Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Limited reporting of study design and results. Purity and composition of test substance not explicit stated. Only one dose level used, without controls.

Data source

Reference
Reference Type:
publication
Title:
Toxicity of sodium chlorate to the dog
Author:
Heywood R, Sortwell RJ, Kelly PJ, Street AE
Year:
1972
Bibliographic source:
Vet Rec.90(15):416-418

Materials and methods

Principles of method if other than guideline:
Method: other
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Test substance: other TS: commercial preparation marketed as a weed killer.
- Physical state: Powdered Sodium chlorate marketed as weed killer.

Test animals

Species:
dog
Strain:
Beagle
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Pedigree Beagle Dog
- Age at study initiation: no info
- Weight at study initiation: females 9.2 - 11.75 kg; males 10.95 - 15.0 kg

Administration / exposure

Route of administration:
other: stomach-tube
Vehicle:
water
Details on exposure:
Total volume applied: 50 ml/day
Doses: 3 gram (50 ml, 60 g/L)
Duration of treatment / exposure:
5 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
200-326 mg/kg/day (50 ml of 6 % w/v solution)
No. of animals per sex per dose:
4 male, 4 female
Control animals:
other: no data specified
Details on study design:
Post-exposure period: for 4 of 8 animals: 7 days

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations included: mortality


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: frequency not indicated


BODY WEIGHT: Yes
- Time schedule for examinations: frequency not indicated


FOOD CONSUMPTION: not indicated


FOOD EFFICIENCY: not indicated


WATER CONSUMPTION: not indicated


OPHTHALMOSCOPIC EXAMINATION: no data


HAEMATOLOGY: Yes
- Time schedule for collection of blood: pre-dose, after 5 days, after recovery period
- Parameters examined: haemogram (PCV, RBC, TReticulocytes, WBC) blood urea, Hb and Met-Hb


CLINICAL CHEMISTRY: Yes


URINALYSIS: Yes
- Parameters examined: protein, total reducing substances, glucose, ketones, bile pigments and salts


NEUROBEHAVIOURAL EXAMINATION: no data
Sacrifice and pathology:
- Macroscopic: yes
- Microscopic: yes
Other examinations:
no
Statistics:
no

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not specified
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:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
CLINICAL SIGNS AND MORTALITY
- Mortality and time to death: 1/8, after 4 days dosing, (one female (308 mg/kgbw/d) after 4 days).
- Clinical signs: Two animals that received dosages > 300 mg/kg/day produced marked clinical symptoms (loss apetite, loss body weight, vomiting and blood streaked faeces, and blood in urine). Other 6 animals showed no clinical symptoms besides slight body weight loss in three animals.

BODY WEIGHT AND WEIGHT GAIN
- Body weight gain: not listed

FOOD CONSUMPTION / WATER CONSUMPTION
- Food/water consumption: not listed

OPHTHALMOSCOPIC EXAMINATION
- Ophthalmoscopic examination: no

HAEMATOLOGY
- Haematology: Red blood cell values reduced (PCV, Hb, RBC); reticulocytes increased

CLINICAL CHEMISTRY
- Clinical chemistry: Increase plasma urea level which returned to normal during recovery period. Only the animal that died showed elevated Met-Hb.

URINALYSIS
- Urinalysis: All free from protein, total reducing substances, glucose, ketones, bile pigments and salts.

NEUROBEHAVIOUR
-

ORGAN WEIGHTS
- Organ weights: no information

GROSS PATHOLOGY
- Gross pathology: Bluish coloured kidneys in both animals that received > 300 mg/kg, and clotted blood in bladder in the animal that died. No significant findings in other animals.

HISTOPATHOLOGY: NON-NEOPLASTIC
- Histopathology: haematopoeitic activity in spleen (3/8) and dark pigment in liver Kupffer cells (3/8). Haematogenous casts in kidney tubules in animal that died.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
-

HISTORICAL CONTROL DATA (if applicable)
-

IN GENERAL:
Two animals that received dosages > 300 mg/kg/day produced marked clinical symptoms and haematological and biochemical changes; One of them died after 4 days dosing. Other animals showed no clinical signs, and revealed no significant macroscopic post-mortem findings. Pathological findings were limited to changes indicative of haemolysis (pigmented Kupffer cells liver) and extra medullar haematopoeisis in spleen in some dogs. Red blood cell values were reduced, and reticulocyte counts increased. Plasma urea levels were increased, and returned to normal during recovery period. Only the animal that died showed elevated Met-Hb.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
< 200
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
200 other: mg/kg
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: males: 200 – 274 mg/kgbw/d; females 255-326 mg/kgbw/d.

Applicant's summary and conclusion

Conclusions:
Doses of 200 mg Sodium chlorate/kg/day in dogs seem to be a well tolerated dose level.