Sodium D-glycero-D-gulo-heptonate

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 18 February 2013 and 28 February 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 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 relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

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:

Sodium D-glycero-D-gulo-heptonate

EC Number:

235-849-8

EC Name:

Sodium D-glycero-D-gulo-heptonate

Cas Number:

13007-85-7

Molecular formula:

C7H14O8.Na

IUPAC Name:

sodium 2,3,4,5,6,7-hexahydroxyheptanoate (non-preferred name)

Test material form:

solid: crystalline

Details on test material:

Sponsor's identification : Sodium D-glycero-D-gulo-heptonate
Description : off white crystalline solid
Batch number : 921126700
Purity : 99%
Date received : 09 October 2012
Expiry date : 01 October 2015
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:

TEST ANIMALS
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.36 to 2.57 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 (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., 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.

ENVIRONMENTAL CONDITIONS
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 (volume or weight with unit): 0.1 ml of the test item, which was found to weigh approximately 70 mg (as measured by gently compacting the required volume into an adapted syringe).
- Concentration (if solution): 10% w/w aqueous preparation

Duration of treatment / exposure:

A volume of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

Three

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the numerical evaluation, (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).
Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

72974 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects noted.

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

73005 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects noted.

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

73004 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects noted.

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Remarks:

72974 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Remarks:

73005 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Remarks:

73004 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

72974 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

73005 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Effects noted at 1 hour.

Results 9

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

73004 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Effects noted at 1 hour.

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

72974 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Effects noted at 1 hour.

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

73005 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Effects noted a 1 hour

Results 12

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

73004 (Male)

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Effects noted at 1 hour

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 (please see "Any other information on results" below).
No corneal effects were noted during the study.
Iridial inflammation was noted in all treated eyes one hour after treatment.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Minimal conjunctival irritation was noted in all treated eyes at the 24 Hour observation and in two treated eyes at the 48 Hour observation.
One treated eye appeared normal at the 48 Hour observation and two treated eyes appeared normal at the 72 Hour observation.

Other effects:

Bodyweight
One animal showed bodyweight loss and two animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table1              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	72974Male				73005Male				73004Male
	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	1	0	0	0	1	0	0	0	1	0	0	0
Score (D x 5)	5	0	0	0	5	0	0	0	5	0	0	0
CONJUNCTIVAE
A = Redness	2	1	1	0	2	1	0	0	2	1	1	0
B = Chemosis	1	1	0	0	1	0	0	0	2	0	0	0
C = Discharge	1	0	0	0	2	0	0	0	1	0	0	0
Score (A + B + C) x 2	8	4	2	0	10	2	0	0	10	2	2	0
Total Score	13	4	2	0	15	2	0	0	15	2	2	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
72974Male	13	4	2	0
73005Male	15	2	0	0
73004Male	15	2	2	0
Group Total	43	8	4	0
Group Mean Score	14.3	2.7	1.3	0.0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 14.3 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.
The test item does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed tobe compatible with thefollowing:

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

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

Result. A single application of the test item to the non-irrigated eye of three rabbits produced iridial inflammation and moderate conjunctival irritation. One treated eye appeared normal at the 48‑Hour observation and two treated eyes appeared normal at the 72‑Hour observation.

Conclusion. The test item produced a maximum group mean score of 14.3 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.

The test item does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.