Reaction mass of (1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1S,4R,4aS,8S,8aR)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1R,4S,4aR,8S,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1S,4R,4aS,8R,8aR)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2010-12-21 - 2010-12-28 (experimental phase)

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study provides some useful information about the properties of the test item. However it has been conducted only at a screening level. No specific reference to a guideline is given in the study report. However it is assumed that the study design has been based on the main principles of a corresponding relevant guideline and that the study did not follow the corresponding guideline in detail. The level of information collected/reported is limited. In addition the study has not been performed according to GLP. As a consequence the reliability ("evaluating the inherent quality of a test report or publication relating to preferably standardized methodology and the way the experimental procedure and results are described to give evidence of the clarity and plausibility of the findings"), relevance ("covering the extent to which data and tests are appropriate for a particular hazard identification or risk characterization") and adequacy ("defining the usefulness of data for hazard/risk assessment purposes") of the data ("data quality") are considered as limited and an overall reliability rating of 3 (= not reliable, according to the scoring system of Klimisch et al.) has been assigned.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Single oral administration in the Wistair strain rat, according to a general study plan of the test facility.

GLP compliance:

no

Remarks:

However, the study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme. The analytical characterisation of the test material has been performed according to GLP.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1S,4R,4aS,8S,8aR)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1R,4S,4aR,8S,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1S,4R,4aS,8R,8aR)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

EC Number:

700-770-4

Molecular formula:

C12H14Cl2O2

IUPAC Name:

Reaction mass of (1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1S,4R,4aS,8S,8aR)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1R,4S,4aR,8S,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one and (1S,4R,4aS,8R,8aR)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test item was administered orally as a solution in 5% carboxymethyl cellulose

Doses:

300 mg/kg bodyweight (single dose tested)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

A group of three fasted female animals was treated with the test item at a dose level of 300 mg/kg bodyweight. Dosing was performed sequentially. The test item was administered orally as a solution in 5% carboxymethyl cellulose. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

There were no macroscopic findings reported.

Other findings:

Individual clinical observations and mortality data are given in Table 1.
There were no deaths. No signs of systemic toxicity were noted.
Individual bodyweights and bodyweight changes are given in Table 2 and individual necropsy findings are given in Table 3.
There were no macroscopic findings reported.

Any other information on results incl. tables

Table 1: Individual Clinical Observations and Mortality Data

		Effects Noted After Dosing (Hours)				Effects Noted During Period After dosing (Days)
Dose Level mg/kg	Animal Number and Sex	1/2	1	2	4	1	2	3	4	5	6	7
300	1-0 Female	0	0	0	0	0	0	0	0	0	0	0
300	1-1 Female	0	0	0	0	0	0	0	0	0	0	0
300	1-2 Female	0	0	0	0	0	0	0	0	0	0	0

0 = No signs of systemic toxicity

Table 2: Individual Bodyweights and Bodyweight Changes

		Bodyweight (g)			Bodyweight Gain (g)
Dose Level mg/kg	Animal Number and Sex	Day -1	Day 0 (Day of Dosing)	Day 7	Day -1 to Day 0	Day 0 to Day 7
300	1-0 Female	176	177	189	1	12
300	1-1 Female	202	204	222	2	18
300	1-2 Female	180	181	200	1	19

Table 3: Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 7	No abnormalities detected
300	1-1 Female	Killed Day 7	No abnormalities detected
300	1-2 Female	Killed Day 7	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

other: see Conclusions below

Conclusions:

This study provides some useful information about the properties of the test item. However it has been conducted only at a screening level. No specific reference to a guideline is given in the study report. However it is assumed that the study design has been based on the main principles of a corresponding relevant guideline and that the study did not follow the corresponding guideline in detail. The level of information collected/reported is limited. In addition the study has not been performed according to GLP.

As a consequence the reliability ("evaluating the inherent quality of a test report or publication relating to preferably standardized methodology and the way the experimental procedure and results are described to give evidence of the clarity and plausibility of the findings"), relevance ("covering the extent to which data and tests are appropriate for a particular hazard identification or risk characterization") and adequacy ("defining the usefulness of data for hazard/risk assessment purposes") of the data ("data quality") are considered as limited and an overall reliability rating of 3 (= not reliable, according to the scoring system of Klimisch et al.) has been assigned.

Executive summary:

According to the results of the screening level acute oral toxicity test (rat), the approx. LD50 is >300 mg/kg bw. No deaths were observed at 300 mg/kg bw (the single dose tested).