1,4-bis(mesitylamino)anthraquinone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed GLP compliant OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,4-bis(mesitylamino)anthraquinone

EC Number:

204-155-7

EC Name:

1,4-bis(mesitylamino)anthraquinone

Cas Number:

116-75-6

Molecular formula:

C32H30N2O2

IUPAC Name:

1,4-bis(mesitylamino)anthraquinone

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A., Calco (Lecco), Italy
- Age at study initiation: 7-9 weeks
- Weight at study initiation: Approximately 200-240 g
- Housing: Individually caged (both during acclimatisation and study period)
- Diet (e.g. ad libitum): 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy); Ad libitum throughout the study
- Water (e.g. ad libitum): Drinking tap water supplied to each cage via a water bottle; Ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES:
From: 13 June 2012 – Allocation of the animals
To: 28 June 2012 – Necropsy of the animals

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

A volume of 1 mL of sterile water was added to weighed aliquot of the test item for each animal and mixed in order to achived a paste for the dosing procedure

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surfaces of the trunk of the animals
- % coverage: approximately 10% of body surface
- Type of wrap if used: A strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Aliquots were weighed according to the body weight of each animal measured prior to dosing
- For solids, paste formed: yes

Duration of exposure:

Single treatment

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days after dosing
- Frequency of observations and weighing:
Mortality and morbidity twice daily
Weighed on allocation, Days 1, 8 and 15 of the study period
Clinical signs on the day of dosing: At dosing, approximately 1, 2 and 4 hours after dosing, daily thereafter (14 days).
- Necropsy of performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality at 2000 mg/kg bw, the highest dose tested

Mortality:

No mortality occurred in male or female animals following treatment.

Clinical signs:

other: Clinical signs recorded during the observation period were limited to the treatment site (dorsum), both in male and female animals, in which slight/marked blue coloration was generally observed during the entire period of the study. In addition, blue stai

Gross pathology:

No internal abnormalities were found at necropsy examination performed on all animals at termination of the study.
At the external examination, all animals showed blue staining at the treated site (dorsum) and on the tail surface.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results obtained indicate that the test item has no systemic toxic effect in the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg bw. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg bw.

Executive summary:

The acute toxicity of the test item was investigated following dermal administration of a single dose to the rat.

A single dose of 2000 mg/kg bw moistened with water was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days all animals were killed and subjected to necropsy examination.

No mortality occurred following treatment in male or female animals during the observation period.

Clinical signs recorded during the observation period were limited to blue coloration of the treated site and on the tail surface during the entire period of the study. This blue coloration was attributed to the properties of the test item (blue). Scab on the dorsum was observed in one female only from Day 7 to Day 11. This sign was considered incidental and not related to the tolerability of the test item.

The body weight changes observed during the study were within the expected range for this species and age of animals.

No internal abnormalities were found at necropsy carried out in the animals at termination of the study. External examination revealed blue staining at the treated site (dorsum) and on the tail surface in all animals.

These results indicate that the test item has no systemic toxic effect in the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg bw. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg bw.