Benzo[rst]phenanthro[10,1,2-cde]pentaphene-9,18-dione, reaction products with 1-chlorododecane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6-9-2014 to 7-18-2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed in accordance with GLP. The only exception is that GLP characterization of the test material was not carried out.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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:

Dinaphtho[1,2,3-cd:1',2',3'-lm]perylene-9,18-dione, dodecyl derivs.

EC Number:

270-145-4

EC Name:

Dinaphtho[1,2,3-cd:1',2',3'-lm]perylene-9,18-dione, dodecyl derivs.

Cas Number:

68411-75-6

Molecular formula:

Unspecified

IUPAC Name:

Dinaphtho[1,2,3-cd:1',2',3'-lm]perylene-9,18-dione, dodecyl derivs.

Test material form:

other: Red liquid

Details on test material:

- Name of test material (as cited in study report): C.I. Solvent Red 175
- Physical state: Liquid
- Lot/batch No.: ZA-4282014
- Storage condition of test material: As per the instruction received from the Sponsor on storage of the test item, the test item was stored in its original container as supplied by the Sponsor at ambient condition in the Test Item Control Office (TICO).
- Other: Analyzed Concentration (Sponsor): 100%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: Minimum: 166.4, Maximum: 187.4
- Fasting period before study: overnight fasting and three hours post-dosing
- Housing: Rats were housed three rats/cage in standard polypropylene solid bottom cages which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). These cages have stainless steel top grills with steam sterilized corn cob bedding material and facilities for pelleted feed and drinking water (polypropylene bottle fitted with sipper tube). Rack units were rotated once in a week.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 to 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23 °C
- Humidity (%): 65 to 67% relative humidity
- Air changes (per hr): 18 air changes/hour
- Photoperiod (hrs dark / hrs light): The photoperiod was 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h which was maintained through an automatic timer.

IN-LIFE DATES: From: June 12, 2014 To: July 4, 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: When the information suggests that mortality is unlikely at the highest dose level (2000 mg/kg body weight), then a limit test should be conducted. An initial dose of 2,000 mg/kg may be administered to three animals, in a step-wise method if necessary.

Dose Administration:
Individual dose volume was adjusted according to body weight, dose level and specific gravity of the test item. All rats were dosed by oral gavage (day 1) using a metal cannula attached to a BD 1 mL disposable syringe which was graduated up to 1 mL. Rats were fasted overnight prior to dosing until three hours post-dosing.

Limit Study:
Three female rats from set 1 were given a single dose of 2000 mg C.I. Solvent Red 175/kg body weight. As no mortality was observed up to approximately 48 hours at this dose level, another three female rats from set 2 were administered with the same dose of 2000 mg C.I. Solvent Red 175/kg body weight. As no mortality was observed at this dose level, further testing was not required.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed for signs of toxicity and mortality at ½, 1, 2, 3, 4 and 6 hours postadministration on the day of dosing. Subsequently, they were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. The clinical signs were recorded once a day. Individual body weights were recorded prior to dosing on day 1, and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: A gross pathological examination at necropsy consisting of an external examination and opening of abdominal and thoracic cavities was performed. The stomach of each rat was opened, the contents rinsed/removed, and the mucosal surface was examined for signs of irritation, erosions, ulcers or any other findings. Gross macroscopic changes, if any, were recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in any of the rats treated at the dose level of 2000 mg C.I. Solvent Red 175/kg body weight.

Clinical signs:

other: No sign of toxicity was observed in rats treated at the dose level of 2000 mg C.I. Solvent Red 175/kg body weight.

Gross pathology:

External examination of the terminally sacrificed rats did not reveal any pathological lesions in any of the treated animals. Visceral examination of rats sacrificed at termination did not reveal any pathological lesions in any of the treated animals.

Any other information on results incl. tables

TABLE 1: Test Sequence, Doses, Specific Gravity and Mortalities

Sex: Female

Rat No.	Dose (mg/kg body weight)	Dose Volume (mL)	Mortality after Dosing at
			½ - 6 h	24 h	48 h	72 h	5 – 8 Day	9 – 15 Day
1	2000	0.41	O	O	O	O	O	O
2	2000	0.40	O	O	O	O	O	O
3	2000	0.42	O	O	O	O	O	O
4	2000	0.45	O	O	O	O	O	O
5	2000	0.42	O	O	O	O	O	O
6	2000	0.43	O	O	O	O	O	O

Key: O = Survived

Note: The test substance was administered as received.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No mortality was observed in the treated rats. Rats treated with the C.I. Solvent Red 175 at 2000 mg/kg body weight showed no signs of toxicity. The acute oral LD50 of the C.I. Solvent Red 175 was estimated to be greater than 2000 mg/kg body weight in female Wistar rats.

Executive summary:

An acute oral toxicity study (Acute Toxic Class Method) was conducted using female Wistar rats given a single oral dose of C.I. Solvent Red 175 (undiluted, as received). A Limit Test was conducted with 2000 mg/kg body weight. The first set of three rats survived; hence an additional set of three female Wistar rats each received a single dose of 2000 mg/kg body weight according to the Acute Toxic Class Method. No mortality was observed in the treated rats. Rats treated with the C.I. Solvent Red 175 at 2000 mg/kg body weight showed no signs of toxicity. All animals were active and healthy and gained body weight during the course of the study.

External and visceral examination of terminally sacrificed rats did not reveal any pathological lesions in any of the treated animals. The acute oral LD50 of the C.I. Solvent Red 175 was estimated to be greater than 2000 mg/kg body weight in female Wistar rats.