2,9-bis(p-methoxybenzyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,9-bis(p-methoxybenzyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

EC Number:

280-472-4

EC Name:

2,9-bis(p-methoxybenzyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

Cas Number:

83524-75-8

Molecular formula:

C40H26N2O6

IUPAC Name:

7,18-bis[(4-methoxyphenyl)methyl]-7,18-diazaheptacyclo[14.6.2.2²,⁵.0³,¹².0⁴,⁹.0¹³,²³.0²⁰,²⁴]hexacosa-1(23),2,4,9,11,13,15,20(24),21,25-decaene-6,8,17,19-tetrone

Details on test material:

Test materials used in this dossier are all considered to fall under the definition of nano-materials according to the European Commission Recommendation 2011/696/EU as the synthesis and manufacturing of this pigment always yields particulate material with a fine particle size distribution.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Age at study initiation: About 12 weeks
- Weight at study initiation: 209 g (males) and 187 g (females)
- Fasting period before study: 16 hours before administration
- Housing: Type DK-111 stainless steel wire mesh cages (supplied by Becker L Co., Castrop-Rauxel, FRG), 5 animals/cage
- Diet (e.g. ad libitum): Ssniff R; supplied by Ssniff, Versuchstierdiäten, D-4470 Soest, FRG
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Acclimatisation for at least one week in the animal care unit

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully airconditioned rooms
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%

Details on oral exposure:

- Concentration in vehicle: 25 % (w/v)
- Administration volume: 20 ml/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Cage side observations: recording of signs several times on the day of administration, at least once each workday. Check for moribund and dead animals twice each workday and once daily on weekends and public holidays.
- Body weights: beginning of the test, day 3, 7 and 13
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

None of the animals died during the observation period.

Clinical signs:

other: Blue faeces at day 1 and 2.

Gross pathology:

No abnormal findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for the tested substance is above the tested dose of 5000 mg/kg bw.

Executive summary:

In an oral toxicity study comparable to OECD guideline 401, five Wistar rats per sex were treated with the test article at a single dose of 5000 mg/kg bw by gavage followed by a 14-day observation period. None of the animals died during the exposure period. At day 1 and 2 of the observation period the feces were blue. The animals showed a normal body weight gain. No abnormal findings were observed at necropsy. Therefore, based on the results of this study, the LD50 was determined at greater than 5000 mg/kg body weight.