Overbased reaction products of distilled tall oil and magnesium hydroxide’

Eye irritation

Administrative data

Endpoint:

eye irritation, other

Remarks:

In vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 05 May 2010 and 26 May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in Section 13

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

The study was performed between 05 May 2010 and 26 May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: See ''Remark''

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in Section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

A volume of 0.1 ml of the test material, which was found to weigh approximately 79 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye

Duration of treatment / exposure:

Up to 1 hour

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 69182 Male

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: highest score observed at 1 hour timepoint

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 69190 Male

Time point:

other: 24, 48 and 72 hours, 7 and 14 days

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: highest score observed at 1 and 24 hour timepoints

Irritation parameter:

chemosis score

Basis:

animal: 69182 Male

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: highest score observed at 1 hour timepoint

Irritation parameter:

chemosis score

Basis:

animal: 66173 Male

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: highest score observed at 1 and 24 hour timepoints

Irritation parameter:

cornea opacity score

Basis:

animal: 69182 Male

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect noted

Irritation parameter:

cornea opacity score

Basis:

animal: 69190 Male

Time point:

other: 24, 48 and 72 hours, 7 and 14 days

Score:

0

Max. score:

4

Reversibility:

other: No effect noted

Irritation parameter:

iris score

Basis:

animal: 69182 Male

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: No effect noted

Irritation parameter:

iris score

Basis:

animal: 69190 Male

Time point:

other: 24, 48 and 72 hours, 7 and 14 days

Score:

0

Max. score:

2

Reversibility:

other: No effect noted

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 in any other information on results section.
No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Moderate conjun ctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in the other tr eated eye at the 24-Hour observation. Minimal conjunctival irritation was noted in two treated eyes at the 48-Hour observation and in one treated eye at the 72-Hour and 7-Day observations. One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 14 Day observation.

Interpretation of results:

other: modified Kay and Calandra classification system

Conclusions:

The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following: OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002) Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

Result. 

A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 14 Day observation.

Conclusion. 

The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids C18-(unsaturated) lithium salts

EC Number:

700-426-3

Cas Number:

502962-81-4

Molecular formula:

Since this is a complex mixture of constituents no single formula can be assigned

IUPAC Name:

Fatty acids C18-(unsaturated) lithium salts

Details on test material:

Sponsor's identification: Fatty acids C18-(unsaturated) lithium salts
Description : off white solid
Batch number : SF 173
Date received : 21 January 2010
Expiry date : 21 January 2012
Storage conditions: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Two New Zealand White rabbits were supplied by Harlan Laboratories UK Limited, Hillcrest, Belton, Loughborough, UK. At the start of the study the animals weighed 2.21 or 2.42 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
A volume of 0.1 ml of the test material, which was found to weigh approximately 79 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye

Duration of treatment / exposure:

Up to 1 hour

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not applicable

The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:
Score for conjunctivae = (A + B + C) x 2
Score for iris = D x 5
Score for cornea = (E x F) x 5
Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C (1962), J. Soc. Cosmet. Chem. 13, 281 289 (see Appendix 3) was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.
If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 69182 Male

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: highest score observed at 1 hour timepoint

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 69190 Male

Time point:

other: 24, 48 and 72 hours, 7 and 14 days

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: highest score observed at 1 and 24 hour timepoints

Results 3

Irritation parameter:

chemosis score

Basis:

animal: 69182 Male

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: highest score observed at 1 hour timepoint

Results 4

Irritation parameter:

chemosis score

Basis:

animal: 66173 Male

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: highest score observed at 1 and 24 hour timepoints

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal: 69182 Male

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effect noted

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal: 69190 Male

Time point:

other: 24, 48 and 72 hours, 7 and 14 days

Score:

0

Max. score:

4

Reversibility:

other: No effect noted

Results 7

Irritation parameter:

iris score

Basis:

animal: 69182 Male

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: no effect noted

Results 8

Irritation parameter:

iris score

Basis:

animal: 69190 Male

Time point:

other: 24, 48 and 72 hours, 7 and 14 days

Score:

0

Max. score:

2

Reversibility:

other: no effect noted

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 in any other information on results section.
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in the other treated eye at the 24-Hour observation. Minimal conjunctival irritation was noted in two treated eyes at the 48-Hour observation and in one treated eye at the 72-Hour and 7-Day observations.
One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 14 Day observation.

Any other information on results incl. tables

Table 1              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	69182 Male				69190 Male
	IPR= 3				IPR = 0+
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	14 Days
CORNEA
E = Degree of Opacity	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
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	1	0	2	2	1	1	1	0
B = Chemosis	2	1	0	0	2	2	1	1	1	0
C = Discharge	2	1	0	0	2	2	1	1	1	0
Score (A + B + C) x 2	12	6	2	0	12	12	6	6	6	0
Total Score	12	6	2	0	12	12	6	6	6	0

IPR = Initial pain reaction

+ = One drop of local anaesthetic instilled into both eyes 1 to 2 minutes before treatment

Table 2              Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	14 Days
69182 Male	12	6	2	0	-	-
69190 Male	12	12	6	6	6	0
Group Total	24	18	8	6	6	0
Group Mean Score	12.0	9.0	4.0	3.0	3.0	0.0

- = Observation not required - considered to be zero for calculation of Group Mean Score

Applicant's summary and conclusion

Interpretation of results:

other:

Remarks:

Criteria used for interpretation of results: other: modified Kay and Calandra classification system

Conclusions:

The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye
according to a modified Kay and Calandra classification system.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

Result. A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 14 Day observation.

Conclusion. The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.