Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Assessed after consultation with the relevant Authority. Data migrated from NONS files provided by Authority contain insufficient information.

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Report Date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Qualifier:
according to
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
GLP compliance:
yes
Remarks:
PHARMACO-LSR LTD. EYE, SUFFOLK IP23 7PX
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): BTN/A
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1.0% w/v methylcellulose in distilled water.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 40, 200, 1000 mg/kg bw
Basis:
no data
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
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:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS, BODY WEIGHT AND MORTALITY
No signs of reaction to BTN/A were observed in males treated at 1000 mg/kg/day, or in animals treated at 40 or 200 mg/kg/day. Four females receiving 1000 mg/kg/day died during the study; ante mortem signs included underactivity, reduced body temperature, thin and ungroomed appearance, bodyweight loss, hunched posture and loose faeces.


HAEMATOLOGY
Packed cell volume, haemoglobin concentration, mean cell volume and mean cell haemoglobin of male rats treated at 1000 mg/kg/day were marginally lower than those of the male controls. The neutrophil and eosinophil counts of one female surviving treatment at 1000 mg/kg/day were considerably higher than the counts recorded for the female control animals.


CLINICAL CHEMISTRY
Slightly low plasma alkaline phosphatase and slightly high alanine amino-transferase activities were recorded for rats treated at 1000 mg/kg/day, when compared with those of the control animals. The plasma albumin and total protein concentrations of male rats treated at 1000 mg/kg/day were marginally lower than those of the male controls. A reduced beta-globulin concentration and a correspondingly raised albumin: globulin ratio were recorded for the two surviving female rats treated at 1000 mg/kg/day.


URINALYSIS
Slightly lower urinary volume and pH, slightly higher specific gravity and protein concentration and increased epithelial cell populations for surviving female rats treated at 1000 mg/kg/day compared to the female controls. Slightly lower urinary pH was also recorded for male rats treated at this level,when compared with the male controls.


EFFECTS IN ORGANS and GROSS PATHOLOGY
There were no changes in the organs of animals surviving to termination which were attributed to BTN/A treatment.
Abnormal gastro-intestinal tract contents and emaciation were recorded for three of the four decedent females that received BTN/A at 1000 mg/kg/day: all four showed atrophy of the white pulp of the spleen and glycogen depletion of the liver. These non-specific findings were attributed to the poorconditions of the animals and not specifically to treatment with BTN/A.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (nominal)
Sex:
not specified
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Sex:
not specified
Basis for effect level:
other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
DSD: not classified
CLP: not classified