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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
other: non-standard (see below)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reasonably well documented study meeting generally accepted scientific principles but not conducted in compliance with GLP. Study acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Principles of method if other than guideline:
In a non-standard study, unspecified groups of rats were treated by gavage for 10 successive days with a further 10 days observation. Body weights were recorded prior to treatment and following the 5th and 10th administrations.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
No details given

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: unclear, possibly in "traganth suspension"
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
no details

VEHICLE
no details
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No details
Duration of treatment / exposure:
administration on 10 successive days.
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
doses 2, 4, 8, 16 g/kg bw/day
Basis:
no data
No. of animals per sex per dose:
not clear (based on data presented it is likely that the dose groups consisted of 10 rats).
Control animals:
other: control animals given 80 ml traganth suspension/kg bw (presumably per day). It is possible that this material was used as the vehicle. No further details presented.
Details on study design:
- Dose selection rationale: no details given
- Post-exposure recovery period in satellite groups: observation for 10 days following exposure.
Positive control:
No

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: observations reported as brief descriptions without reference to individual animals. No tabulated data presented.

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: prior to treatment and 24 h following the 5th and 10th daily administration

FOOD EFFICIENCY:
- Body weight gain: given as increase after 5 and 10 days' treatment. Pretreatment weights not given.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: No data
Other examinations:
None reported.
Statistics:
No details given

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
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:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
16 g/kg bw/day:sedation within 2 h of 1st treatment and death of all (of an unspecified number of) rats during 24 h following treament
8 g/kg bwlday: convulsions were reported (no further details) but no animals died during the 10 days of treatment or the 10 days observation that followed
4 g/kg bw/day: light sedation but no deaths
2 g/kg bw/day: no findings reported

BODY WEIGHT AND WEIGHT GAIN
Compared to a control group (80 ml traganth suspension/kg bw/day) body weight gain after 10 days treatment with 2, 4 or 8 g/kg bw/day, and 10 days observation, was unremarkable. (No statistics are given.)

OPHTHALMOSCOPIC EXAMINATION
Not applicable.

HAEMATOLOGY
Not applicable.

CLINICAL CHEMISTRY
Not applicable.

URINALYSIS
Not applicable.

NEUROBEHAVIOUR
Not applicable.

ORGAN WEIGHTS
Not applicable.

GROSS PATHOLOGY
Not applicable.

HISTOPATHOLOGY: NON-NEOPLASTIC
Not applicable.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not applicable.

HISTORICAL CONTROL DATA (if applicable)
Not applicable.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
8 000 mg/kg bw/day (actual dose received)
Sex:
not specified
Basis for effect level:
other: overall effects clinical signs; mortality; body weight
Dose descriptor:
LOAEL
Effect level:
16 000 mg/kg bw/day (actual dose received)
Sex:
not specified
Basis for effect level:
other: overall effects clinical signs; mortality; body weight

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Study design - Animal assignment

Test Group

Dose to Animal (mg/kg bw/day)

Control

80 ml/kg bw/day traganth suspension

1

2000 

2

4000

3

 8000

4

 16000

 

Table 2: Mortality and body weight gains during 10 days of treatment and 10 days of observation

Dose (g/kg bw/day)

Mortality%

(treatment day)

Mortality%

(observation days)

Total Weight Gain

(g)

1

2

3

4

5

6

7

8

9

10

1-10

Treatment day 5

Treatment day 10

Observation day 10

 0

 0

0

0

0

0

0

0

0

0

0

0

23.4

44.1

72.1 

2

 0

0

0

0

0

0

0

0

0

0

0

24.2

47.7

82.4

4

 0

0

0

0

0

0

0

0

0

0

0

23.1

43.6

 69.4

 8

 0

0

0

0

0

0

0

0

0

0

0

22.5

45.5

 81.5

 16

 100

100

100

100

100

100

100

100

100

100

100

-

-

 

Applicant's summary and conclusion

Conclusions:
A fairly limited report of a non-standard study, conducted without GLP compliance, identified 10-day NOAEL and LOAEL values in the rat of 8 and 16 g/kg bw/day, respectively. The 10-day LD50 was given as 11.3 (+/- 0.89) g/kg bw/day.