Rifamycin, 3-amino-1,4-dideoxy-1,4-dihydro-4-imino-1-oxo-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2017-03-30 to 2017-06-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Rifamycin, 3-amino-1,4-dideoxy-1,4-dihydro-4-imino-1-oxo-

Cas Number:

62041-01-4

Molecular formula:

C37 H47 N3 O11

IUPAC Name:

Rifamycin, 3-amino-1,4-dideoxy-1,4-dihydro-4-imino-1-oxo-

Specific details on test material used for the study:

Batch: 16012R87A
Purity: not specified

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source: Charles River Deutschland, Sulzfeld, Germany
Age at study initiation: Young adult animals (approximately 8-9 weeks old) were selected
Weight at study initiation: 151 to 190 g
Housing: On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized sawdust as bedding material equipped with water bottles.
Diet: Pelleted rodent diet was provided ad libitum throughout the study.
Water: Municipal tap-water was freely available to each animal via water bottles.
Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
Temperature (°C): 18°C to 24°C (Target), 21 to 22°C (Actual)
Humidity (%): 40% to 70% (Target), 43 to 53% (Actual)
Air changes (per hr): Ten or greater
Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
Amount of vehicle: 10 mL/kg body weight was used for each dose
Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure.

CLASS METHOD
Rationale for the selection of the starting dose:The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Each dose group consisted of 3 animals

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
Frequency of observations and weighing: Mortality/Viability: Twice daily. Body weights: Days 1 (predose), 8 and 15. Clinical signs: at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
Other examinations performed: no.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: Hunched posture and/or piloerection were noted for five out of six animals on Day 1

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

other: do not have to be classified

Conclusions:

LD50 >2000 mg/kg body weight

Executive summary:

The study was carried out in compliance with OECD 423 (2001) guideline, the test substance was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

The oral LD50 value of test item in Wistar rats was established to exceed 2000 mg/kg body weight. The LD50 cut-off value was considered to exceed 5000 mg/kg body weight.