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: Study which meets basic scientific principles

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Cox CD
Sex:
male/female
Details on test animals and environmental conditions:
20 male and 20 female per group
Diet: ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: standard chow
Duration of treatment / exposure:
91 days
Frequency of treatment:
continuously
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20
Control animals:
yes, concurrent no treatment
Details on study design:
Post-exposure period: no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
FOOD EFFICIENCY: Yes
HISTOPATHOLOGY: Yes
HAEMATOLOGY: Yes
Sacrifice and pathology:
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
One rat escaped from its cage during the third week of the test and had to be eliminated because of contamination. One male from the mid-dose group and one female from the low-dose group displayed symptoms of inner ear infection.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
The only abnormality observed was a slightly elevated WBC in one animal. This change was not considered significant. All other values are within normal limits and there were no significant differences between treatment groups.
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There were no significant differences notes in organ to body weight ratios.
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
No lesions were found which followed a pattern of agent-induced toxicity. Tissue alterations observed were mild and were not considered significant.
Details on results:
AVERAGE BODY WEIGHT GAIN, FEED CONSUMPTION, AND EFFICIENCY
The only adverse significant differences noted were in body weight gain and feed efficiency in the female rats of the mid-dose group.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: no significant effects at highest dose tested

Target system / organ toxicity

Key result
Critical effects observed:
not specified

Any other information on results incl. tables

Bodyweight gain

 

males

females

Control

341±30

157±23

TEA-1 (250 mg/kg)

339±35

170±13

TEA-1 (500 mg/kg)

331±28

151±15

TEA-1 (1000 mg/kg)

329±32

161±22

 

Feed consumption

 

males

females

Control

2143±155

1542±105

TEA-1 (250 mg/kg)

2073±165

1592±108

TEA-1 (500 mg/kg)

2076±282

5166±115

TEA-1 (1000 mg/kg)

2091±155

1604±123

 

Feed efficiency

 

males

females

Control

15.95±0.98

10.18±1.1

TEA-1 (250 mg/kg)

16.35±0.97

10.72±0.67

TEA-1 (500 mg/kg)

15.56±0.84

8.62±2.7

TEA-1 (1000 mg/kg)

15.75±0.99

9.99±0.88

   

Organ to bodyweight ratio (LIVER)

 

males

females

Control

38.2±3.3

42.1±12.2

TEA-1 (250 mg/kg)

41.6±3.7

39.9±3.3

TEA-1 (500 mg/kg)

45.9±6.9

44.6±1.0

TEA-1 (1000 mg/kg)

49.6±2.9

45.3±2.9

 

Organ to bodyweight ratio (KIDNEY)

 

males

females

Control

7.6±0.6

8.1±0.3

TEA-1 (250 mg/kg)

9.3±1.3

10.2±1.4

TEA-1 (500 mg/kg)

9.2±0.7

11.1±0.7

TEA-1 (1000 mg/kg)

10.4±1.4

10.3±1.4

Applicant's summary and conclusion