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

Skin irritation / corrosion

Administrative data

Endpoint:

skin 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The only differences were that the compound was evaluated on both intact and abraded skin following a 24-hour exposure, rather than only on intact skin followiing a 4-hour exposure as directed in the OECD Guidelines.

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:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Details on test material:

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

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 2.71 to 3.11 kg
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

Test system

Type of coverage:

occlusive

Preparation of test site:

other: one intacted and one abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

2 males, 1 female

Details on study design:

TEST SITE
- Area of exposure: approximately two inches square
- % coverage: The compound was covered with a 2x2 gauze patch that was also premoistened with deionized water.
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were gently wiped with a soft cloth and deionized water.
- Time after start of exposure: 24 h
SCORING SYSTEM: Draize, J.H., Woodard, G., and Calvery, H.O.: J. Pharmacol. exptl. Therap., 82:377-390,1944.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

ca. 0.22

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Intact skin, one fully reversed within 72 hours, the other two did not appear erythema.

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

ca. 0.44

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Abraded skin, two fully reversed within 72 hours, the other one did not appear erythema.

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Remarks on result:

other: Intact skin

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Remarks on result:

other: Abraded skin

Results 5

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: mean of 24 and 72 hours

Score:

0.25

Remarks on result:

other: mean of score in intact and abraded skin

Irritant / corrosive response data:

Following a 24-hour exposure to the compound, very slight (score =1), non-confluent erythema was apparent at both the intavt and the abraded site of one animal and at the abraded site of a second rabbit. No erythema was evident at either site in the third rabbit, and there was no edema at any of the application sites. There was no obvious change at any of the sites at 48 hours post dose. However, by 72 hours post dose, the erythema had subsided completely, and the skin at each intact and abraded site appeared essentially normal.

Other effects:

Throughout the 72-hour observation period, all animals remained alert and active, but the food consumption of one rabbit was reduced. The final body weight of each rabbit was essentially comparable to the animal's pre-test weight.

Any other information on results incl. tables

Individual Skin Reactions Following 24-Hour Exposure

Condition of skin	Observation period (hours)	Rabbit No.
		1		2		3
		Erythema	Edema	Erythema	Edema	Erythema	Edema
Intact	24	1	0	0	0	0	0
	48	1	0	0	0	0	0
	72	0	0	0	0	0	0
Abraded	24	1	0	0	0	1	0
	48	1	0	0	0	1	0
	72	0	0	0	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 results of this reveal that the Primary Irritation Score is 0.25, indicating that the test substance produced only negligible irritation on rabbit skin and is therefore not a primary skin irritant.