(25S)-25-Cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydroavermectin A1a

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:

key study

Study period:

During June of 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar 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:

(2aE,4E,8E)-(5'S,6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-6'-Cyclohexyl-5',6,6',7,10,11,14,15,17a,20,20a,20b-dodecahydro-20,20b-dihydroxy-5',6,8,19-tetramethyl-17-oxospiro(11,15-methano-2H,13H,17H-furo(4,3,2-pq)(2,6)benzodioxacyclooctadecin-13,2'-(2H)pyran)-7-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-alpha-L-arabino-hexopyranosyl)-3-O-methyl-alpha-L-arabino-hexopyranoside

Cas Number:

117704-25-3

Molecular formula:

C50H74O14

IUPAC Name:

(2aE,4E,8E)-(5'S,6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-6'-Cyclohexyl-5',6,6',7,10,11,14,15,17a,20,20a,20b-dodecahydro-20,20b-dihydroxy-5',6,8,19-tetramethyl-17-oxospiro(11,15-methano-2H,13H,17H-furo(4,3,2-pq)(2,6)benzodioxacyclooctadecin-13,2'-(2H)pyran)-7-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-alpha-L-arabino-hexopyranosyl)-3-O-methyl-alpha-L-arabino-hexopyranoside

Constituent 2

Reference substance name:

Avermectin A(sub 1a), 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-

IUPAC Name:

Avermectin A(sub 1a), 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Batch No.: 19101-164-1
Purity: not specified

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.79 to 2.96 kg

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a dose (18.8 mg) equivalent to a volume of 0.1 mL
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 males, 1 female

Details on study design:

A dose of 18.8 mg (the amount of compound equivalent to a volume of 0.1 mL) of the test substance was instilled into the conjunctivasl sac of the left of each the three rabbits (2 males, 1 female); the right eye of each animal served as an untreated control. The eyes were not rinsed after dosing.
All animals were observed 3 days. on the day of dosing (day 1), the eyes were evaluated wuth minimal manipulation and without the use of fluorescein.
The scoring system used was that of Draize.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: One animal appeared at 1 hour but fully reversible within 24 hours.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

ca. 0.11

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Two animals appeared, one fully reversible within 24 hours, the other one fully reversible within 48 hours.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Two animals appeared at 1 hour but fully reversible within 24 hours.

Irritant / corrosive response data:

Immediately after dosing, each rabbit blinked and rubbed the treated eye; however, none of the rabbits exhibited sign of obvious pain or discomfort. Within 1 hour of dosing, slight circumcorneal reddening was apperent in the treated eye of each rabbit. Slight comjuctival reddening and chemosis was also evident in two of the rabbits, and iritis was apperent in the treated eye of one of these animals. By 6 hours post dose, the ocular changes were subsiding, and at 24 hours, the only changes noted were slight circumcorneal reddening in one rabbit and slight reddening of the conjuctivae in another animal. By 48 hours post dose, the treated eye of each rabbit appeared normal.

Other effects:

All rabbits were asymptomatic throughout the 72-hour test period, and they all gained weight.

Any other information on results incl. tables

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number	Time after application	Cornea opacity	Iris	Conjunctivae
				Redness	Chemosis
1	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	1 1 0 0	1 0 0 0
2	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0
3	1 hour 24 hours 48 hours 72 hours	0 0 0 0	1 0 0 0	1 0 0 0	1 0 0 0

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test indicated that the test substance is not an ocular irritant in rabbits because a positive irritating effect was not apperent in any of the treated eyes at 24, 48, or 72 hours post dose.