2-methylpropyl-(R)-2-hydroxypropanoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

1994-06-14 to 1994-09-22

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. 2-ethylhexyl lactate used as read-across partner.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

186817-80-1

Cas Number:

186817-80-1

IUPAC Name:

186817-80-1

Constituent 2

Reference substance name:

2-ethylhexyl lactate

EC Number:

228-503-2

EC Name:

2-ethylhexyl lactate

Cas Number:

6283-86-9

Molecular formula:

C11H22O3

IUPAC Name:

2-ethylhexyl 2-hydroxypropanoate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 2-ethylhexyl-lactate
- Chemical name: (S)-2-hydroxypropanoic acid (R,S)-2-ethylhexylester
- Physical state: clear, colourless liquid
- Analytical purity: min. 97 %
- Storage condition of test material: Ambient

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Instituut BV, Someren, the Netherlands
- Age at study initiation: young adult, sex not determined
- Date of arrival: 1994-05-18 (animal number 29 and 30) or 1994-06-01 (animal number 37)
- Date of dosing: 1994-06-14 (animal number 37) and 1994-06-15 (animal number 29 and 30)
- Weight at study initiation: 2250-2940 g
- Housing: individually in a stainless steel cage, fitted with a perforated floor
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 and 27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 42-82.5
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 1994-06-01 to 1994-07-08

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated, serving as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): min. 97 %

Duration of treatment / exposure:

An amount of 0.1 mL of the test substance was instilled in the conjunctival cul-de-sac of the right eye. After administration, the upper and lower eye lid were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material.

Observation period (in vivo):

1, 24, 48 and 72 hours; 7, 14, 21 and 25 days

Number of animals or in vitro replicates:

3

Details on study design:

Pre-test:
Prior to the in vivo testing, the test substance was also examined in the Chicken Enucleated Eye Test (CEET). The test substance caused severe reactions in the CEET.

Main Test:
Based on the results from this CEET it was decided to start with one rabbit. As severe signs of irritation were not observed in this rabbit, it was decided to continue the test with additional two rabbits.

SCORING SYSTEM: See Table 1.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

other: 24, 48 and 72 hours

Score:

1.66

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: The cornea score for two animals was 0 after 7 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: 24 , 48 and 72 hours

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: The iris score of two animals was 0 after 72 hours

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals

Time point:

other: 24, 48 and 72 hours

Score:

2.44

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: The conjunctivae score of two animals was 0 after 14 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: 24, 48 and 72 hours

Score:

1.22

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: The chemosis score of two animals was 0 after 14 days

Results 5

Irritation parameter:

other: ocular discharge

Basis:

mean

Remarks:

of three animals

Time point:

other: 24, 48 and 72 hours

Score:

1.55

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: The ocular discharge score of two animals was 0 after 72 hours

Irritant / corrosive response data:

At 1 hour after treatment, the eye effects observed in the three rabbits consisted of slight corneal opaicity, slight iritis, slight redness and moderate swelling of the conjunctivae, and severe ocular discharge. At 24 hours after treatment, the eye effects observed consisted of slight or moderate corneal opacity, slight iritis, moderate or severe redness and slight swelling of the conjunctivae, and slight or severe ocular discharge. At 48 hours after treatment, the eye effects observed consisted of slight or moderate corneal opacity, slight iritis (two rabbits), moderate or severe redness and slight or moderate swelling of the conjunctivae, and slight or severe ocular discharge. At 72 hours after treatment, the eye effects observed consisted of slight or moderate corneal opacity, slight iritis (one rabbit), slight, moderate or severe redness and slight or moderate swelling of the conjunctivae, and moderate ocular discharge (one rabbit). At 7 days after treatment, the eye effects observed consisted of slight corneal opacity and vascularization of the cornea in one rabbit, and slight redness and slight swelling of the conjunctivae in two rabbits. At 14 days after treatment, eye effects were still observed in one rabbit and consisted of slight corneal opacity, vascularisation of the cornea, and slight redness and slight swelling of the conjunctivae. At 21 days, these eye effects except minor vascularisation of the cornea had cleared completely. At 25 days, this eye effect had also cleared completely.

Other effects:

N.A.

Any other information on results incl. tables

Table 2: Individual scores awarded to the ocular lesions elicited by 2-etyhlhexyl lactate
rabbit number	corneal opacity	iris effects	conjunctivae		ocular discharge
			redness	chemosis
after one hour
37	1 (4)	1	1	2	3
29	1 (4)	1	1	2	3
30	1 (4)	1	1	2	3
after 24 hours
37	2 (4)	1	3	1	3
29	1 (4)	1	3	1	3
30	2 (2)	1	2	1	1
after 48 hours
37	2 (2)	1	3	1	1
29	2 (2)	1	3	2	3
30	1 (2)	0	2	1	1
after 72 hours
37	2 (2)	0	2	1	0
29	2 (4)	1	3	2	2
30	1 (1)	0	1	1	0
after 7 days
37	0	0	1	1	0
29	1 (4)*	0	1	1	0
30	0	0	0	0	0
after 14 days
37/30	0	0	0	0	0
29	1 (3)*	0	1	1	0
after 21 days
29	0*	0	0	0	0
after 25 days
29	0	0	0	0	0
(): area of opacity, 1= one quarter (or less) but not zero, 2= half area, 3= three quarter, 4= entire area
*= vascularization of the cornea; the degree diminshed gradually

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

2-ethylhexyl-lactate is distinctly irritating for the eyes of rabbits.

Executive summary:

In a primary eye irritation study (OECD 405), 0.1 mL of  2-etyhlhexyl lactate (purity ≥ 97 %) was instilled into the conjunctival sac of the right eye of three young adult New Zealand White rabbits. Animals then were observed for a maximum of 25 days. Irritation was scored by the method according to OECD guideline 405. The test substance caused moderate corneal opacity, slight iritis, moderate or severe redness and moderate swelling of the conjunctivae, and severe ocular discharge in the three rabbits. These adverse irritation effects were fully reversible within 21 days. In accordance to the CLP regulation 2-etyhlhexyl lactate needs to be classified in Category 2 (irritating to eyes).