Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C11-17 and C17 unsatd. alkyl) derivs. and sodium hydroxide and 2-propenoic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

5-day dose-range finding study

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2007-04-16 to 2007-04-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The purpose of this study was to assess the tolerance of rats to exposure of the test item for 5 days. The results of this study were used to select the dose levels for the 28-day toxicity study.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

EC Number:

264-761-2

EC Name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Cas Number:

64265-45-8

IUPAC Name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Test material form:

liquid

Details on test material:

- Physical state: liquid
- Analytical purity: 97.0%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 6 weeks.
- Fasting period before study: no
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNlFF Spezialdiaten GmbH, Soest, Germany
- Water (e.g. ad libitum): Free access to tap water.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
The test substance was administered undiluted.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

5 days

Frequency of treatment:

Once daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Dose selection rationale: Dose were based on the results of the acute oral toxicity study (report no. 484827)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least once daily

BODY WEIGHT: Yes
- Time schedule for examinations: days 1 and 5

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean over days 1-5 diet consumption calculated as g food/kg body weight/day

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals assigned to the study

ORGAN WEIGHTS: Kidneys, Liver

HISTOPATHOLOGY: No

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

One animal in the 1000 mg/kg bw/d group showed salivation between Days 3 and 5. No further clinical signs noted.

Mortality:

no mortality observed

Description (incidence):

No mortality.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Normal

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Normal

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Liver weights considered to be normal and kidney weights were considered to be slightly increased in the 1000 mg/kg group

Gross pathological findings:

no effects observed

Description (incidence and severity):

No abnormalities noted.

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Effect levels

Dose descriptor:

other: selection of dose levels for subsequent 28-day toxicity study

Basis for effect level:

other: Based on the results of this dose range finding study, dose levels of 0, 50, 150 and 1000 mg/kg bw/day were considered suitable for the subsequent 28-day toxicity tests in the Wistar rat.

Remarks on result:

not measured/tested

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Based on the results of this dose range finding study, dose levels of 0, 50, 150 and 1000 mg/kg bw/d were considered suitable for the subsequent 28-day toxicity test in the Wistar rat.

Executive summary:

In a subacute toxicity study Amphopropionate C8 (50.6% a.i.) was administered to 3 female Wistar rats per dose orally by gavage once daily at dose levels of 500 and 1000 mg/kg bw/day for 5 consecutive days. The purpose of this study was to assess the tolerance of rats to exposure of the test item for 5 days. The results of this study were used to select the dose levels for the 28-day toxicity study.

All animals survived the scheduled study period. Treatment with the test item at the dose level of 1000 mg/kg bw/day caused a slightly increased kidney weight and one animal of the high dose group showed salivation between Day 3 and 5. No further test substance-related findings were detected or observed in clinical examinations, body weights, food consumption values and clinical pathology evaluations including organ weight analysis.

Based on these results, dose levels of 0, 50, 150 and 1000 mg/kg bw/d were considered suitable for the subsequent 28 day toxicity test.