(2R)-2-(2-chlorophenyl)-2-hydroxyethanoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The potential of the test item SR94653 to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th February 1987) and EC (92/69/EEC, B.5, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2R)-2-(2-chlorophenyl)-2-hydroxyethanoic acid

EC Number:

444-040-0

EC Name:

(2R)-2-(2-chlorophenyl)-2-hydroxyethanoic acid

Cas Number:

52950-18-2

Molecular formula:

Hill formula: C8H7ClO3 CAS formula: C8H7CLO3

IUPAC Name:

(2R)-2-(2-chlorophenyl)-2-hydroxyacetic acid

Details on test material:

- Name of test material (as cited in study report): (R)-2-chloromandelic acid
- Physical state: white powder
- Analytical purity: 99.7 %
- Lot/batch No.: 1500175 and CR-UY-002
- Stability under test conditions: guaranteed by the sponsor
- Storage condition of test material: at room temperature
- Other: The correspondence between both batch numbers (1500175 at receipt and CR-UY-002 on the analytical certificate) was confirmed by the Study Monitor in a statement dated 11 June 2001

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Weight at study initiation: on the day of treatment, die animals had a mean body weight ± standard deviation of 3.1 ± 0.1 kg.
- Housing: individual
- Diet: 110 pelleted diet (UAR. Villemoisson, Epinay-sur-Orge, France) ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30-70
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12/12

The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals. The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.

Food is analysed regularly by die supplier for composition and contaminant levels.
Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines). No contaminants were known to have been present in the diet or drinking water at levels which
may be expected to have interfered with or prejudiced the outcome of the study.

Test system

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Amount applied: 100 other: mg

Duration of treatment / exposure:

not applicable because eyes were not rinsed and the test substance remained in the eye as long as watered out

Observation period (in vivo):

2 weeks

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM:
Ocular reactions were scored according to die following numerical scale:

Conjunctival lesions and discharge

Chemosis (lids and/or nictitating membranes)
0 no swelling
1 any swelling above normal (includes nictitating membranes)
2 obvious swelling with partial eversion of lids
3 swelling with lids about half-closed
4 swelling with lids more than half-closed

Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
0 blood vessels normal
1 number of blood vessels definitely hyperemic (injected)
2 diffuse, crimson colour, individual vessels not easily discernible
3 diffuse, beefy red

Discharge
0 absence of discharge
1 slight discharge (does not include small amounts normally found in inner canthus)
2 discharge with moistening of lids and hairs adjacent to lids
3 discharge with moistening of lids and hairs on wide area around the eye

Iris lesions
0 normal
1 markedly deepened rugae, congestion, swelling, moderate circum-corneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 no reaction to light, hemorrhage, gross destruction (any or all of these)

Corneal lesions
Degree of opacity (area most dense taken for reading)
0 no ulceration or Opacity
1 scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible
2 easily discernible translucent area, details of iris slightly obscured
3 nacreous areas, no details of iris visible, size of pupil barely discernible
4 opaque cornea, iris not discernible through the opacity

Area of opacity
1 one quarter (or less) but not zero
2 greater than one quarter but less than a half
3 greater than one half but less than three quarters
4 greater than three quarters up to whole area

Any other lesions observed were noted.

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

1-3

Time point:

other: 24 hours

Score:

4

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

1-2

Time point:

other: 24 hours

Score:

1

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

1-3

Time point:

other: 24 hours

Score:

3

Max. score:

4

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

1-3

Time point:

other: 24 hours

Score:

3

Max. score:

4

Any other information on results incl. tables

Results

On day 1, moderate conjunctival reactions (chemosis and clear discharge) were observed in all animals. A moderate to marked corneal opacity, sometimes covering the whole area of the cornea, was noted in all three animals. No signs of iritis were recorded in 2/3 animals; the iris was masked by the marked corneal opacity in the remaining animal.

 

On day 2, chemosis and redness of the conjunctivae became marked; discharge became whitish purulent. A whitish area was observed on the conjunctivae of all three animals. Signs of iritis were recorded in 2/3 animals and iris was still masked by the marked corneal opacity in the remaining animal.

 

Readings	Animal	Cornea		Iris	Conjunctiva			Additional findings
		op	ar		red	ch	di
1 h	1	3	3	0	0	2	2
	2	2	4	0	0	2	2
	3	3	4	OP	0	2	2
24 h	1	4	2	1	3	3	S	ZB
	2	4	3	1	3	3	S	ZB
	3	4	4	OP	3	3	S	ZB

 

Symbols:

 

OP: Scoring masked by marked corneal opacity

S: whitish purulent discharge

ZB: whitish area on conjunctivae

 

A severe corneal opacity, covering the whole area of the cornea in 1/3 animals, was noted in all three animals. Due to the severe ocular reactions observed, the animals were killed for humane reasons after the 24-hour reading.

 

Conclusion

Under our experimental conditions, the test item SR94653 is severely irritant when administered by ocular route to rabbits.

Applicant's summary and conclusion

Interpretation of results:

highly irritating

Remarks:

Migrated information

Conclusions:

Classification: risk of serious damage to eyes