reaction product of 3,5-di-tert-butylsalicylic acid and zirconium oxychloride, dehydrated, basic Zr : DTBS = 1.0 : 1.0 to 1.0 : 1.5

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: 96/54/EG, B.7; OECD 407 (1995)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

other: rat, Crl:CD(SD) IGS BR

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

Method of administration:
Oral gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 15, 150, 400 mg/kg/day
Basis:

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 400 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 400 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
There were no deaths during the study.

Poor clinical condition, characterized mainly by abnormal
gait, loss of body tone and piloerection, was noted among
animals receiving 400 mg/kg bw/d during Week 1; with
piloerection also noted during the final two weeks of
treatment. In addition hair loss, occurring mainly among
animals receiving 400 mg/kg bw/d, was noted during the
treatment period.

During the first week of treatment, body weight gain was
significantly decreased (by approximately 40 %) and food
consumption was reduced by 26 % and 14 % in males and
females respectively, receiving 400 mg/kg bw/d, in
comparison with controls. Subsequently they were decreased
among males only receiving 150 or 400 mg/kg bw/d during
Weeks 2 to 4 of treatment.

The food conversion efficiencies for both sexes receiving
400 mg/kg bw/d and for males receiving 150 mg/kg bw/d were
slightly lower than their respective controls during the
four week treatment period.

No behavioral changes that were considered to be indicative
of neurotoxicity were observed.

Laboratory findings:
The hematology investigations did not reveal any findings
that were considered to be related to treatment.

The blood chemistry investigations revealed significantly
increased alanine amino-transferase levels among both sexes
receiving 400 mg/kg bw/d and in males receiving

150 mg/kg bw/d, together with aspartate amino-transferase
levels in both sexes receiving 400 mg/kg bw/d. Significantly
higher total cholesterol levels, which followed a dosage
related trend, were noted among all treated female groups.
In addition slightly increased potassium values for both
sexes, urea levels in males and creatinine levels in females
were also noted for animals receiving 400 mg/kg bw/d.

Effects in organs:
Liver weights among females receiving 400 mg/kg bw/d were
statistically, significantly increased after adjustment for
terminal body weight, when compared with control.
Examination of all animals killed at the end of 4 weeks of
treatment revealed an increased incidence of hair loss in
both sexes and gaseous distension of the caecum in females,
among rats treated with 400 mg/kg bw/d, compared with none
in the controls.

The microscopic examination of animals killed after 4 weeks
of treatment, revealed no treatment related changes in the
tissues examined.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

15 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

15 mg/kg bw/day (nominal)

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:

Treatment at 15 mg/kg/day represents the NOAEL (however, findings not considered as being adverse, e.g. food consumption, body weight gains and blood chemistry parameters). In addition, no treatment related microscopical changes were observed among tretated animals and treatment at 150 and 400 mg/kg/day over the 4-wk treatment period. Thus classified as: NOT CLASSIFIED.