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: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2011-01-05 - 2011-01-13 (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 dermal administration in the Wistar 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:

male/female

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

A group of four animals (two males and two females) was given a single, 24-hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. 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:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Individual clinical observations and mortality data are given in Table 1. Individual dermal reactions are given in Table 2

Gross pathology:

Individual necropsy findings are given in Table 4

Other findings:

Individual clinical observations and mortality data are given in Table 1. Individual dermal reactions are given in Table 2.
There were no deaths. Red/brown staining around the snout was noted during the day of dosing. No other signs of systemic toxicity were noted. Very slight erythema and desquamation and/or small superficial scattered scabs were noted in the females. No signs of dermal irritation were noted in the males.
Individual bodyweights and weekly bodyweight changes are given in Table 3 and individual necropsy findings are given in Table 4.

Any other information on results incl. tables

Results:

Table 1: Individual Clinical Observations and Mortality Data

Effects Noted After Initiation of Exposure (Hours)

Effects Noted After Initiation of Exposure (Days)

Dose Level (mg/kg)

Animal Number and Sex

1/2

1

2

4

1

2

3

4

5

6

7

8

2000

1-0 Male

NAD

Ss

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

2000

1-1 Male

Ss

Ss

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

2000

2-0 Female

NAD

Ss

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

2000

2-1 Female

NAD

Ss

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD

NAD = No abnormalities detected

Ss = Red/brown staining around the snout

Table 2: Individual Dermal Reactions*

			Effects Noted After Initiation of Exposure (Days)
Dose Level mg/kg	Animal Number and Sex	Observation	1	2	3	4	5	6	7	8
2000	1-0 Male	Erythema	0	0	0	0	0	0	0	0
2000	1-0 Male	Oedema	0	0	0	0	0	0	0	0
2000	1-0 Male	Other	0	0	0	0	0	0	0	0
2000	1-1 Male	Erythema	0	0	0	0	0	0	0	0
2000	1-1 Male	Oedema	0	0	0	0	0	0	0	0
2000	1-1 Male	Other	0	0	0	0	0	0	0	0
2000	2-0 Female	Erythema	0	0	0	0	0	0	0	0
2000	2-0 Female	Oedema	0	0	0	0	0	0	0	0
2000	2-0 Female	Other	0	0	0	0	0	0	Ss	0
2000	2-1 Female	Erythema	0	1	1	1	1	1	0	0
2000	2-1 Female	Oedema	0	0	0	0	0	0	0	0
2000	2-1 Female	Other	0	0	0	D	D	Ss	0	0

0 = No reactions

* = Scoring performed according to Draize (see Appendix 1)

Ss = Small superficial scattered scabs

D = Desquamation

Table 3: Individual Bodyweights and Weekly Bodyweight Changes

		Bodyweight (g) at Day		Bodyweight Change (g)
Dose Level mg/kg	Animal Number and Sex	Day of Dosing	Day 8	Day 0 to Day 8
2000	1-0 Male	294	295	1
2000	1-1 Male	296	302	6
2000	2-0 Female	225	216	-9
2000	2-1 Female	240	238	-2

Table 4: Individual Necropsy Findings

Dose Levelmg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Male	Killed Day 8	No abnormalities detected
2000	1-1 Male	Killed Day 8	No abnormalities detected
2000	2-0 Female	Killed Day 8	No abnormalities detected
2000	2-1 Female	Killed Day 8	No abnormalities detected

For "Scale According to Draize", see the Appendix (attachment to this endpoint study record).

 

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 dermal toxicity test (rat), the approx. LD50 is >2000 mg/kg bw. No deaths were observed at 2000 mg/kg bw (the single dose tested).