5 female rats, receiving each a single dose of 2000 mg/kg test substance in 1% aqueous methyl cellulose. No mortalities, effects on body weight gain or findings at necropsy were observed. Three female rats showed some loss of hair from Day 2, but this was no longer apparent after Day 6. Therefore the LD50 was found to be > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 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: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CDBR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, UK
- Age at study initiation: approx. 6-7 weeks
- Weight at study initiation: weight range 180-200 g
- Housing: in groups of 5 rats in stainless steel mesh cages (55x34x20 cm)
- Diet and water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: dust
Type of inhalation exposure:
head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical aluminium exposure chamber
- Exposure chamber volume: approximate internal volume 40 L
- Method of holding animals in test chamber: animals were in holding tubes
- Source and rate of air: approx. 30 air changes per hour
- System of generating particulates/aerosols: Wright dust feed generator
- Method of particle size determination: Cascade impactor (Andersen 298 Marple Cascade Impactor)
- Temperature, humidity, flow rates: 20-25°C, 31-66%, , chamber flow rates were always 20 L/min.

TEST ATMOSPHERE
The concentration of the test article was determined gravimetrically.
- Samples taken from breathing zone: yes
The median value for the mass median aeodynamic diameter was 2.23 µm, GSD 2.74.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
gravimetric: 5.79 mg/L; nominal: 29.4 mg/L
No. of animals per sex per dose:
5
Control animals:
other: yes, controls were exposed to an atmosphere of filtered air
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed at hourly intervals during the exposure period and for the remainder of the working day, and once daily thereafter. Animals were examined twice daily to detect any which were dead or moribund. The body weight of each animal was recorded immediately before and after exposure, on Day 2, 8 and 15 of the study, and at necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: The lungs were weighed.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 790 mg/m³ air
Exp. duration:
4 h
Mortality:
Concentration - number of deaths/number of animals in dose group
Males: 5.79 mg/L - 1/5; Females: 5.79 mg/L - 0/5
The death of one male was considered to be treatment-related.
Clinical signs:
other: Treatment related signs included lethargy, cold to touch, semi closed eyes and shallow respiration for up to 4 hours after exposure, plus hunched posture up to day 2.
Body weight:
After exposure on Day 1 and 2, treated animals lost slightly more body weight than the controls, but their body weight gain by the end of the study was comparable with that of the controls.
Gross pathology:
There were no effects other than a slight increase in the lung weights of treated animals compared to controls.

As there was only one death during the study, the LC50 was not calculable. However, it can be concluded that it is >5.79 mg/L

Executive summary:

An acute (4h) Dust Inhalation Toxicity Study according to OECD T403 was conducted on 5 rats per sex, which were head-only exposed to a limit concentration of the test substance of 5790 mg/m³. The dust was of adequate respirability for the rats (MMAD 2.23 µm, GSD 2.74).

One treated male was found dead at the end of exposure, which was considered to be treatment-related. Treatment-related clinical signs included lethargy, cold to touch, semi closed eyes and shallow respiration for up to 4 hours after exposure, additionally hunched posture up to day 2. After exposure on Day 1 and 2, treated animals lost slightly more body weight than the controls, but this effect was resolved by the end of the study. The only finding at necropsy was a slight increase in mean lung weights. The LC50 was concluded to be > 5790 mg/m³.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
5 790 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity testing (OECD TG 401, limit test) resulted in an LD50 of > 2000 mg/kg bw. No mortalities, effects on body weight gain or findings at necropsy were observed.

No dermal toxicity test is available for the substance.

An acute (4h) dust inhalation toxicity study (OECD TG 403, limit test), with particle sizes of adequate respirability for rats, revealed an LC50 of > 5790 mg/m³. One male was found dead at the end of exposure, which was considered to be treatment-related. Treatment-related clinical signs included lethargy, cold to touch, semi closed eyes and shallow respiration for up to 4 hours after exposure, additionally hunched posture up to day 2. After exposure on Day 1 and 2, treated animals lost slightly more body weight than the controls, but this effect was resolved by the end of the study. The only finding at necropsy was a slight increase in mean lung weights.

 


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
Only one study available

Justification for classification or non-classification

Not classified for acute toxicity according to Regulation (EC) No 790/2009 (Amendment to Regulation (EC) No 1272/2008) and based on the criteria set out in Annex I to Regulation (EC) No 1272/2008 or in Annex VI to Council Directive 67/548/EEC (June 1967).

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