Indeno[4,5-d]-1,3-dioxin, 4,4a,5,6,7,8,9,9b-octahydro-7,7,8,9,9-pentamethyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 14 April 2003 and 06 May 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with OECD TG 423 and according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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:

-

EC Number:

446-220-4

EC Name:

-

Cas Number:

365411-50-3

Molecular formula:

C16 H26 O2

IUPAC Name:

7,7,8,9,9-pentamethyl-2H,4H,4aH,5H,6H,7H,8H,9H,9bH-indeno[4,5-d][1,3]dioxine

Test material form:

other: Solid block liquefied by heating

Details on test material:

Sponsor's identification: 2-EYED MUSK
Description: solid block
Date received: 05 February 2003
Storage conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Female Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non-pregnant. After an acclimatisation period of at least five 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 eight to twelve weeks of age. The bodyweights fell within an interval of ± 20 % of the mean initial bodyweight of the first treated group.

The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by International Product Supplies Limited, Wellingborough, Northants, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 female

Control animals:

no

Details on study design:

In the absence of data suggesting the test material was toxic, 2000 mg/kg was chosen as the starting dose.

Groups of fasted animals were treated as follows:

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/mL) (ml/kg) (female)
2000 200 10 3
2000 200 10 3

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

None recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

Evaluation of Data

Data evaluations included the relationship, if any, between the exposure of the animal to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made as shown in the schematic diagram in Appendix 1 (attachment 1).

The results were evaluated according to Commission Directive 2001/59/EC for classification and labelling of dangerous substances and preparations.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 2500 mg/kg bodyweight. Criteria used for interpretation of results: other: EU labelling regulations Commission Directive 2001/59/EC.

Conclusions:

The acute toxcity of the test material via the dermal route was assessed accpording to OECD Guideline 423. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated from the flow chart in Appendix 1 (attachment 1) as being greater than 2500 mg/kg bodyweight. As such, the test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

The acute oral toxicity of the test material was tested following a single oral administration in the Sprague-Dawley CD strain rat according to OECD TG 423 Acute Toxic Class Method. A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test material was administered orally as a solution in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. There were no signs of systemic toxicity. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.The acute oral median lethal dose (LD₅₀) of the test material in the female Sprague-Dawley CD strain rat was greater than 2500 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.