Sodium 5-oxo-DL-prolinate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 April 2012 to 29 April 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available on the read across substance, sodium 5-oxo-L-prolinate, which is a structural analogue of the registered substance. This is a non GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data. The study followed a methodology similar to OECD 406. The report was redrafted several years after the study period. Read-across is considered to be suitable based on the structural similarities between the read across substance (sodium 5-oxo-L-prolinate) and the substance to be registered (sodium 5-oxo-DL-prolinate).

Justification for type of information:

A valid study is available on the read across substance, sodium 5-oxo-L-prolinate, which is a structural analogue of the registered substance. This is a non GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data. The study followed a methodology similar to OECD 406. The report was redrafted several years after the study period. Read-across is considered to be suitable based on the structural similarities between the read across substance (sodium 5-oxo-L-prolinate) and the substance to be registered (sodium 5-oxo-DL-prolinate).

Cross-reference

Reason / purpose for cross-reference:

other: Target substance

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read across material

Justification for type of information:

A valid study is available on the read across substance, sodium 5-oxo-L-prolinate, which is a structural analogue of the registered substance. This is a non GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data. The study followed a methodology similar to OECD 406. The report was redrafted several years after the study period. Read-across is considered to be suitable based on the structural similarities between the read across substance (sodium 5-oxo-L-prolinate) and the substance to be registered (sodium 5-oxo-DL-prolinate).

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(the eyes of the test animals were washed 1 hour after administration of the test material).

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

(the eyes of the test animals were washed 1 hour after administration of the test material).

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

(the eyes of the test animals were washed 1 hour after administration of the test material).

GLP compliance:

no

Remarks:

The report was redrafted several years after the study period. At the time of the study period GLP compliance was not a requirement.

Test material

Test material information

Constituent 1

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Molecular formula:

C3H8O

IUPAC Name:

Propan-2-ol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: White to pale yellow powder.
- Storage condition of test material: Controlled room temperature (15-25 °C, below 70 RH %), protected from humidity.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 14 weeks old (adults).
- Weight at study initiation: Males ranged from 3251 to 3518 g.
- Housing: Individually in open wire cages.
- Diet: rabbit diet, ad libitum.
- Water: Municipal tap water, ad libitum.
- Acclimation period: 29 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 to 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light per day between 06:00 and 18:00 hours.

IN-LIFE DATES: From: 26 April To: 29 April

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g.

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

72 hours.

Number of animals or in vitro replicates:

Three

Details on study design:

DOSING
- Procedure: An initial test was performed using one animal to assess the initial pain reaction. After consideration of the ocular responses produced in the first animal, one hour after the treatment of the first animal, two additional animals were treated.
- Administration: The test material was instilled into the conjunctival sac of the left eye. The eyelids were held closed for a few seconds to prevent the loss of the test item.

SCORING SYSTEM
- Initial pain reaction: Immediately after the administration of the test material, an assessment of the initial pain reaction was made according to the six point scale shown in Table 1.
- Ocular response: The eyes were examined at 1, 24, 48 and 72 hours after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. The eye irritation scores were evaluated according to the scoring system by Draize (1977) shown in Table 2.

OTHER OBSERVATIONS:
- Clinical: Any clinical signs of toxicity or signs of ill-health during the study were recorded.
- Bodyweight: Individual body weight was recorded at the beginning and end of the experiment.
- Necropsy: Performed at termination of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

3

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: Mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Initial Pain Reaction (IPR): A score of 2 was observed in all animals.
- One hour after the application: Conjunctival redness (score 1 or 2) and discharge (score 1 or 2) were seen in all rabbits. One animal showed conjuctival chemosis (score 1).
- At 24 hours after treatment: Conjunctival redness (score 1) was seen in one rabbit.
- At 48 and 72 hours after treatment: No signs of eye irritation were observed.
- Reversibility: As all signs of eye irritation had fully reversed the study was terminated after a period of 72 hours observation.

Other effects:

- Mortality: None observed during the study.
- Bodyweight: The body weight and body weight change were considered to be normal with no indication of a treatment related effect. Bodyweights ranged from 3420 to 3553 g at termination representing a weight gain of between 35 and 169 g.
- Clinical: There were no clinical signs observed that could be related to treatment.

Any other information on results incl. tables

Table 3: Individual Scores for Ocular Irritation at 1 Hour

Animal No.	Score of Irritation								IPR
	Conjunctivae			Opacity of Cornea		Iris	Control Eye	Other Signs
	R	CH	D	OD	OE	R
1	2	1	1	0	0	0	0	-	2
2	1	0	1	0	0	0	0	-	2
3	2	0	2	0	0	0	0	-	2

 

Table 4: Individual Scores for Ocular Irritation at 24 Hour

Animal No.	Score of Irritation
	Conjunctivae			Opacity of Cornea		Iris	Control Eye	Other Signs
	R	CH	D	OD	OE	R
1	0	0	0	0	0	0	0	-
2	0	0	0	0	0	0	0	-
3	1	0	0	0	0	0	0	-

 

Table 5: Individual Scores for Ocular Irritation at 48 Hour

Animal No.	Score of Irritation
	Conjunctivae			Opacity of Cornea		Iris	Control Eye	Other Signs
	R	CH	D	OD	OE	R
1	0	0	0	0	0	0	0	-
2	0	0	0	0	0	0	0	-
3	0	0	0	0	0	0	0	-

 

Table 6: Individual Scores for Ocular Irritation at 72 Hour

Animal No.	Score of Irritation
	Conjunctivae			Opacity of Cornea		Iris	Control Eye	Other Signs
	R	CH	D	OD	OE	R
1	0	0	0	0	0	0	0	-
2	0	0	0	0	0	0	0	-
3	0	0	0	0	0	0	0	-

 

R = redness, CH = chemosis; D = discharge; OD = opacity degree of density; OE = extent of opaque area; IPR = initial pain reaction.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the test material was determined to be non-irritating. Incidences of conjunctival redness and discharge were observed in all three animals one hour after administration, and one animal also showed evidence of chemosis. All ocular reactions were fully reversed by 48 hours post exposure. These reactions were slight and below the limit of classification.

Executive summary:

The potential for the test material to cause eye irritation was assessed in an in vivo irritation study in rabbits. The study was performed under GLP conditions in line with standardised guidelines OECD 405, EU Method B.5 and EPA OPPTS 870.2400. The test material was administered to three male New Zealand white rabbits, in a single 1 hour application. Rabbits were assessed over 72 hours for signs of eye irritation, clinical sign of toxicity, mortality and bodyweight gain. Application of the test material to the rabbit’s eye caused evidence of conjunctival redness and discharge in all three animals, one hour after administration. One animal also showed evidenece of chemosis at one hour. These signs of irritation were fully reversed within 48 hours, and subsequently the study was terminated after 72 hours. Under the conditions of the study, the test material was determined to be non-irritating.

This study was conducted on the the read across substance, sodium 5-oxo-L-prolinate.