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Administrative data

Description of key information

The test item was tested in two acute oral studies and in two acute inhalation studies. The test item revealed an oral LD50 of 26.15 mg/kg bw in rats. The LC50 in an acute inhalation study was 7.7 mg/L.

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: no GLP study No OECD and EU guidelines were followed.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: a) Range finder: Initially, groups of two rats were given a single oral dose of the undiluted test material by gavage using an all metal stomach tube.
b) Animals were each given a single oral dose of the test material at the specified level. animals were observed at 1/4, 1 and 4 hours after treatment and then once daily for fourteen days and the mortalities recorded. Evidence of overt toxicity was also noted.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: A . Tuck and Sons Limited, Battlesbridge, Essex
- Weight at study initiation: 150 - 300 g
- Fasting period before study: yes, overnight
- Housing: Animals were housed by sex in suspended metal cages with mesh floors. A maximum number of five rats were housed in each cage.
- Diet: ad libitum, Rat Diet, supplied by Nottingham University, School of Agriculture, Sutton Bonington, Nr . Louqhborough, Leics .
- Water: water (mains tap), ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 3°C
- Air changes (per hr): a minimum of 20 air changes per hour
- Photoperiod (hrs dark / hrs light): the lighting cycle was 14 hours on, 10 hours off
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: a) range finder: 0.05, 0.125, 0.25 mL/kg; b) main test: 0.058, 0.05, 0.085, 0.146, 0.25 mL/kg
- Amount of vehicle: 400 mg/mL
Doses:
a) range finder: 20, 50, 100 mg/kg bw
b) main test: 11.69, 20, 34.2, 58.5, 100 mg/kg bw
No. of animals per sex per dose:
a) range finder: 1
b) main test: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (main test)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
26.15 mg/kg bw
Based on:
test mat.
95% CL:
20.41 - 33.51
Clinical signs:
No overt signs of toxicity were oberseved in any of the animals dosed at 11.69 mg/kg bw. At the 20.0 mg/kg bw and 34.2 mg/kg bw dose levels symtoms consisted of subdued activity, pilar erection and anorexia. Survivors at both dose levels showed a marked reduction in bodyweight gain throughout the fourteen day observation period, and two rats at 34.2 mg/kg bw showed pilar erection to days 12 and 14 respectively.
Symptoms at the 58.5 mg/kg bw level consisted of subdued an activity, pilar erection and collapse prior to death. Similar effects were observed in the 100 mg/kg bw group with animals also showing body tremors 4 hours after dosing.
Gross pathology:
Survivors at 20.0 mg/kg bw and 34.2 mg/kg bw showed evidence of anorexia, that is significantly reduced bodyweight gain. Gross necropsy of survivors (one male and one female from each group)revaled no abnormal macroscopic lesions.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
26.15 mg/kg bw
Quality of whole database:
no GLP study; no OECD and EU guidelines were followed but scientifically well documented. (Klimisch 2)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented, scientifically acceptable study report; no standard test system (exposition time: 10 min, 30 min)
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Exposition time: 10 min, 30 min
GLP compliance:
no
Test type:
other: inhalation hazard test
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: about 8 - 9 weeks
- Weight at study initiation: males 264 g, females 177 g
- Housing: wire mesh cage ( Becker, D III); in groups of three
- Diet: KLIBA 24-343-4 rat/mouse laboratory diet, 10 mm pellets, Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland, ad libitum in the exposure-free period.
- Water: Ad libitum in the exposure-free period.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12 h light and 12 h dark
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged
Details on inhalation exposure:
The product was filled to a height of 5 cm in a glass bottle (fritted glass flask, pore-size 90 - 150 um, diameter 30 mm), and the weight was determined.
A stream of 200 L/h compressed air was supplied to the fritted glass flask containing the product, which had been placed in a water bath maintained at 20°C by a thermostat. The mixture of air and test substance generated in this way was passed through a glass distributor to 6 glass tubes in which 3 male and 3 female animals had been placed. The emerging mixtures of test substance and air were exhausted.
The test substance template was used for the whole study period (30 and 10 minutes).
Suitable measures were applied to ensure that the air supply had the same temperature as in the laboratories, so that the temperature in the exposure apparatus was between 19 and 25°C.
The exposure time was 10 and 30 minutes. The intention was to determine the exposure time which was survived by all the animals, including an observation period lasting 18 days.
The amount of test substance used was determined by reweighing the fritted glass flasks. The nominal concentration was calculated from the amount of test substance consumed and the air volume.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
10 - 30 min
Concentrations:
The mean concentration of the test substance (calculated for a study duration of 10 min) was 90.01 mg/L.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 18 days
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical examinations took place each workday. Lethality was checked each day. The animals sacrificed with carbon dioxide at the end of the observation period were subjected to a gross-pathological examination.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 90.01 mg/L air
Based on:
test mat.
Exp. duration:
10 min
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 90.01 mg/L air
Based on:
test mat.
Exp. duration:
10 min
Sex:
male/female
Dose descriptor:
LC0
Effect level:
< 90.01 mg/L air
Based on:
test mat.
Exp. duration:
30 min
Sex:
male/female
Dose descriptor:
LC50
Effect level:
< 90.01
Based on:
test mat.
Exp. duration:
30 min
Mortality:
10 min exposure: no deaths
30 min exposure: 4/6
Clinical signs:
During exposure: attempts to escape, eyelid closure, dypsnea, nasal secration, missing pain reflex, watery eye secretion, salivation; 30 min exposure: frothing in the snout region, spasms.
Afer exposure: intermittently breathing, gently breathing sounds, watery eye secretion, salivation, unsteady gait, reduced general state, partly reddenish-crusted noses and orbital margins (blood test positive). 30-min exposure: One animal showed a pinpoint, smoky clouded cornea (right eye) and a dot-shaped turbidity (left eye). 10-min exposure: all animals were without findings after the 4th observation day.
Gross pathology:
Animals that died: general congestive hyperemia; lung - acute low-grade flatulence.
Sacrified animals without findings.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
7.7 mg/m³
Quality of whole database:
well-documented, scientifically acceptable study report
OECD guideline was followed.
No GLP study.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

In the key study, the test item was tested in 5 male and 5 female Sprague Dawley rats in dose of 11.69, 20, 34.2, 58.5, 100 mg/kg bw. The acute oral median lethal dose (LD50) of the test item in the rat, was found to be 26.15 (20.41 - 33.51) mg/kg.

In the supporting study, the test item was tested in 5 male and 5 female Wistar rats about 14 day obersevation period in dose of 178, 261, 383, 562 and 825 mg/kg bw.The test item revealed an oral LD50 of 329 mg/kg bw in male/female rats, an oral LD50 of 383 mg/kg bw in male rats and LD50 of 289 mg/kg bw.

Acute inhalation study:

In the key study, the test item was tested in 5 animals according to OECD guideline no. 403. The concentrations were 2.5 and 7.7 mg/L. The LC50 in an acute inhalation study was 7.7 mg/L.

In the supporting study, the test item was tested in groups of 3 Wistar rats in no standard test system (the exposition time: 10 min, 30 min). The LC0 (30 min) and the LC50 were smaller than 90.01 mg/L The LC0 (10 min) and the LC 50 (10 min) were greater than 90.01 mg/L.


Justification for selection of acute toxicity – oral endpoint
One key study is available.

Justification for selection of acute toxicity – inhalation endpoint
One key study is available.

Justification for classification or non-classification

Acute oral toxicity:

Based on the results of the acute oral toxicity study, the substance was classfied and labelled as Acute tox. 2 (H300: Fatal if swallowed.) according to Regulation (EC) No 1272/2008 (CLP) and as T, R25, Toxic if swallowed. according to Directive 67/548/EEC (DSD).

Acute inhalation toxicity:

Based on the results of the acute inhalation toxicity study, the substance was classfied and labelled as Acute tox. 3 (H331: Toxic if inhaled.) according to Regulation (EC) No 1272/2008 (CLP) and as Xn, R20 Harmful by inhalation. according to Directive 67/548/EEC (DSD).