Benzoic acid, 3-(trifluoromethyl)-, methyl ester

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EEC Directive 96/54 B.7 (OECD 407)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

457-830-5

EC Name:

-

Cas Number:

2557-13-3

Molecular formula:

Hill formula: C9 H7 F3 O2

IUPAC Name:

Methyl, 3-Trifluoromethylbenzoate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

olive oil

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 100 mg/kg bw/day
Male: 5 animals at 300 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 100 mg/kg bw/day
Female: 5 animals at 300 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
No animal died during the study period.


1000 mg/kg body weight/day:

. Anogenital region smeared with urine, seen in 4 males and
5 females

. Piloerection obtained in 4 males and 4 females on several
days of the study, predominantly 3 to 4 hours after
substance administration

. Salivation slight to severe, observed in all males and
females beyond the first week ofmadministration until the
end of the study (before as well as up to 4 hours after treatment)

. Water consumption increased, statistically significant in
males on days 7, 14 and 28 and in females on days 7, 14 and 21

. Unsteady gait obtained in all males and females on day 22
and additionally in one animal of each sex on day 23

. Slight tremors in 2 males and stiff gait in 1 female
animal observed during functional observational battery,
additionally to the above-mentioned clinical findings

. Overall motor activity significantly reduced in males and
females (in addition several single intervals were reduced
in females)

. Increased alanine aminotransferase, alkaline phosphatase,
magnesium, urinary volume, abnormal urinary crystals and
renal tubular epithelial cells in both sexes

. Increased total bilirubin and triglycerides in females and
increased granular casts in males

. Decreased total protein and globulins in both sexes and
decreased albumin in males

. Increased absolute and relative liver weights in male and
female animals


300 mg/kg body weight/day:

. Salivation slight to moderate, observed in all males
beyond the first week of administration until the end of the
study (before as well as up to 4 hours after treatment)

. Slight salivation in 1 female animal observed during
functional observational battery

. Water consumption increased, statistically significant in
males on day 14


100 mg/kg body weight/day:

. No substance-related adverse findings

Laboratory findings:
There are no treatment-related changes in the hematological
parameters measured.

Effects in organs:
All findings noted were single observations either, or were
similarly in distribution pattern and severity in control
rats compared to treatment groups. All of them are
considered to be incidental and/or spontaneous in origin.

All findings noted were single observations either, or were
similarly in distribution pattern and severity in control
rats compared to treatment groups. All of them are
considered to be incidental and/or spontaneous in origin.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Basis for effect level:

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

2

Dose descriptor:

NOEL

Effect level:

100 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

Any other information on results incl. tables

Signs of general systemic toxicity as well as neurological effects could be determined at 1000 mg/kg body weight per day over a period of 4 weeks. Only minor effects were obtained in mid dose animals. Target Organs were liver and kidneys.

Under the conditions of the present study, the no observed adverse effect level (NOAEL) was 100 mg/kg body weight per day in both sexes.

Applicant's summary and conclusion

Conclusions:

signs of general systemic toxicity as well as neurological effects could be
determined at 1000 mg/kg body weight per day over a period of 4 weeks. Only minor
effects were obtained in mid dose animals. Target Organs were liver and kidneys.
Under the conditions of the present study, the no observed adverse effect level (NOAEL)
was 100 mg/kg body weight per day in both sexes.