Reaction mass of aluminium tris(5,7,12,14-tetrahydro-7,14-dioxoquino[2,3-b]acridine-2-sulphonate) and 5,12-dihydro-quino[2,3-b]acridine-7,14-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

according to GLP and OECD

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium tris(5,7,12,14-tetrahydro-7,14-dioxoquino[2,3-b]acridine-2-sulphonate)

EC Number:

278-207-2

EC Name:

Aluminium tris(5,7,12,14-tetrahydro-7,14-dioxoquino[2,3-b]acridine-2-sulphonate)

Cas Number:

75431-69-5

Molecular formula:

C20H12N2O5S.1/3Al

IUPAC Name:

aluminum tris(7,14-dioxo-5,7,12,14-tetrahydroquino[2,3-b]acridine-2-sulfonate)

Constituent 2

Reference substance name:

5,12-dihydroquino[2,3-b]acridine-7,14-dione

EC Number:

213-879-2

EC Name:

5,12-dihydroquino[2,3-b]acridine-7,14-dione

Cas Number:

1047-16-1

Molecular formula:

C20H12N2O2

IUPAC Name:

5,12-dihydroquino[2,3-b]acridine-7,14-dione

Constituent 3

Reference substance name:

Dialuminium tris(5,7,12,14-tetrahydro-7,14-dioxoquino[2,3-b]acridine-2,9-disulphonate)

EC Number:

243-319-2

EC Name:

Dialuminium tris(5,7,12,14-tetrahydro-7,14-dioxoquino[2,3-b]acridine-2,9-disulphonate)

Cas Number:

19795-24-5

Molecular formula:

C20H12N2O8S2.2/3Al

IUPAC Name:

dialuminium tris(5,7,12,14-tetrahydro-7,14-dioxoquino[2,3-b]acridine-2,9-disulphonate)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: appr. 10 weeks
- Weight at study initiation: 165 - 182 g (mean 179.7)
- Housing: single housing, Makrolon Cage, Type III
- Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH, 59494 Soest, Germany
- Enrichment: Wooden Gnawing blocks (Type NGM E-022); ABEDD LAb & VET Service GmbH, 1160 Vienna, Austria
- Diet: VRF1 (P), SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least five days
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was still available ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): appr. 10
- Photoperiod (hrs dark / hrs light): 12/12


Further Animal Information
Female Wistar (Crl:WI (Han) SPF) strain rats. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were appr. 10 weeks of age. The body weight variation did not exceed ± 20% of the mean body weight of any previously dosed animals.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Ph. Eur.

Details on oral exposure:

All animals were dosed once only by gavage

VEHICLE
- Concentration in vehicle: 40 % (w/v), suspension
- Amount of vehicle (if gavage): 5.00 mL/Kg bw

The homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 animals per dose, 2 dose groups

Control animals:

no

Details on study design:

Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.

All animals were dosed once only by gavage. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.

The animals were observed for deaths or overt signs of toxicity several times on the day of administration and at least once during each workday thereafter.
Individual body weights were recorded prior to dosing and 7 and 14 days after treatment or at death.
At the end of the observation period the surviving animals were killed by CO2 inhalation. All animals were subjected to gross pathological examination.

Data Evaluation
Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioral and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects.

Statistics:

None recorded

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% CL not reported

Mortality:

no mortality occurred in both 2000 mg/kg bw test groups.

Clinical signs:

other: clinical signs in the first 2000 mg/kg bw test group revealed in all animals impaired general state and piloerection from hour 2 until study day 1 after administration. clinical signs in the second 2000 mg/kg bw test group revealed in all animals impaired

Gross pathology:

there were no macroscopic findings in the surviving animals sacrificed at the end of the observation period (6 females).

Other findings:

None

Any other information on results incl. tables

    Individual Body Weights and Body Weight Changes

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight Gain (g) During Week
		0	7	14	1	2
2000	R 321 Female	165	186	190	26	4
	R 322 Female	167	194	202	27	8
	R 323 Female	166	189	199	23	10
	R 333 Female	176	197	206	21	9
	R 334 Female	181	196	205	15	9
	R 335 Female	182	204	214	22	10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Regulation (EC) 1272/2008

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was greater than 2000 mg/kg body weight. Therefore, the substance has not to be classified according to Regulation (EC) 1272/2008

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg body weight. This was followed by a further group of three fasted females at the same dose level. 

The test item was administered orally as a suspension in corn oil. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality.  no mortality occurred in both 2000 mg/kg bw test groups. 

Clinical Observations.  clinical signs revealed in all animals impaired general state and piloerection from hour 1 until study day 1 after administration. There were no signs of systemic toxicity noted in all animals. Red colored staining of the feces was noted in the cages of all animals.

Body Weight. With the exception of 1 animal expected gains in body weight wer noted.

Necropsy.  there were no macroscopic findings in the surviving animals sacrificed at the end of the observation period.

Conclusion

The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat is greater than 2000 mg/kg body weight. Therefore, the substance has not to be classified according to Regulation (EC) 1272/2008.