Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-08-26 to 1991-10-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection 1990-05-14

Test material

Test material information

Constituent 1

Reference substance name:

Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)

EC Number:

931-276-9

Cas Number:

114959-46-5

Molecular formula:

See information in Section 1.2.

IUPAC Name:

Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)

Details on test material:

- Name of test material (as cited in study report): [CAS Number 114959-46-5]
- Physical state: Clear brown viscous liquid
- Lot/batch No.: 191 (Stanlow); DSP4767/91
- Toxicology reference number: ST91/247
- Stability under test conditions: Stable for the duration of the study under the test conditions employed
- Storage condition of test material: In the dark at ambient temperature under nitrogen
- Date received: 08 August 1991

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield Farms UK Ltd
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 3.38-4.38 kg (males); 3.42-4.506 kg (females)
- Fasting period before study:
- Housing: Singly in hanging, stainless steel cages with perforated dimple or wire-mesh flooring. Sawdust-filled undertrays for excreta were placed beneath each cage and changed twice weekly. Each cage measured 91 cm x 66 cm x 45 cm.
- Diet (e.g. ad libitum): Pelleted diet (Standard Rabbit Diet, SQC, Special Diet Services Ltd) ad libitum
- Water (e.g. ad libitum): Water from the public supply ad libitum
- Acclimation period: At least two weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 15-20 degrees Centigrade with animal room temperature exceeding the target range by up to 0.3 degrees Centigrade on five days. However, these excusions had no apparent effect on the health of the animals.
- Humidity: 30-70 % with animal room humidity exceeding the target range for more than two consecutive (4-hourly) recordings on eight days of the study. However, these excusions had no apparent effect on the health of the animals.
- Photoperiod: 12 hour day and 12 hour night provided by automatically controlled fluorescent lighting

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL of undiluted test material

Duration of treatment / exposure:

Single application

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

Animals with eyes free from irritation, occular defects or corneal injury were used. The undiluted test material was placed into the lower conjunctival sac of one eye of each animal. The treated eye was gently held closed for a few seconds to prevent loss of the test material. The eyes were not irrigated.

The immediate reactions of the rabbits were scored as an initial pain response using a six point scale (see Attachment A). Other ocular reactions to treatment were noted and scored using standard grades (see Attachment A). The mean scores at each time point and the group mean scores at 24, 48 and 72 hours were calculated.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal: 479M

Time point:

other: 1 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal: 479M

Time point:

other: 4 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: 479M

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: 479M

Time point:

48 h

Score:

1

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: 479M

Time point:

72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

chemosis score

Basis:

animal: 479M

Time point:

other: 1h

Score:

0

Max. score:

0

Results 7

Irritation parameter:

chemosis score

Basis:

animal: 479M

Time point:

other: 4 h

Score:

1

Reversibility:

fully reversible within: 48 h

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 479M

Time point:

24 h

Score:

0

Max. score:

0

Results 9

Irritation parameter:

chemosis score

Basis:

animal: 479M

Time point:

48 h

Score:

0

Max. score:

0

Results 10

Irritation parameter:

chemosis score

Basis:

animal: 479M

Time point:

72 h

Score:

0

Max. score:

0

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal: 479M

Time point:

other: 1h

Score:

0

Max. score:

0

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal: 479M

Time point:

other: 4h

Score:

0

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal: 479M

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 14

Irritation parameter:

iris score

Basis:

animal: 479M

Time point:

other: 1h

Score:

0

Max. score:

0

Results 15

Irritation parameter:

iris score

Basis:

animal: 479M

Time point:

other: 4 h

Score:

0

Max. score:

0

Results 16

Irritation parameter:

iris score

Basis:

animal: 479M

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 17

Irritation parameter:

conjunctivae score

Basis:

animal: 539M

Time point:

other: 1 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72h

Results 18

Irritation parameter:

conjunctivae score

Basis:

animal: 539M

Time point:

other: 4 h

Score:

2

Max. score:

2

Results 19

Irritation parameter:

conjunctivae score

Basis:

animal: 539M

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 20

Irritation parameter:

conjunctivae score

Basis:

animal: 539M

Time point:

48 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 21

Irritation parameter:

conjunctivae score

Basis:

animal: 539M

Time point:

72 h

Score:

0

Results 22

Irritation parameter:

chemosis score

Basis:

animal: 539M

Time point:

other: 1h

Score:

1

Reversibility:

fully reversible within: 72h

Results 23

Irritation parameter:

chemosis score

Basis:

animal: 539M

Time point:

other: 4h

Score:

2

Reversibility:

fully reversible within: 72h

Results 24

Irritation parameter:

chemosis score

Basis:

animal: 539M

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 25

Irritation parameter:

chemosis score

Basis:

animal: 539M

Time point:

48 h

Score:

0

Results 26

Irritation parameter:

chemosis score

Basis:

animal: 539M

Time point:

72 h

Score:

0

Results 27

Irritation parameter:

cornea opacity score

Basis:

animal: 539M

Time point:

other: 1h

Score:

0

Results 28

Irritation parameter:

cornea opacity score

Basis:

animal: 539M

Time point:

other: 4h

Score:

0

Results 29

Irritation parameter:

cornea opacity score

Basis:

animal: 539M

Time point:

24/48/72 h

Score:

0

Results 30

Irritation parameter:

iris score

Basis:

animal: 539M

Time point:

other: 1h

Score:

0

Results 31

Irritation parameter:

iris score

Basis:

animal: 539M

Time point:

other: 4h

Score:

0

Results 32

Irritation parameter:

iris score

Basis:

animal: 539M

Time point:

24/48/72 h

Score:

0

Results 33

Irritation parameter:

conjunctivae score

Basis:

animal: 540M

Time point:

other: 1h

Score:

1

Reversibility:

fully reversible within: 72h

Results 34

Irritation parameter:

conjunctivae score

Basis:

animal: 540M

Time point:

other: 4h

Score:

1

Reversibility:

fully reversible within: 72h

Results 35

Irritation parameter:

conjunctivae score

Basis:

animal: 540M

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 36

Irritation parameter:

conjunctivae score

Basis:

animal: 540M

Time point:

48 h

Score:

0

Results 37

Irritation parameter:

conjunctivae score

Basis:

animal: 540M

Time point:

72 h

Score:

0

Results 38

Irritation parameter:

chemosis score

Basis:

animal: 540M

Time point:

other: 1h

Score:

0

Results 39

Irritation parameter:

chemosis score

Basis:

animal: 540M

Time point:

other: 4h

Score:

1

Reversibility:

fully reversible within: 72h

Results 40

Irritation parameter:

chemosis score

Basis:

animal: 540M

Time point:

24/48/72 h

Score:

0

Results 41

Irritation parameter:

cornea opacity score

Basis:

animal: 540M

Time point:

other: 1h

Score:

0

Results 42

Irritation parameter:

cornea opacity score

Basis:

animal: 540M

Time point:

other: 4h

Score:

0

Results 43

Irritation parameter:

cornea opacity score

Basis:

animal: 540M

Time point:

24/48/72 h

Score:

0

Results 44

Irritation parameter:

iris score

Basis:

animal: 540M

Time point:

other: 1h

Score:

0

Results 45

Irritation parameter:

iris score

Basis:

animal: 540M

Time point:

other: 4h

Score:

0

Results 46

Irritation parameter:

iris score

Basis:

animal: 540M

Time point:

24/48/72 h

Score:

0

Results 47

Irritation parameter:

conjunctivae score

Basis:

animal: 544F

Time point:

other: 1h

Score:

1

Reversibility:

fully reversible within: 72h

Results 48

Irritation parameter:

conjunctivae score

Basis:

animal: 544F

Time point:

other: 4h

Score:

1

Reversibility:

fully reversible within: 72h

Results 49

Irritation parameter:

conjunctivae score

Basis:

animal: 544F

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 50

Irritation parameter:

conjunctivae score

Basis:

animal: 544F

Time point:

48 h

Score:

0

Results 51

Irritation parameter:

conjunctivae score

Basis:

animal: 544F

Time point:

72 h

Score:

0

Results 52

Irritation parameter:

chemosis score

Basis:

animal: 544F

Time point:

other: 1h

Score:

0

Results 53

Irritation parameter:

chemosis score

Basis:

animal: 544F

Time point:

other: 4h

Score:

0

Results 54

Irritation parameter:

chemosis score

Basis:

animal: 544F

Time point:

24/48/72 h

Score:

0

Results 55

Irritation parameter:

cornea opacity score

Basis:

animal: 544F

Time point:

other: 1h

Score:

0

Results 56

Irritation parameter:

cornea opacity score

Basis:

animal: 544F

Time point:

other: 4h

Score:

0

Results 57

Irritation parameter:

cornea opacity score

Basis:

animal: 544F

Time point:

24/48/72 h

Score:

0

Results 58

Irritation parameter:

iris score

Basis:

animal: 544F

Time point:

other: 1h

Score:

0

Results 59

Irritation parameter:

iris score

Basis:

animal: 544F

Time point:

other: 4h

Score:

0

Results 60

Irritation parameter:

iris score

Basis:

animal: 544F

Time point:

24/48/72 h

Score:

0

Results 61

Irritation parameter:

conjunctivae score

Basis:

animal: 545F

Time point:

other: 1h

Score:

1

Reversibility:

fully reversible within: 72h

Results 62

Irritation parameter:

conjunctivae score

Basis:

animal: 545F

Time point:

other: 4h

Score:

1

Reversibility:

fully reversible within: 72h

Results 63

Irritation parameter:

conjunctivae score

Basis:

animal: 545F

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 64

Irritation parameter:

conjunctivae score

Basis:

animal: 545F

Time point:

48 h

Score:

0

Results 65

Irritation parameter:

conjunctivae score

Basis:

animal: 545F

Time point:

72 h

Score:

0

Results 66

Irritation parameter:

chemosis score

Basis:

animal: 545F

Time point:

other: 1h

Score:

0

Results 67

Irritation parameter:

chemosis score

Basis:

animal: 545F

Time point:

other: 4h

Score:

0

Results 68

Irritation parameter:

chemosis score

Basis:

animal: 545F

Time point:

24/48/72 h

Score:

0

Results 69

Irritation parameter:

cornea opacity score

Basis:

animal: 545F

Time point:

other: 1h

Score:

0

Results 70

Irritation parameter:

cornea opacity score

Basis:

animal: 545F

Time point:

other: 4h

Score:

0

Results 71

Irritation parameter:

cornea opacity score

Basis:

animal: 545F

Time point:

24/48/72 h

Score:

0

Results 72

Irritation parameter:

iris score

Basis:

animal: 545F

Time point:

other: 1h

Score:

0

Results 73

Irritation parameter:

iris score

Basis:

animal: 545F

Time point:

other: 4h

Score:

0

Results 74

Irritation parameter:

iris score

Basis:

animal: 545F

Time point:

24/48/72 h

Score:

0

Results 75

Irritation parameter:

conjunctivae score

Basis:

animal: 546F

Time point:

other: 1h

Score:

1

Reversibility:

fully reversible within: 72h

Results 76

Irritation parameter:

conjunctivae score

Basis:

animal: 546F

Time point:

other: 4h

Score:

1

Reversibility:

fully reversible within: 72h

Results 77

Irritation parameter:

conjunctivae score

Basis:

animal: 546F

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 72h

Results 78

Irritation parameter:

conjunctivae score

Basis:

animal: 546F

Time point:

48 h

Score:

0

Results 79

Irritation parameter:

conjunctivae score

Basis:

animal: 546F

Time point:

72 h

Score:

0

Results 80

Irritation parameter:

chemosis score

Basis:

animal: 546F

Time point:

other: 1h

Score:

0

Results 81

Irritation parameter:

chemosis score

Basis:

animal: 546F

Time point:

other: 4h

Score:

1

Reversibility:

fully reversible within: 72h

Results 82

Irritation parameter:

chemosis score

Basis:

animal: 546F

Time point:

24 h

Score:

0

Results 83

Irritation parameter:

chemosis score

Basis:

animal: 546F

Time point:

48 h

Score:

0

Results 84

Irritation parameter:

chemosis score

Basis:

animal: 546F

Time point:

72 h

Score:

0

Results 85

Irritation parameter:

cornea opacity score

Basis:

animal: 546F

Time point:

other: 1h

Score:

0

Results 86

Irritation parameter:

cornea opacity score

Basis:

animal: 546F

Time point:

other: 4h

Score:

0

Results 87

Irritation parameter:

cornea opacity score

Basis:

animal: 546F

Time point:

24/48/72 h

Score:

0

Results 88

Irritation parameter:

iris score

Basis:

animal: 546F

Time point:

other: 1h

Score:

0

Results 89

Irritation parameter:

iris score

Basis:

animal: 546F

Time point:

other: 4h

Score:

0

Results 90

Irritation parameter:

iris score

Basis:

animal: 546F

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

There was no initial pain response upon administration of the test material. Conjunctival reactions to ocular instillation of the test material did not exceed a crimson-red appearance, chemosis causing partial eversion of the eyelids and a slight ocular discharge. Such reactions resolved within 48 hours (chemosis) and 72 hours (redness) of treatment. The cornea and iris remained overtly unaffected by the test material.

Other effects:

No data

Applicant's summary and conclusion

Conclusions:

There was no initial pain response upon administration of the test substance. Single instillation of the undiluted test material into one ocular sac of each of six rabbits caused conjunctival irritation that resolved within 72 hours of treatment. The most intense irritation reactions did not exceed a crimson red appearance, chemosis causing partial eversion of the eyelids and slight ocular discharge.