1H-Inden-1-one, 2,3-dihydro-5,6-dimethoxy-3,3-dimethyl-2-(phenylmethylene)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 09, 2006 - June 28, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: 2004/73/EC B.1 tris (acute-toxic-class-method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2005-11-21

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

486-080-1

EC Name:

-

Cas Number:

924626-15-3

Molecular formula:

C20H20O3

IUPAC Name:

Reaction mass of (2E)-2-Benylidene-5,6-dimethoxy-3,3-dimethylindan-1-one and (2Z)-2-Benylidene-5,6-dimethoxy-3,3-dimethylindan-1-one

Details on test material:

Name: BIO 1031/1
Substance type: pure active substance
Physical state: solid
Storage condition of test material: ambient temp., dark, dry, in original container

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd. The rats were nulliparous and non-pregnant.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 208-224 g
- Fasting period before study: an overnight fast immediately before dosing
- Housing: The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London; ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: 15 per hour
- Photoperiod: 12 hours light/dark cycle

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. The volume administered to each rats was calculated according to the fasted body weight at the time of dosing. Treatment of animals were sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

Doses:

Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.

No. of animals per sex per dose:

2 x 3 rats per dosing group (2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes; At the end of the observation period the rats 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.

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.

Statistics:

not applicable

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Signs of toxicity related to dose levels: Hunched posture and pilo erection were observed after one hour at one animal in group two. Other signs of systemic toxicity noted during the study were hunched posture, lethargy, pilo-erection and decreased

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual clinical observations

Dose level (mg/kg)	Animal number and sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		0.5	1	2	4	1	2-14
2000	1-0 female	0	0	0	HLP Rd	HP Rd	0
	1-1 female	0	0	0	HLP Rd	HP Rd	0
	1-2 female	0	0	0	HLP Rd	HP Rd	0
	2-0 female	0	0	HP	HLP Rd	HP Rd	0
	2-1 female	0	0	0	HLP Rd	HP Rd	0
	2-2 female	0	0	0	HLP Rd	HLP Rd	0

H = hunched posture, L = lethargy, P = pilo-erection, Rd = decreased respiratory rate

Table 2: Individual bodyweights and weekly bodyweight changes

Dose level (mg/kg)	Animal number and sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
2000	1-0 female	208	237	261	29	24
	1-1 female	210	248	250	38	2
	1-2 female	209	239	251	30	12
	2-0 female	224	257	279	33	22
	2-1 female	214	235	270	21	35
	2-2 female	210	253	259	43	6

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Since no deaths occurred in any of the 6 animal tested at the highest dose of 2000 mg/kg bw, according to the guideline the substance belongs to the Category 5 (GHS) “unclassified” and the corresponding LD 50 > 5000 mg/kg bw.