2-chloro-6-fluoro-phenol

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: Annex V.

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: Rat (wistar Crl:(WI) BR)

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

propylene glycol

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 50 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 500 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 500 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Mortality data:

There were no treatment-related deaths during the study. One
control female died during blood sampling on the final day
of the study.


Clinical observation:

There were no clinical signs of toxicity or behavioural
changes over the 28-day observation period that were
considered to be related to treatment.

Slight post-dosing salivation occurred in all males and
females of group 4 and one group 3 male in week 3 and/or
4.Incidental findings that were noted included alopecia,
rales, scabs and wounds.


Functional observation

No changes were observed in hearing ability, pupillary
reflex, static righting reflex and grip strength in the
animals treated, when compared with the performance of the
control animals. The variation in motor activity did not
indicate a relation with treatment.


Body weight

Females of group 4 (500 mg/kg) showed a reduced body weight
gain (by approximately 5%) during the final week of
treatment. Some individual body weight values of the treated
males were considered to be high when compared to those of
the control males, resulting in a statistically significant
increased (by approximately 9%) body weight gain for group 3
animals in week 3.

Laboratory findings:
Haematology:

There were no haematological or clinical chemistry changes
that could be considered toxicologically significant.


Clinical biochemistry:

Statisticaly significantly higher values were recorded for
patassium in males of group 4 (500 mg/kg).

Effects in organs:
Macroscopic examination:

Macroscopic observations at necropsy did not reveal any
alterations that were considered to have arisen as a result
of treatment.


Organ weights:

Higher mean absolute (26% increase) and relative (17%
increase) spleen weights were noted for males (26% increase)
recieving 500 mg/kg/day.


Microscopic examination:

There were treatment-related microscopic findings in the
forestomach at 500 mg/kg/day: minimal erosion (2/5 males)
and minimal epithelial hyperplasia (3/5 males and 2/5
females) of the forestomach.

Minimal/slight tubular atrophy was present in the testes of
a proportion of treated animals from all 3 dose groups
(50mg/kg/day and above).

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

< 50 mg/kg bw/day (nominal)

Basis for effect level:

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

2

Dose descriptor:

NOEL

Effect level:

50 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: Xn - harmful