Cyclohexanecarboxylic acid, 1-hydroxy-, ethyl ester

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Adequacy of study:

other information

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 407

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: rat, Wistar Hsd Cpb:WU

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: 2 % Cremophor EL (v/v)

Details on oral exposure:

Method of administration:
gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 40 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 40 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Neither daily in-cage observations, nor weekly clinical
examinations including observations in an open field
revealed treatment-related findings in any dose group.


Detailed behavioral investigations (functional obesrvational
battery, assessment of motor activity) gave no evidence for
a neurotoxic potential of the test substance.


Body weight development was not retarded by the treatment
with the test substance up to 1000 mg/kg.


Survival was not affected by the treatment with the test
substance. One female treated at 40 mg/kg/day died during
blood sampling procedure.

Laboratory findings:
The hematological investigations gave no indication of a
test substance related effect on parameters of red and white
blood or on blood coagulation.


Clinical laboratory tests (determination of enzyme
activities, concentrations of substrates and electrolytes in
peripheral blood) revealed no indication of a treatment-
related effect.


Urinalyses showed that in urine of all animals of the

1000 mg/kg group ketone bodies were present, the pH-value
was decreased and fatty droplets were observed in males.
Ketone bodies in the urine were also noted in 3/5 males at
40 mg/kg/d and in 4/5 males and 2/5 females at 200 mg/kg/d.


In the sediment of animals of the high dose group triple
phosphates were not present and bacteria were observed with
lower grading than in other groups or were absent. This was
not regarded as an adverse effect.

Effects in organs:
The ophthalmoscopic examinations afforded no evidence of
treament related effects on eyes.


In males and females of the 1000 mg/kg group an increase in
liver weights was observed. Histopathology revealed no
morphological changes in the liver.


At 200 mg/kg and above females revealed morphological
changes in epilethal cells of the proximal straight tubules
in the corticomedullary kidney region (P3 segment),
increased by incidence and severity. The epithelial cells
appeared to be flattened with a fringy brushborder and the
lumen was dilated. These findings are not regarded as a
damage of the kidneys as signs of cell degeneration or
necrosis were absent.


Gross and histopathological investigations of other organs
and tissues gave no indication of test-compound-related
findings.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Basis for effect level:

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

2

Dose descriptor:

NOEL

Effect level:

40 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:

Classified as: Not classified