Sodium 1-amino-9,10-dihydro-4-[5-[(2-hydroxyethyl)sulphamoyl]-3,4-xylidino]-9,10-dioxoanthracene-2-sulphonate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

(Duration of exposure was 1 h without any justification)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

FAT 20033/L TE

IUPAC Name:

FAT 20033/L TE

Constituent 2

Reference substance name:

Sodium 1-amino-9,10-dihydro-4-[5-[(2-hydroxyethyl)sulphamoyl]-3,4-xylidino]-9,10-dioxoanthracene-2-sulphonate

EC Number:

247-269-2

EC Name:

Sodium 1-amino-9,10-dihydro-4-[5-[(2-hydroxyethyl)sulphamoyl]-3,4-xylidino]-9,10-dioxoanthracene-2-sulphonate

Cas Number:

25797-81-3

Molecular formula:

C24H23N3O8S2.Na

IUPAC Name:

sodium 1-amino-4-({3-[(2-hydroxyethyl)sulfamoyl]-4,5-dimethylphenyl}amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

powder / dark blue

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: E01A25-11 (DCT No. 70083)
Test material is dark blue powder

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Males and Females 275 to 344 g
- Housing: Housed individually, in suspended, wire bottom cages
- Diet: Ad libitum
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: Approx. 74±1 °F (ca. 23 °C)
- Humidity: 45-55 %
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.36 µm

Details on inhalation exposure:

- Generation of test atmosphere / chamber description: This test was conducted in a 40 L (36 x 36 x 31 cm) glass exposure chamber. The sides and the bottom of the chamber had centered holes (3-4 cm in diameter) to allow access to the chamber for testing and exhaust of the atmosphere. The port in the bottom of the chamber was centered over a 10 cm hole in a wooden platform. A funnel (8.5 cm in diameter) was brought from the underside of the platform through the hole and centered on the port in the bottom of the chamber. Dynamic air flow within the chamber was maintained by connecting the funnel to a vacuum pump for continuous changing of the chamber atmosphere.

A raised, tightly-fitting, wire mesh screen was placed over the bottom of the chamber and served as flooring for the test animals. This screen also served to raise the animals to a level such that the side ports in the chamber were at the breathing level of the animals. All measurements of particle size and concentration of the test substance were made from these side ports. Also, the delivery of the test substance into the chamber was done through one of the ports on the side of the chamber. The lid of the chamber also had a port which was used (if desired) for measuring the chamber atmosphere to insure even distribution of the test substance.

- Test substance generation: The test substance was generated as a dust using a 3-neck, round-bottom, 250 mL Pyrex flask. A stirring mechanism was placed through the center neck of the flask and an air line through one of the side necks. The third neck was connected by a glass elbow (which had an air vent to allow flushing) to the chamber. The dust was introduced into the chamber through a side port. A piece of rubber was taped over the outer area around the hole and a vertical slit made in the rubber to allow the entrance of the glass elbow from the dust generator. Constant flow of material was maintained by a calibrated flowmeter connected between the air line and the generating apparatus. In all instances, the air flow was maintained at or above 0.5 L of air/minute/rat.

- Exposure monitoring: Measurement of the atmospheric concentration of test substance in the chamber was achieved using a Gelman Model 1235 stainless steel filter holder containing a pre-weighed glass fiber filter (Gelman type AE-47 mm). The filter holder was attached to a vacuum pump which was regulated to exhaust 1 L of air/min from the chamber through the filter. Subsequent weighing of the filter after a designated period permitted the calculation of the atmospheric concentration of the test substance in the chamber during the exposure. Particle size determinations were made using a Cascade Impactor.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Concentrations:

Mean achieved: 0.29±0.12 mg/L

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations:
Mortality and clinical signs- Four times during the exposure (15, 30, 45 and 60 minutes), twice after the exposure (3 and 6 h) on same day and daily once thereafter.
Body weights- pre-test, Day 1, 7 and 14
- Necropsy of survivors performed: Yes

Statistics:

no data

Results and discussion

Preliminary study:

none

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.29 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

No mortality was observed.

Clinical signs:

other: No adverse effects were noted during the 1 h exposure or during the 14 d post-exposure period.

Body weight:

All animals displayed a normal pattern of weight gain.

Gross pathology:

All organs examined were normal.

Other findings:

none

Any other information on results incl. tables

Table: Method of calculating analytical concentration

	SAMPLE 1	SAMPLE 2	SAMPLE 3	SAMPLE 4
Post Weight (mg)	1495.5	1500.3	1500.3	1495.8
Pre-Weight (mg)	1493.5	1495.9	1495.9	1493.3
Weight Difference (mg)	2.0	4.4	4.4	2.5
Flow Rate (L/min)	1	1	1	1
Sample Time (min)	10	10	10	10
Air Volume (L)	10	10	10	10
Analytical Concentration (mg/L)	0.20	0.44	0.44	0.25

 

The average mass median particle diameter was 1.36 ± 0.26 µ. The 1 h LC50 value is >290 mg/mm³ (>0.29 mg/L).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The 1 h inhalation LC50 value of the FAT 20033/D was considered to be >290 mg/mm³ (>0.29 mg/L).

Executive summary:

A study was conducted to evaluate the acute inhalation toxicity of FAT 20033/D (ca. 46 % purity) following a method comparable to EPA OPPTS 870.1300 with deviations. A single group of 10 rats (5/sex) were exposed (whole body) for 1 h to the dust of the test substance at a mean achieved concentration of 0.29 mg/L (i.e. 290 mg/m³). A 14 d observation period followed. No mortality, change in body weight, clinical signs or gross pathological organ changes were observed during the study period. Hence, the 1 h inhalation LC50 value of the test substance was considered to be >290 mg/mm³ (>0.29 mg/L).