Sodium 1-amino-4-(cyclohexylamino)-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 26 to August 15, 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 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 1-amino-4-(cyclohexylamino)-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

EC Number:

224-460-9

EC Name:

Sodium 1-amino-4-(cyclohexylamino)-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Cas Number:

4368-56-3

Molecular formula:

C20H219N2O5S.Na

IUPAC Name:

sodium 4-(4-acetamidophenyl-1-amino)-1-amino-9,10-dioxoanthracene-2-sulphonate

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOP Velaz Ltd. Praha.
- Weight at study initiation: 190-202 g.
- Housing: experimental animals were housed individually in cages made of plastic polypropylene T3, equipped with dry softwood chip which was sterilized in a hot air sterilizer HS 401 A/1 at 150°C for 90 minutes.
- Diet (e.g. ad libitum): standard commercially produced set-Mixed fodders ST-1, 20 g/animal/day.
- Water (e.g. ad libitum): drinking water according to CSN 757111 ad libitum.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 50% + 15%
- Photoperiod (hrs dark / hrs light): 12 hrs cycle dark/light
- Other: fluorescent light

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 6 cm (36 cm^2) shaved skin.
- Type of wrap if used: animals were covered with gauze, aluminum foil and adhesive tape around the perimeter of the hull. This was accompanied by a fixation bandage. The dressing was covered with adhesive tape and clamped around the periphery of the fuselage.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours.

Duration of exposure:

The duration of the exposure was 24 hours.

Doses:

logarithmic dose is 5.020 g/kg

No. of animals per sex per dose:

5 males per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations: animals were observed for clinical signs of intoxication immediately after application (after 30 minutes), 3 hours after application and once a day for 14 days.
- Frequency of weighing: the animals were weighed at the beginning and at the end of the experiment.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical diagnosis was focused on observation of the appearance of hair, skin, visible mucous membranes, nutritional status, mental activity, somatomotor activity, responses to stimuli, focusing on sensibility and reactivity, lacrimation, assess the functioning of the respiratory, digestive and urogenital system Organs and muscles were examined macroscopically. After dissection internal organs were judged according to their color, size, consistency and structure. After macroscopic assessment of internal organ (heart, lungs, liver, spleen, kidneys, adrenal glands) biometric examination was performed. If the post mortem bladder is filled with urine, the urine was biochemical tested using Heptaphan indicative strips focusing on the detection of proteins, blood sugars, ketones, bilirubin, urobilinogen and pH.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 020 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 3 514 mg/kg bw

Based on:

act. ingr.

Gross pathology:

After application of the logarithmic dose of 5.020 g/Kg the following pathological/anatomical symptoms of intoxication were observed:
hair, skin and visible: normal appearance;
subcutaneous tissue and muscle: without macroscopic pathomorpholoical change;
nutritional status: very good;
head and neck: without macroscopic pathomorpholoical change;
heart: maroon (brownish-red), stiff consistency, without pathomorpholoical changes;
lung: a pinkish color, spongy, airy, without macroscopic pathomorfological changes;
stomach: filled with mushy food, without macroscopic pathomorfological changes;
intestine: filled with sparse food, without macroscopic pathomorfological changes;
liver: dark brownish color, stiff consistency, without pathomorfological changes;
spleen: reddish-brown color, stiff consistency, without pathomorfological changes;
kidneys: brownish red color, firmer texture, smooth surface, pathomorphological changes;
bladder: no macroscopic pathomorfological changes;
peritoneum: without pathomorfological changes.

Other findings:

Organ weights: the relative weight of the organs (heart, lungs, kidneys, liver, spleen, adrenal lang, testicles) of the animals assigned to the experimental group was higher than the relative weight of the organs of the animals assigned to the control group.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (male rats) > 5020 mg/kg b.w. (> 3514 mg/kg b.w. based on the active ingredient)

Executive summary:

The substance has been tested for acute toxicity by dermal route according to the OECD Guideline 402. Five Wistar rats were tested with the dose: 5.020 g/Kg. After 14 days of the observation period, rats showed increase of body weight. At the end of the experiment the relative weight of the organs (heart, lungs, kidneys, liver, spleen, adrenal lang, testicles) of the animals assigned to the experimental group was higher than the relative weight of the organs of the animals assigned to the control group.

The clinical signs observed after the application of the test material was the pinkish coloration of the skin which derived from physiological standards. After the application of the test material and the autopsy no macroscopic pathomorfological changes were observed.

 

The LD50 of the substance for male rats over the period of 14 days is greater than to 5020 mg/kg b.w. (3514 mg/kg b.w. based on the active ingredient).