2,2'-(cyclohexylimino)bisethanol

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February - July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-(cyclohexylimino)bisethanol

EC Number:

224-809-5

EC Name:

2,2'-(cyclohexylimino)bisethanol

Cas Number:

4500-29-2

Molecular formula:

C10H21NO2

IUPAC Name:

2,2'-(cyclohexylimino)bisethanol

Constituent 2

Reference substance name:

2,2`-(cyclohexylimino)bisethanol

IUPAC Name:

2,2`-(cyclohexylimino)bisethanol

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wistar rat, Crl: WI(Han) (SPF), Charles River, Germany
- Age at study initiation: 7-8 weeks (males); 7-8 weeks (females)
- Weight at study initiation: 132-178 g (males); 123-138 g (females)
- Fasting period before study: over night
- Housing: individual housing in IVC cages, type III H
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hourd light / dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

7 days/week, for 28 days

Frequency of treatment:

once daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
12 mg/kg
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
30 mg/kg
Basis:
actual ingested

Doses / concentrations 4

Remarks:

Doses / Concentrations:
75 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on 14 day dose-range finder
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: n.a.
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random): random

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: at beginning of treatment and weekly thereafter

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:before tretament, last week of treatments, end of recovery period
- Dose groups that were examined: all animals

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after last administration
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: all surviving animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after last administration
- Animals fasted: No
- How many animals: all surviving animls

URINALYSIS: Yes
- Time schedule for collection of urine: prior to sacrifice
- Metabolism cages used for collection of urine: No
- Animals fasted: No

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: once before first exposure and in forth week of exposure
- Dose groups that were examined: all animals
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Functional observation battery

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
No mortality and no clinically signs

BODY WEIGHT AND WEIGHT GAIN
no effects on body weight development

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
no effect on food consumption and/or water intake

FOOD EFFICIENCY
n.a.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
n.a.

OPHTHALMOSCOPIC EXAMINATION
no ophthalmoscopic findings

HAEMATOLOGY
no changes in haematological parameters

CLINICAL CHEMISTRY
all changes noted within range of historical controls

URINALYSIS
no changes in urinary parameters

NEUROBEHAVIOUR
no effects in FOB parameters noted

ORGAN WEIGHTS
no treatment related changes in organ weights

GROSS PATHOLOGY
no macroscopic findings

HISTOPATHOLOGY: NON-NEOPLASTIC
no treatment or test substance related histopathological changes

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
n.a.

HISTORICAL CONTROL DATA (if applicable)
n.a.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 75 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the data of the present study, the no observed adverse effect level (NOAEL) of the test substance is equal or greater 75 mg/kg body weight per day.

Executive summary:

The test item was orally administered in graduated doses of 0, 12, 30 and 75 mg/kg body weight per day to 3 groups of male and female Wistar rats by oral gavage. One group receiving the vehicle sterile water served as control. The volume of application was 5 mL/kg body weight and the animals were dosed 7 days per week for a period of 28 days. No mortality and no clinical signs were recorded in any of the dose groups during the treatment period of this study. Additionally, no effects with clinical relevance were observed in any of the parameters of the functional battery testing and no ophthalmoscopic findings were noted. Body weight development and food intake were not affected. No relevant differences were found for haematological and blood coagulation parameters. Slight deviations in the clinical biochemistry parameters glucose, total protein, cholesterol and sodium in male or female treatment groups were within the range of historical controls. Additionally, deviation observed for relative weight (to terminal body weight) of kidney in female high dose group animals were not associated with histopathological findings and hence, were unlikely to be related to treatment. Based on the data generated the no observed adverse effect level (NOAEL) of Genamin CH 020 is considered to be equal or greater 75 mg/kg body weight per day.