Registration Dossier

Administrative data

Description of key information

NOAEL oral rat > 2000 mg/kg

NOAEL inhalation rat > 5000 mg/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
other: read across from analogue substance
Adequacy of study:
key study
Study period:
since 17th April 2007 to 14th May 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study well documented, test procedure in accordance with OECD 420 methods, meets generally accepted scientific principles, acceptable for assessment. GLP compliant.
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Route of administration:
oral: feed
Vehicle:
arachis oil
Details on oral exposure:
Following a sighting test in which there were no mortalities at dose level of 300 and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP at a dose level of 2000 g/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
4 females
Details on study design:
Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.
Preliminary study:
Dose level - 300 mg/kg: there were no deaths. No sign of systemic toxicity were noted during the study. The animal showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No sign of systemic toxicity were noted during the study. Black stained faeces was noted in four animals.
Body weight:
Animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necroscopy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bw.
The test material was considered to have no significant acute toxicity risk if swallowed and did not meet the criteria for classification according to EU Regulation (EC) No 1272/2008 for classification and labelling of dangerous substances.
Executive summary:

Analogue substance 4 was tested according to OECD 420.

Following a sighting test in which there were no mortalities at dose level of 300 and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP at a dose level of 2000 g/kg bw.

Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

LD50 of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bw and therefore can be

considered as non toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
other: read across from analogue substance
Adequacy of study:
key study
Study period:
September 27, 1994 to October 11, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Justification for Read Across will be provided in section 13.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Velaz Prague
- Age at study initiation: 8 weeks
- Supplier certification: declared that animals had not the external and internal parasites, pathogenic microorganisms, viruses and fungi.
- Housing: after transporting the animals were placed in polypropylene plastic nursery containers T4 (550 x 320 x 180 mm Velaz Prague), five animals each sex separately.
- Diet: fed with granulated mixture ALTROMIN 1320 (Velaz Prague) in a dose of 12 g per animals each day
- Water: drinking water without restrictions
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 40-60 %
- Photoperiod: 12 hours of light and 12 hours of darkness


Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: samples were dispensing by WDFU (Wright Dust Feed Unit MK2, GA 4170, L. Adams, LTD., London) to an inhalation chamber, where they w ere dispersed through the spray; the atmosphere inside the inhalation chamber was homogeneous.
- Method of holding animals in test chamber: animals were fixed in a glass tube of diameter 60 mm so that the face of the glass cylinder to interfere with the vertical axis - 250 mm in diameter- in which there was a linear dynamic atmosphere exchange at 9 l/min.
- Source and rate of air: compressed air was taken from the central distribution Synthesia. Air flow was measured continuously throughout the exposure.

TEST CONDITIONS
- The average air flow apparatus: 0.540 m3/h
- The temperature inside the apparatus: 24°C
- Relative humidity inside the apparatus: 50%
- Actual concentration: 5.16 mg/L air

TEST SUBSTANCE
- Particle size of the test substance: :
diameter 1-4 um: 78,65%
diameter 4-10 um: 16,00%
diameter 10-20 um: 4,37%
diameter >20 um: 0.98%
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
5.16 mg/l air
No. of animals per sex per dose:
5 males and 5 non-pregnant females.
Control animals:
yes
Details on study design:
- Immediately after application the animals were removed from tube, placed in breeding containers and observed.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at immediately after exposure, 7 and 14 day
- Other examinations performed: clinical diagnosis was focused on the observation of nutritional status (food intake and water), the appearance of hair and skin, visible mucous membranes, mental activity, somatomotor activity, response to stimuli, focusing on sensitization and reactivity, lacrimation, functional assessment of the respiratory, circulatory, digestive and urogenital apparatus.
- After 14 days the animals were killed and an autopsy was performed. At autopsy were examined macroscopically thoracic and abdominal organs and lungs, trachea, larynx, thymus, liver, spleen and kidneys.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: also LC0
Mortality:
During the exposure there was no mortality of animals tested.
Clinical signs:
other: Clinical signs were due to mechanical irritant effect of aerosol dust on exposed mucous membranes and upper respiratory track. The main signs were: the swelling of the eyelids, runny eyes and nasal. Motor disorders of the forelegs and of the tails were ob
Body weight:
The increase of body weight of animals tested was in according to the trend of increase of control animals.
Gross pathology:
Immediately after the 14-day observation period the animals were killed . After an autopsy was performed, focusing on the overall examination of the body surface and orifices, and macroscopic examination of the thoracic, abdominal and selected organs - trachea, lungs, heart, thymus, liver, spleen and kidneys. In one male and in one female were presents haemorrhages in the lungs. In both cases, these haemorrhages were located under the pulmonary pleura. In one female were found congested kidneys
Other findings:
Potential target organs: Trachea , lungs, heart, thymus, liver , spleen and kidneys.

Observations during the exposure:

Immediately after application the animals were removed from tubes, placed in breeding containers and observed.

Motor disorders on the body,irregular breathing were recorded.

- 60 min after application:

animals presented the same symptoms of intoxication of the first observation

- 120 min after application:

animals presented the same symptoms of previous observations

- 2 days after application:

shaggy skins, different parts of the body covered by residues of the test substance,blue urine and swollen eyelids.

- 3 days after application:

in addition to the blue color of the urine were not check for any effects .

- 4 days: apart from slight blue discoloration of urine were no clinical signs of intoxication.

- From 5 to 14 days after application: during this period there were no clinical signs of intoxication.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Analogue substance 1 was tested for acute inhalation toxicity. During the exposure or during the 14-day observation period there was no death of animals tested.
Executive summary:

Analogue substance 1 was tested for acute inhalation toxicity following OECD 403. The test was performed on 10 rats WISTAR strain, that were exposed to inhalation of dust aerosol test substance for 4 hours in the inhalation chamber. The test chemical concentration was measured gravimetric method. The size of most particles ranged from 2 to 4 µm. Particle size is one of the limiting factors in the deposition of inhaled substances in different areas of the respiratory apparatus.

During the exposure or during the 14-day observation period, there was no mortality of test animals.

Clinical signs of intoxication can be described as the result of mechanically irritating dust aerosol effect on exposed mucous membranes and upper respiratory tract (HCD).

The pathological-anatomical examination showed a infiltration of lung tissue particles of the substance tested.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Target substance can be considered to have the following results for acute toxicity oral:

No Adverse Effect level, LD50 > 5000 mg/kg.

Results on similar substance 1 and on similar substance 2 were used as support to assess the non - toxicity for the acute oral endpoint.

Based on Read Across with similar substance 1, target substance can be considered to have the following results for acute toxicity inhalation:

No Adverse Effect level , LD50 > 5000 mg/m3.

Read across is discussed more in detail in the Read Across document.

Justification for selection of acute toxicity – dermal endpoint

waiving

Justification for classification or non-classification

Substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria shown in Table 3.1.1 of CLP Regulation. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE). The limit value that can trigger to Classification is 2000 mg/Kg for oral and dermal exposure pattern and 5 mg/l for inhalation exposure pattern. Therefore no classification for acute toxicity oral and acute inhalation is warranted under Regulation 1272/2008