Amoxicillin

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD 402 and EU method B3 with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

612-127-4

EC Number:

612-127-4

Cas Number:

61336-70-7

Molecular formula:

C16H19N3O5S.3H2O

IUPAC Name:

612-127-4

Constituent 2

Reference substance name:

Amoxicillin trihydrate

IUPAC Name:

Amoxicillin trihydrate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Amoxicillin trihydrate
- Physical state: White solid powder
- Analytical purity: 98.7 %
- Purity test date: 28/10/2015
- Lot/batch No.: B334172
- Expiration date of the lot/batch: October 2020
- Storage condition of test material: Room temperature in a container made of plastic, glass or metal.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar male and female rats (Cmdb: WI; outbred).
- Source:obtained from the husbandry of laboratory animals of the Experimental Medicine Centre at the Medical University in Białystok.
- Age at study initiation: males 8 week old, females 10 week old.
- Weight at study initiation: average body weight males 249.8 and females 203.6 g.
- No fasting period before study.
- Housing: plastic cages covered with wire bar lids, dimensions 58 x 37 x 21 cm. UV-sterilized wood shavings were used as bedding, and the environment was enriched with wooden blocks and nesting materials for laboratory animals.
- After application of the test item, each animal was housed individually.
- After removal of the test item, group housing (5 animals of the same sex per cage).
- Diet: ad libitum access to "Murigran" standard granulated fodder (batch number: 7/15, 8/15 and 1/15) produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz
- Water: ad libitum access to tap water.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24.
- Humidity (%): 25-50.
- Air changes (per hr): 16.
- Photoperiod (hrs dark / hrs light): 12h light / 12h dark.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- One day before the test, fur from the dorsal area of the trunks of the animals was shaved with an electric shaver.
- Area of exposure: 30-45cm2
- % coverage: 10% of the body surface area.
- Type of wrap if used: gauze patches.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test item was removed using water.
- Time after start of exposure: 24h.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw.
- The test item, in form of powder, was applied to gauze patches, and moistened of a few drops of water.

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: the observation of all animals for mortality and morbidity was conducted twice a day or once a day (on days off). The detailed clinical observations were made on the application day (day 0) at hourly intervals up to 5 hours. From the 1st to the 14th day of the experiment, the detailed clinical observations were performed once a day.
- Body weights of the animals were determined on days 0 (directly before the application of the test item), 7, and 14 (before euthanasia).
- After the 14-day observation period, all animals were euthanized by intraperitoneal administration of morbital at a dose of 200 mg/kg b.w. and transferred to a detailed gross examination: observation of the external body surface, all natural apertures, and the cranial, thoracic, and abdominal cavities with their contents.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were recorded.

Clinical signs:

other: No clinical signs were noticed.

Gross pathology:

The gross examination did not reveal any pathological changes in the examined animals.

Any other information on results incl. tables

During the experiment, the air temperature dropped below 19ºC a few times, and the relative air humidity dropped below 30% a few times. These changes were temporary and did not influence the study course and results.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dermal-LD50 > 2000 mg/kg bw.

Executive summary:

An study of acute dermal toxicity on rats was performed for the test substance amoxicillin trihydrate according to OECD No.402 and EU method B3 under GLP conditions. Amoxicillin trihydrate at a single dose of 2000 mg/kg body weight was applied to the shaved dorsal area of the trunks of 5 males and 5 females. After the application of the test item, the animals were observed for 14 days. General and detailed clinical observations of all animals were performed daily during the entire experiment. Body weights of the animals were determined on days 0, 7, and 14. After the 14-day observation period, the animals were euthanized, dissected, and subjected to detailed gross examinations.Based on the results of the study, the dermal-LD50 is greater than 2000mg/kg bw.