Decahydrospiro[furan-2(3H),5'-[4,7]methano[5H]indene]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 15 May 2003 and 11 June 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Information used for read across to Vigoflor.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Results derived from a valid read across, with adequate and reliable documentation / justification.

Justification for type of information:

The full read across justification is presented in the Endpoint summary and the accompanying file is also attached there.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: Read across information

Remarks on result:

other: Based on acute oral toxicity of Amber Xtreme and Cedramber (LD50 > 2500 mg/kg bw and LD50 > 5000 mg/kg bw, respectively) using conversion.

Interpretation of results:

other: Not classified, criteria not met

Remarks:

according to EU CLP 1272/2008 and its amendments

Conclusions:

For Vigoflor for acute oral toxicity LD50 >2000 mg/kg bw has been derived.

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

1

Reference substance name:

-

EC Number:

449-360-4

EC Name:

-

Cas Number:

476332-65-7

Molecular formula:

C18H32O

IUPAC Name:

Decahydro-2,2,6,6,7,8,8,heptamethyl-2H-Indeno[4,5-b] furan

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: bodyweights fell within an interval of ± 20% of the mean initial bodyweight of the first treated group
- Fasting period before study: overnight fast and for approximately three to four hours after dosing
- Housing: groups of three in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs continuous light (06:00 to 18:00) and 12 hrs darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.15 ml/kg

DOSAGE PREPARATION (if unusual): For the purpose of the study the test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In absence of data suggesting test material is toxic, 2000 mg/kg was chosen as the starting dose.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 (female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: 1/2, 1, 2, 4 hours after dosing and subsequently once daily for 14 days. Weighing: prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight. gross pathalogical examination.

Statistics:

None recorded.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Confidence intervals are not applicable in view of the absence of effects

Mortality:

There were no deaths.

Clinical signs:

There were no signs of systemic toxicity.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 1          Mortality

Dose Level mg/kg	Sex	Number of Animals Treated	Deaths During Day of Dosing (Hour)				Deaths During Period After Dosing (Days)								Deaths
			½	1	2	4	1	2	3	4	5	6	7	8-14
2000	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

Table 2          Individual Clinical Observations

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 3          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	223	248	273	25	25
	1-1 Female	222	263	283	41	20
	1-2 Female	242	275	298	33	23
	2-0 Female	213	258	278	45	20
	2-1 Female	214	258	283	44	25
	2-2 Female	236	259	291	23	32

Table 4          Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Macroscopic Observations
2000	1-0 Female	No abnormalities detected
	1-1 Female	No abnormalities detected
	1-2 Female	No abnormalities detected
	2-0 Female	No abnormalities detected
	2-1 Female	No abnormalities detected
	2-2 Female	No abnormalities detected

 

Applicant's summary and conclusion

Interpretation of results:

other: Not classified, criteria not met

Remarks:

according to EU CLP 1272/2008 and its amendments

Conclusions:

In an acute toxicity study performed according to the acute toxic class method (OECD423) and under GLP conditions, 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.

Executive summary:

In an acute oral toxicity study which was performed in accordance with the Acute Toxic Class method (OECD423) and under GLP conditions, a group of three fasted female Sprague-Dawley CD strain rats 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 undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No mortality was observed. All animals showed expected bodyweight gains over the study period. There were no signs of systemic toxicity and 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 estimated as being greater than 2500 mg/kg bodyweight, based on Annex 2d of OECD 423.