α,α,α-trifluoro-4-nitro-m-cresol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-05-31 to 1990-09-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α-trifluoro-4-nitro-m-cresol

EC Number:

201-818-2

EC Name:

α,α,α-trifluoro-4-nitro-m-cresol

Cas Number:

88-30-2

Molecular formula:

C7H4F3NO3

IUPAC Name:

α,α,α-trifluoro-4-nitro-m-cresol

impurity 1

Reference substance name:

5-chloro-α,α,α-trifluoro-2-nitrotoluene

EC Number:

204-280-7

EC Name:

5-chloro-α,α,α-trifluoro-2-nitrotoluene

Cas Number:

118-83-2

Molecular formula:

C7H3ClF3NO2

IUPAC Name:

4-Chloro-1-nitro-2-(trifluoromethyl)benzene

impurity 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Dihydrogen oxide

impurity 3

Reference substance name:

3-Carboxy-4-nitrophenol

Cas Number:

610-37-7

Molecular formula:

C7H5NO5

IUPAC Name:

3-Carboxy-4-nitrophenol

Test material form:

liquid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

OTHER SPECIFICS: dark brown liquid

Test animals

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc.
- Age at study initiation: young adult, ~ 8 weeks
- Weight at study initiation: 200 - 300 g
- Fasting period before study: over night
- Housing: seperated by sex and group for the definitive portion of the study, individually for the range-finding portion of the study; in screen-bottom stainless stell cages.
- Diet: ad libitum, Rodent Chow #5001, Purina Mills
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1990-06-11 To: 1990-07-16

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 6.42 mL/kg bw
DOSAGE PREPARATION: The test material was dosed undiluted, using the bulk density to determine the dose volume and corrected for active ingredient (A.I.) (calculated dose/A.I. = dose to be administered). Individual doses were calculated based upon the animal´s body weight.
The test material was mixed with deionized water at a specific concentration for each dose level. Each test mixture was mixed during dosing to maintain a uniform suspension. Adjustments in the administered dose volume were made to account for the 77.9 % purity of the test material. An individual dose was calculated for each animal based upon its fasted body weight and administered by gavage using a dose volume of 6.42 mL/kg.

Doses:

50, 100, and 200 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 2.5, and 4 h after test substance administration and daily thereafter for at least 14 days for clinical signs and twice daily for mortality.
- Frequency of weighing: before study initiation, at day 7 and day 14 after test substance administration, and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The LD50 value for male, female and the sexes combined was determined by a computer program utilizing a modified Behrens-Reed-Muench Cumulant Method. No other statistical analyses were performed.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

160 mg/kg bw

Based on:

test mat.

95% CL:

> 95 - < 272

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

141 mg/kg bw

Based on:

test mat.

95% CL:

> 77 - < 259

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

151 mg/kg bw

Based on:

test mat.

95% CL:

> 102 - < 224

Mortality:

In the 50 mg/kg bw dose group, no mortality was observed. In the 100 mg/kg bw dose group, 1 out of 5 male and 2 out of 5 female animals died after test substance administration. In the 200 mg/kg bw dose group, 3 out of 5 male and 3 out of 5 female animals died after test substance administration.

Clinical signs:

other: All surviving animals appeard normal during the observation period of 14 days.

Gross pathology:

Yellowish-green semi-fluid material in the stomach of each animal and diffusely light yellow color of the mucosa. The cecum of males in the 50 mg/kg bw group had enlarged lumen. The observations were considered to be unrelated to the test material.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 of the test substance in rat was 141 mg/kg bw.

Executive summary:

In an acute oral toxicity study similar to OECD guideline 401, groups of 5/sex ~8 week old Charles River (Crl:CD°BR) rats were given a single oral dose of the test substance (50, 100, and 200 mg/kg bw) (Hazleton Laboratories, 1990). An observation period of 14 days followed administration. Weighing of the animals was performed before study initiation, at day 7, and at day 14 after test substance administration. Necropsy was performed on died and surviving animals.There were no treatment related clinical signs, necropsy findings or changes in body weight. An oral LD50 (based on ♀) of 141 mg/kg bw was determined.