1-Octadecanamine, reaction products with 1,1'-methylenebis[4-isocyanatobenzene]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 07 September 2009 and 17 September 2009.

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

PU Thickener

IUPAC Name:

PU Thickener

Test material form:

other: beige solid pieces

Details on test material:

Sponsor's identification: PU Thickener
Description : beige coloured solid
Batch number : VPSG011
Date received : 31 July 2009
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:

Animals and Animal Husbandry

Two New Zealand White rabbits were supplied by Harlan Laboratories U.K. Ltd, Hillcrest, Belton, Loughborough, UK. At the start of the study the animals weighed 2.34 or 2.63 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:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

TEST MATERIAL
Amount(s) applied:
A volume of 0.1 ml of the test material (weighing approximately 60 mg) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

Concentration: used as supplied

VEHICLE
Amount(s) applied:
Not applicable

Concentration:
Not applicable

Lot/batch no. :
Not applicable

Purity:
Not reported

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

Approximately 1 hour and 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

2 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, one additional animal was treated).

Details on study design:

SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix 2-see section any other information on materials, (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 68547 Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 68562 Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 3

Irritation parameter:

iris score

Basis:

animal: 68547 Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: no effects observed

Results 4

Irritation parameter:

iris score

Basis:

animal: 68562 Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: no effects observed

Results 5

Irritation parameter:

other: redness

Basis:

animal: 68547 Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: score observed at 1 hour

Results 6

Irritation parameter:

other: redness

Basis:

animal: 68562 Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: score observed at 1 hour

Results 7

Irritation parameter:

chemosis score

Basis:

animal: 68547 Male

Time point:

other: 1, 24, 48 and 72

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: score observed at 1 hour

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 68562Male

Time point:

other: 1, 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: score observed at 1 hour

Irritant / corrosive response data:

Ocular Reactions
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 (see section any other information on results)
No corneal or iridial effects were noted during the test.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation.
Both treated eyes appeared normal at the 48-hour observation.

Other effects:

Bodyweight
Individual bodyweights and bodyweight changes are given in Table 3 (see section any other information on results)
Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Interpretation of Results

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 ( Modified Kay and Calandra Interpretation of Eye Irritation Test 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.

Table 1              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	68547Male				68562Male
	IPR= 2				IPR = 2
Time After Treatment	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
F = Area of Cornea Involved	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	0	0	2	1	0	0
B = Chemosis	1	0	0	0	1	0	0	0
C = Discharge	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	8	2	0	0	8	2	0	0
Total Score	8	2	0	0	8	2	0	0

IPR= Initial pain reaction

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
68547Male	8	2	0	0
68562Male	8	2	0	0
Group Total	16	4	0	0
Group Mean Score	8.0	2.0	0.0	0.0

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
68547Male	2.63	2.70	0.07
68562Male	2.34	2.42	0.08

Applicant's summary and conclusion

Interpretation of results:

other: minimal irritant

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 8.0 and was classified as a minimal irritant (Class 3 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 Commission Regulation (EC) No. 440/2008

Result. 

A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 48 hour observation.

Conclusion. 

The test material produced a maximum group mean score of 8.0 and was classified as aminimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.