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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted prior to the appropriate OECD TG and GLP. No sufficient information, including purity data is available for the test material and test animals as well as environmental conditions during the treatment period. Moreover, not all blood and clinical chemistry parameters as well as organ weights were determined. The number of control and treated animals is not available; only one dose was administered to the rats.

Data source

Reference
Reference Type:
publication
Title:
Stable aqueous solutions of antibiotics of the tetracycline group with improved tissue tolerance
Author:
Neumann, H., Viehmann, P.
Year:
1959

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The animals were administered with the test material at a single dose for 5 days/week. Moreover, only limited blood and clinical chemistry parameters as well as organ weights were determined. The number of control and treated animals is not available; only one dose was administered to the rats.
GLP compliance:
no
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
N-2-hydroxyethyllactamide
EC Number:
226-546-1
EC Name:
N-2-hydroxyethyllactamide
Cas Number:
5422-34-4
Molecular formula:
C5H11NO3
IUPAC Name:
N-2-hydroxyethyllactamide

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 90 - 120 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
physiological saline
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 450 mg/mL
- Amount of vehicle: 2 mL/kg bw
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
12 weeks
Frequency of treatment:
once daily, 5 days/week
Doses / concentrations
Dose / conc.:
900 mg/kg bw/day (nominal)
No. of animals per sex per dose:
No data
Control animals:
yes
Details on study design:
No data
Positive control:
Not applicable

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Body weight of the animals was recorded weekly during the course of the study.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Haematology was performed 8 and 12 weeks post-administration.
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters examined: Hemoglobin, total erythrocyte count, total leukocyte count

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Clinical chemistry was performed 8 and 12 weeks post-administration.
- Animals fasted: No data
- How many animals: No data
- Parameters examined: liver function via bromthalein test (quick test)

URINALYSIS: Yes
- Time schedule for collection of urine: Urinalysis was performed 8 and 12 weeks post-administration.
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: total protein, glucose, urinary sediment

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
HISTOPATHOLOGY: Yes (lung, liver, kidney, spleen, epididymides, ovaries, bone marrow, heart chamber)
Statistics:
Mean values and standard deviations were calculated where necessary.

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
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:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Details on results:
BODY WEIGHT AND WEIGHT GAIN: No significant body weight gain could be recorded in the treatment group compared to the control group.

HAEMATOLOGY: There were no treatment-related changes identified in the haematological parameters measured.

CLINICAL CHEMISTRY: There were no treatment-related changes identified in the clinical parameters measured.

URINALYSIS: Urinalysis did not reveal changes in the investigated urine parameters.

HISTOPATHOLOGY: NON-NEOPLASTIC: No treatment-related histopathological changes were detected.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 900 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No systemic effects could be observed during the course of the study.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Body weight gain after termination of the study (12 weeks)

Dose group (mg/kg bw/day)

Body weight gain (g)

0

93 ± 6

900

83 ± 7

Table 2: Haematology parameters

Dose group (mg/kg bw/day)

Hemoglobin (g%)

Leukocyte count (1000/mm³)

Erythrocyte count (10/mm³)

Quick test (sec)

0

14.6 ± 0.2

17.5 ± 1.6

7.8 ± 0.3

10.8 ± 0.3

900

15.3 ± 0.2

12.3 ± 0.9

8.3 ± 0.3

10.7 ± 0.3

Applicant's summary and conclusion