Amoxicillin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 2015 to February 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test method according to OECD 423. GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate.

Cas Number:

61336-70-7

Molecular formula:

C16H25N3O8S

IUPAC Name:

(2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate.

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:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Husbandry of laboratory animals of the Experimental Medicine Centre at the Medical University in Białystok.
- Age at study initiation: 3 females at the first step were 8 weeks-old and the other 3 females were 10 week-old
- Weight at study initiation: 197.3 g (3 females first step) and 193.7 g (3 females second step)
- Fasting period before study: 19 hours
- Housing: Plastic cages (58x37x21 cm) covered with wire bar lids. Three animals per cage. UV-sterilized wood shavings were used as bedding.The environment of the animals was enriched by placing wooden blocks and nesting materials for laboratory animals in the cages.
- Diet (e.g. ad libitum): Murigran standard laboratory food ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 5 days

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

CMC sodium salt

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 mg test subtance/mL
- Amount of vehicle (if gavage): 0.5 mL/100 g b.w.
- Justification for choice of vehicle: Low water solubility, an attempt to disolve/suspend the test item in oil was conducted, solubility was weak. Carboxymthylcellulose sodium salt was used because his negligible toxicity.

DOSAGE PREPARATION
Shortly before the administration.

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the bibliographic toxicity data of the test subtance.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 in total, 3 female rats at the first step, 3 female rats at the second step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The general observation at least once a day, detailed clinical observations on the administration day, 10, 30 and 60 minutes after the administration and then at hourly intervals up to 5 hours, then once a day up to 14 days. Animals were weighed directly before the administration of the test item, on day 7 and 14 before euthanasia.
- Necropsy of survivors performed: yes, after the day 14th observation period, all surviving animals were euthanized and subjected to gross examination.
- Other examinations performed: clinical signs, body weight, gross examinations.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were recorded.

Clinical signs:

other: No signs of toxicity were stated.

Gross pathology:

The gross examination did not reveal any pathological changes.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral-LD50 for amoxicillin trihydrate in female rats is above 2000 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted according to the acute toxic class method (OECD 423) under GLP conditions. In a first step amoxicillin trihydrate was administered at a single dose of 2000 mg/kg bw to 3 Wistar female rats suspended in 0.5 carboxymethylcellullose sodium salt in a volume of 0.5 mL/100 g b.w. by gavage, at the second step the test item was adminstered to 3 additional female rats under the same conditions. After the administration the test animals were observed for 14 days, general and detailed clinical observations were performed on a daily basis, body weights were determined on day 0, 7 and 14. After the 14 -day observation period the animals were euthanized and subjected to detailed gross examination. All the tested animals survived the entire experiment, the examinations did not reveal any pathological change in the animals. The oral LD-50 for amoxicillin trihydrate is above 2000 mg/kg bw.