Sodium bis[N-[7-hydroxy-8-[[2-hydroxy-5-[(methylamino)sulphonyl]phenyl]azo]-1-naphthyl]acetamidato(2-)]chromate(1-)

Endpoint summary

Key value for chemical safety assessment

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: Strudy conducted following official guidelines and GLP compliant.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Wistar rats of 8 weeks were delivered with a certificate for "quality status". The state of health was declared, stipulating that do not carry external and internal parasites, pathogens, viruses, and fungi. After transporting the animals were placed in plastic polypropylene jars breeding TA (550 x 320 x 180 mm, Velaz Praha). Each gender was housed separately conventional type cage, with automatically controlled temperature, humidity and light regimes at 22 ° C + / - 3 ° C, relative humidity 40-60% and 12 h light regime (12 hours light, 12 hours dark). Before the actual exposure the animals had at least one week recovery period. The animals were fed Mixed fodders Altromin 1320 (Velaz Praha) at a dose of 12 grams per head per day, and safe drinking water ad libitum.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

air

Details on inhalation exposure:

A "head only" equipment with the constant exchange of air in the breathing zone was used.
samples were metered by WDFU directly into the inhalation chamber where a nebulizer unit atomizationwas used so that the atmosphere inside the inhalation chamber was homogeneous. Animals were fixed in the tubes of glass with a diameter of 60 mm, so that their facial parts intervened in a glass cylinder - vertical-axis 250 mm in diameter, in which there was a dynamic exchange of atmospheric linear rate of 7 l / min.
Compressed air was drawn from the central distribution of Synthesia airflow and was measured continuously throughout the exposure. In an apparatus for maintaining negative pressure was 10 mm water column. Temperature and humidity were measured in the central part of the inhalation chamber
samples of the atmosphere inside the inhalation chamber were collected at 4 l / min, a total and the concentration of the test substance for inhalation chamber was determined gravimetrically

exposure data
The average flow of air apparatus: 0.42 m3/hr
temperature inside the apparatus: 24 ° C
relative humidity inside the equipment: 45%
actual concentration measurements 0, 7 and 14 day test: see Table C1 (Appendix C2)
The particle size of the starting material, see Table C2 (Appendix C3)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically

Duration of exposure:

ca. 4 h

Concentrations:

4.82 mg/l

No. of animals per sex per dose:

5 males and 5 females for each dose

Control animals:

yes

Sex:

female

Dose descriptor:

LC0

Effect level:

> 4.82 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC0

Effect level:

> 4.82 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no mortality was observed during the 14 days observation period

Clinical signs:

other: In the initial phase was observed an effort to escapedue to the irritating effects of dust aerosol. Animals were pulling the head deep into the tube. Later, as a result of sedimentation of the test substance on the walls of inhalation chamber monitoring

Gross pathology:

At the end of the 14 day observation period animals were sacrificed. Autopsy was performed, focusing on overall examination of the body surface and the natural orifices and cavities, macroscopic thoracic and abdominal and selected organs - the trachea, lungs, heart, thymus, liver, spleen and kidneys.
At this examination, all of the animals show diffuse dark-gray discoloration, of the lungs but total absence of other lesions. The other organs have no findings

Prior to the test, the microscopically particle size of the starting material sample ostalanova sed BL. was measured particles ranging below 4 microns. The particle size is one of the limiting factors when assessing the inhaled material in different parts of the respiratory system. In general, the biological activity of particles in the respiratory tract depends on their physical properties. The chemical nature of these particles is of secondary importance. Their size, weight, shape, surface and solubility are limiting factors. Particles larger and heavier effort to adhere to the mucosa of the upper respiratory tract (URT) - in the nasal cavity, the lining of the trachea and larger bronchial mucosa: soluble particle is dissolved in mucus HCD.

Therefore, captured particles by the mucociliar system, are expelled into the mouth and swallowed them and absorbed through the digestive tract. In the lowest lung (respiratory bronchioles, alveolar ducts bifurcation, alveoli) the smallest and lightest particles can be found. It is these particles, although there only a small fraction, that penetrate into these areas, and that are responsible for the emergence and development of lung disease caused by particles.

During the exposure to the test substance or in the course of a 14-day testing period, there were no mortalities of experimental animals. The clinical detection of bad health status can be associated both to the mechanical irritanting presence of dust particles exposed to mucous membranes and upper respiratory tract(secretion from the nasal cavity and eyes,swelling of the eyelids) as well as the bottlenecks respiratory tract,caused by accumulation of the test substance and mucus (the respiratory disorders) and by the reduced airway caused by accumulation of the test substance and mucous (respiratory failure) and by insufficient supply of oxygen deficient oxygenation of the blood to the vital organs (apathy).

 

When assessing the results of the test and their testimony in relation to possible human exposure, it is necessary to take into account size particles after their entry into the airways and total or local effects of a test substance. For experimental animals in general, the nose-breathing rodents exhibit lower pulmonary (P) and higher carrier (N) and tracheobronchial deposition than humans. Deposition in nasopharyngeal (NH) area increases substantially with larger particles and is the dominant site of deposition for particles larger than 4 microns MMAD . Udaje Raaba et al. state that particles larger than 6 microns MMAD has small P deposition while for 10 micron particle is negligible. In humans, P deposition is blocked for particles up to 10 um in nasal breathing and 15 um MMAD during oral breathing.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance was tested following OECD 403 for acute inhalation toxicity. The LC0 resulted > 4.82 mg/l for males and females.

Executive summary:

The substance was tested for acute inhalation toxicity following OECD 403. Wistar rats ( males and females) were exposed to a single concentration (in a limit test) in aerosol of the tested substance ( MMDA < 4 um) and observed for a 14 day period. No mortality was observed in any animals at the dose of 4.82 mg/l while clinical signs desapperad after 2 days (apathy, irregular breathing, no food or drink consumption, irregular movements of the forelegs). At the microscopical examination diffuse dark grey colour was found in the lungs but no lesions to these organs or to others were detected. The clinical signs were attributed to the difficulty to breath, together with mucous and consequent bad oxigenation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 820 mg/m³ air