Avermectin A1a, 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 08 to 23 Apr 2015

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:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(1'R,2S,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-6-cyclohexyl-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-5,6-dihydro-3',7',19'-trioxaspiro[pyran-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one

EC Number:

601-490-4

Cas Number:

117704-25-3

Molecular formula:

C50H74O14

IUPAC Name:

(1'R,2S,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-6-cyclohexyl-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-5,6-dihydro-3',7',19'-trioxaspiro[pyran-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Batch No.: DOA0140431
Purity: 97.4%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Age at study initiation: The animals were approximately 8 weeks old at the time of dose administration
- Weight at study initiation: body weight values ranged from 258 g to 279 g for males and 185 g to 200 g for females, ± 20% of the mean for each sex.
- Fasting period before study:
- Housing: all animals were housed individually in clean, stainless steel, wire-mesh cages suspended above cage board.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.3°C to 21.4°C
- Humidity (%): ranged from 39.1% to 58.4%
- Air changes (per hr): a minimum of 10 fresh air changes per hour
- Photoperiod (hrs dark / hrs light): a 12-hour light (0600 hours to 1800 hours)/12-hour dark photoperiod

Administration / exposure

Type of coverage:

semiocclusive

Details on dermal exposure:

TEST SITE
- Area of exposure: at least 10% of the total body surface
- Type of wrap if used: Each dose was applied to the unabraded skin and overwrapped with gauze binders (<8-ply) that were secured with nonirritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Upon completion of exposure, the bandages were removed and the sites were wiped with disposable paper towels moistened with tepid tap water.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

one group of 5 male and 5 female rats

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days

MORTALITY
The rats were observed for mortality and moribundity at approximately 1, 2, and 4 hours post-application on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.

CLINICAL OBSERVATIONS
The rats were observed at approximately 1, 2, and 4 hours post-application on study day 0 and once daily thereafter for 14 days. Observations included, but were not limited to, evaluation for changes in appearance of skin and fur, eyes, mucous membranes, respiratory and circulatory systems, autonomic effects, and central nervous system effects.

DERMAL OBSERVATIONS
The application sites were observed for erythema, edema, and other dermal findings approximately 30-60 minutes after bandage removal and daily thereafter through study day 14.

BODY WEIGHTS
Body weights were obtained and recorded on study days 0 (initiation), 7, and 14 (termination).

NECROPSY
Upon termination, all rats were euthanized by carbon dioxide inhalation. The major organ systems of the cranial, thoracic, and abdominal cavities and the eyes, skin, and application site were examined for all animals. Tissues were discarded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: Clinical observations were limited to colored material (red, yellow, and/or brown) on various body surfaces (around nose and mouth and/or on anogenital area) for 2 males and 1 female, dermal atonia for 1 male, and soft feces for 1 male on 1 or 2 occasions

Gross pathology:

There were no gross necropsy findings for any examined tissues.

Other findings:

There were no dermal findings noted during the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, the LD50 of the test substance was greater than 2000 mg/kg when administered once dermally for 24 hours to the clipped, unabraded skin of male and female albino rats.