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Toxicological information

Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
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

Constituent 1
Chemical structure
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
Chemical structure
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
Chemical structure
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.