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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-12-21 - 2011-01-08 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study has been conducted according to the standard guideline(s) with (minor) deviations and its results are reliable, relevant and adequate for risk assessment and classification. This study has been initiated (in year 2010) for other purposes than to support a registration according to Regulation (EC) No 1907/2006 (REACH). It has not been carried out in compliance with the principles of good laboratory practice (GLP), which is, according to REACH Article 13 (4), required for toxicological tests. The study has been conducted according to the standard guideline(s) with some (minor) deviations. It was conducted in a facility operating to GLP within the UK national GLP monitoring programme, but the study report has not been audited by the QA Unit. No formal claim of GLP compliance is made for this study. However it has been declared by the study director that the report is an accurate record of the study and its outcome. The original data are retained in the archives of the test facility. The analytical characterisation of the test material has been performed according to GLP. After assessing all information on this study, the registrant has concluded that the following conditions are met: (1) adequacy for the purpose of classification and labelling and/or risk assessment; (2) adequate and reliable coverage of the key parameters foreseen to be investigated in the corresponding test methods referred to in Article 13(3); (3) exposure duration comparable to or longer than the corresponding test methods referred to in Article 13(3) if exposure duration is a relevant parameter; and (4) adequate and reliable documentation of the study is provided. Thus, according to REACH Annex XI, 1.1 ("Testing does not appear scientifically necessary - Use of existing data"), these existing data are considered to be acceptable for fulfilling the information requirements of this endpoint. As a consequence, the overall reliability rating (according to Klimisch et al.) is considered to be between "reliable with restrictions" and "not reliable", but closer to "reliable with restrictions". Thus a Klimisch rating of 2 (reliable with restrictions) has been assigned.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

minor deviations (e.g. no information is given on age of each animal at start of study, individual animal weights at start and conclusion of test, source of animals, housing conditions, diet, description of method used to score irritation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

minor deviations (e.g. no information is given on age of each animal at start of study, individual animal weights at start and conclusion of test, source of animals, housing conditions, diet, description of method used to score irritation)

Principles of method if other than guideline:

The study was performed to assess the irritation of the test item to the eye of the New Zealand White rabbit, according to a general study plan of the test facility. The method followed OECD Guidelines for Testing of Chemicals (24 April 2002) No. 405 “Acute Eye Irritation/Corrosion” and Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008.

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 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

single application of 0.1 ml (approximately 78 mg)

Duration of treatment / exposure:

single application

Observation period (in vivo):

1, 24, 48 and 72 hours after administration

Number of animals or in vitro replicates:

3 (males)

Details on study design:

A single application of 0.1 ml (approximately 78 mg) of the test item was administered to the non irrigated eye of three rabbits. Ocular reactions were recorded 1, 24, 48 and 72 hours after administration.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Results 2

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no corneal opacity noted during the course of the study

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect on the iris was noted during the course of the study

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

mean cornea scores (following grading at 24, 48 and 72 hours):
0, 0 and 0 for animal #1, animal #2 and animal #3, respectively

mean iris scores (following grading at 24, 48 and 72 hours):
0, 0 and 0 for animal #1, animal #2 and animal #3, respectively

mean conjunctivae (redness) scores (following grading at 24, 48 and 72 hours):
0.67, 0.67 and 0.33 for animal #1, animal #2 and animal #3, respectively

mean chemosis scores (following grading at 24, 48 and 72 hours):
0.33, 0 and 0 for animal #1, animal #2 and animal #3, respectively


for details see Table 1 under "Any other information on results incl. tables".

Any other information on results incl. tables

Individual reactions are given in Table 1. The test item produced moderate conjunctival irritation. One treated eye appeared normal at the 48-Hour observation and two treated eyes appeared normal at the 72-Hour observation.

Maximum Group Mean Score: 9.3

Classification: mild irritant (class 4 on a 1-8 scale)

For "Draize Scale for Scoring Ocular Irritation" and "Modified Kay and Calandra Interpretation of Eye Irritation Test" see the attachment of this endpoint study record.

Table 1: Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	69852 Male				69871 Male				69873 Male
	IPR = 2				IPR = 2				IPR = 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	1	0	1	1	1	0	2	1	0	0
B = Chemosis	2	1	0	0	1	0	0	0	1	0	0	0
C = Discharge	2	1	0	0	1	0	0	0	2	0	0	0
Score (A + B + C) x 2	12	6	2	0	6	2	2	0	10	2	0	0
Total Score	12	6	2	0	6	2	2	0	10	2	0	0

IPR = Initial pain reaction

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU: Regulation (EC) 1272/2008

Conclusions:

The study has been conducted according to the standard guideline(s) with (minor) deviations and its results are reliable, relevant and adequate for risk assessment and classification.

This study has been initiated (in year 2010) for other purposes than to support a registration according to Regulation (EC) No 1907/2006 (REACH). It has not been carried out in compliance with the principles of good laboratory practice (GLP), which is, according to REACH Article 13 (4), required for toxicological tests. The study has been conducted according to the standard guideline(s) with some (minor) deviations. It was conducted in a facility operating to GLP within the UK national GLP monitoring programme, but the study report has not been audited by the QA Unit. No formal claim of GLP compliance is made for this study. However it has been declared by the study director that the report is an accurate record of the study and its outcome. The original data are retained in the archives of the test facility. The analytical characterisation of the test material has been performed according to GLP.
After assessing all information on this study, the registrant has concluded that the following conditions are met:
(1) adequacy for the purpose of classification and labelling and/or risk assessment;
(2) adequate and reliable coverage of the key parameters foreseen to be investigated in the corresponding test methods referred to in Article 13(3);
(3) exposure duration comparable to or longer than the corresponding test methods referred to in Article 13(3) if exposure duration is a relevant parameter; and
(4) adequate and reliable documentation of the study is provided.
Thus, according to REACH Annex XI, 1.1 ("Testing does not appear scientifically necessary - Use of existing data"), these existing data are considered to be acceptable for fulfilling the information requirements of this endpoint. As a consequence, the overall reliability rating (according to Klimisch et al.) is considered to be between "reliable with restrictions" and "not reliable", but closer to "reliable with restrictions". Thus a Klimisch rating of 2 (reliable with restrictions) has been assigned.

Executive summary:

An in vivo study for eye irritation (OECD 405, rabbit) has been conducted. Based on its results, the test item is a mild irritant (class 4 on a 1-8 scale) according to Draize Scale for Scoring Ocular Irritation and Modified Kay and Calandra Interpretation of Eye Irritation Test.