R-AMINR

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

419-800-1

EC Name:

-

Cas Number:

112101-81-2

Molecular formula:

C10H16N2O3S

IUPAC Name:

(R)-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl: CD.BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Five to seven weeks old
- Weight at study initiation: Males 163 to 188 g and females 145 to 162 g
- Fasting period before study: Yes (18 hours prior to dosing until 3 hours after dosing).
- Housing: Up to 5 rats of the same sex were accommodated in suspended stainless steel mesh cages.
- Diet (e.g. ad libitum): SQC(E) rat and mouse maintenance diet No. 1 was freely available to the animals at all times except for a period of fasting.
- Water (e.g. ad libitum): Mains water was provided ad libitum via cage mounted water bottles.
- Acclimation period: At least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 40 to 70% relative humidity
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: standard vehicle

MAXIMUM DOSE VOLUME APPLIED: 10 mL/Kg

DOSAGE PREPARATION (if unusual): The test article was dispersed in corn oil and all formulations were used on the day of preparation.

Doses:

Preliminary test: 500 and 2000 mg/kg
Main test: 2000 mg/kg

No. of animals per sex per dose:

Five males and five females in the main phase

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were noted once within 30 minutes of dosing, four times within the first 4 hours of dosing, twice daily on days 2, 3 and 4 then once daily from the 5th onwards. Bodyweights were recorded on day -1, Day 1, 8 and 15.
- Necropsy of survivors performed: yes. The necropsy procedure included inspection of external thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.
- Other examinations performed:

Statistics:

Not required

Results and discussion

Preliminary study:

Groups of one fasted female rat dosed at 500 or 1000 mg/kg/day. All animals survived.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died following a single oral dose.

Clinical signs:

other: Two males were lethargic approximately four hours after dosing on Day 1 but this had resolved by day 2. Staining of teh snout was apparent in all rats during Day 2 and the female rats also showed soiling of the anogenital region.

Gross pathology:

Necropsy at termination revealed enlargement or red foci on the mandibular lymph nodes of 5 rats, reddening of the thymus in two rats and single cases of a small uterus or renal pelvic dilatation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose of the test substance to rats was found to exceed 2000 mg/kg (the standard limit dose for such studies).