Disodium 6-hydroxy-5-[[4-[[4-(phenylamino)-3-sulphonatophenyl]azo]naphthyl]azo]naphthalene-2-sulphonate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14.09. – 28.09.1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

OECD Guideline for Testing of Chemicals, 1981

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 6-hydroxy-5-[[4-[[4-(phenylamino)-3-sulphonatophenyl]azo]naphthyl]azo]naphthalene-2-sulphonate

EC Number:

228-412-8

EC Name:

Disodium 6-hydroxy-5-[[4-[[4-(phenylamino)-3-sulphonatophenyl]azo]naphthyl]azo]naphthalene-2-sulphonate

Cas Number:

6262-07-3

Molecular formula:

C32H23N5O7S2.2Na

IUPAC Name:

disodium 6-hydroxy-5-[[4-[[4-(phenylamino)-3-sulphonatophenyl]azo]naphthyl]azo]naphthalene-2-sulphonate

Test material form:

solid: particulate/powder

Details on test material:

Other name: Midlonová čerň VLCompany No. of sample 16/94Stored in the laboratory at room temperature before and during the experiment.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: breeding farm VELAZ Praha- Females (if applicable) nulliparous and non-pregnant: yes- Microbiological status of animals, when known: delivered with veterinary attest “QUALITY STATUS” – no parazites, pathogen microorganisms, viruses or mold- Age at study initiation: 8 weeks- Weight at study initiation: tested animals; males: 170.8 ± 7.12 g; females: 161.2 ± 4.22 g- Housing: 5 animals in 1 polypropylene cage T4 type (VELAZ), separated male/female - Diet (e.g. ad libitum): granulated mixture Altromin 1320 (VELAZ Praha); dose: 12g/animal/day- Water (e.g. ad libitum): ad libitum- Acclimation period: 1 week as minimumENVIRONMENTAL CONDITIONSAutomatically controlled temperature, humidity and lighting - Temperature (°C): 22±3 - Humidity (%): 40 – 60% - Air changes (per hr): not specified- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

air

Remark on MMAD/GSD:

see tables in attached pdf file

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION - Exposure apparatus: chamber "head only" type - Exposure chamber volume: dynamic air flow 10 L/min - Method of holding animals in test chamber: glass tubuses of 60 mm diameter - Source and rate of air: central source of pressure air, flow rate was measured continually - System of generating particulates/aerosols: WDFU (Wright Dust Feed Unit MK2, GA 4170, L.Adams, London) - Method of particle size determination: microscopically - Temperature, humidity, pressure in air chamber: 24 °C and humidity 45% (measured in middle part of chamber); negative pressure 98.07 Pa TEST ATMOSPHERE - Brief description of analytical method used: The samples of atmosphere inside the chamber were taken at a rate of 4L/min, total amount 10 L of air/sample.The air samples were passed through a collecting cartridge filled with filter material and the concentration of the test substance inside the inhalation chamber was determined gravimetrically. - Samples taken from breathing zone: yes VEHICLE - Composition of vehicle (if applicable): air - Concentration of test material in vehicle (if applicable): 5.2 mg/L of air TEST ATMOSPHEREBefore starting the exposure a particle size of the initial sample was measured microscopically. The size of the majority of particles was between 2- 4 µm. (see tables in attached pdf file)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.2 mg/L of air

No. of animals per sex per dose:

5 male/5 female

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days - Frequency of observations and weighing: immediately after end of exposure, after 1st and 2nd hour, then dailybody weight was measured immediately before exposure, then on the 7th and 14th day - Necropsy of survivors performed: yes - Other examinations performed: clinical signs, body weight, food and water intake, appearance of hair, skin and visible mucous membranes, somatomotor and mental activity, reaction to stimuli, focusing on sensibility and reactivity, lacrimation, functional assessment of the respiratory, circulatory, digestive and urogenital system

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.2 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no

Clinical signs:

other: During exposure examinationAfter 20 minutes exposure: black discharge from the nasal cavity. No motor disorders of the body have been observed.During post exposure period0, 60 and 120 min post exposure: black discharge from the nasal cavity and eyes, tro

Body weight:

see attached document Midlonová čerň VL_acute toxicity inhal_tables

Gross pathology:

The results of the limit test revealed the P-deposition with test substance particles but did not reveal any adverse effects on the health of the experimental animals. Differences in relation with the sex of the animals were not recorded. Reactions and autopsy findings were the same.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A limit test for acute inhalation toxicity with substance Midlonová čerň VL was performed. During the exposure and during the 14-day observation period there was no death among tested animals.Clinical examination of health condition suggests a mechanical irritation due to test substance on exposed mucous membranes of the upper respiratory tract, reduced airway patency and insufficient oxygen supply to vital organs.The results of the pathological-anatomical examination revealed a P-deposition of inhaled material particles without local or general response of the organism of tested animals.Differences in relation with the sex of the animals were not recorded. Reactions and autopsy findings were the same.The results of the limit test revealed the P-deposition with test substance particles but did not reveal any adverse effects on the health of the experimental animals.

Executive summary:

A limit test for acute inhalation toxicity with substance Midlonová čerň VL was performed. The test was performed according to OECD TG 403 methodology. Experimental animals (10 rats Wistar) were exposed to an aerosol inhalation of the test substance powder in air for 4 hours in the "head only" inhalation chamber. Actual test substance concentration was measured by a gravimetric method. Prior to exposure, the particle size of the initial sample was measured microscopically. The particle size was predominantly within the range 2- 4 µm. Particle size is one of the limiting factors in the deposition of inhaled material in different areas of the respiratory apparatus.

During the exposure and during the 14 day observation period there was no death among tested animals.

Signs of intoxication were clinically determined and give an evidence of mechanical irritation of dust aerosol on exposed mucous membranes of the upper respiratory tract, reduction in airway patency and insufficient oxygen supply to vital organs.

Pathological examination demonstrated a focal infiltration of pulmonary tissues by test substance particles.