α,α,α-trifluoro-4-nitro-m-cresol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-03-16 to 1994-04-04

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:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987-02-24

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992-07-31

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:

SOURCE OF TEST MATERIAL
- Batch No. of test material: C02910506
- Expiration date of the batch: 1995-02

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, in the dark, under fume cupboard

Test animals

Species:

rat

Strain:

Wistar

Remarks:

WISKf (SPD71)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund SPF breeding colony
- Age at study initiation: ♂ ~7 weeks, ♀ ~9 weeks
- Weight at study initiation: ♂ ~191 g, ♀ ~213 g
- Diet: ad libitum, Altromin 1324 rat diet
- Water: ad libitum, tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal skin
- coverage: ~30 cm²
- Type of wrap if used: Fixomull and Elastoplast

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with warm water
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

315, 400, and 500 mg/kg bw

No. of animals per sex per dose:

5 ♀, 5 ♂ (only at 400 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice every day for clinical symptoms and mortality (on weekends and on national holidays only once), weighing on day 8 and day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

The LD50 was established in female animals on the basis of the lethality rates by probit analysis (method of Fieller and Sidak, programs supplied by Pharma research and Development Informatics, HOECHST AG).

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

265.5 mg/kg bw

Based on:

act. ingr.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

409.1 mg/kg bw

Based on:

test mat.

Remarks on result:

other: based on the 64.9 % solution of the test substance

Mortality:

♀: In the 315 mg/kg bw dose group 1 out of 5 animals died. In the 400 mg/kg bw dose group 2 out of 5 animals died. In the 500 mg/kg bw dose group 4 out of 5 animals died.
♂: In the 400 mg/kg bw dose group 2 out of 5 animals died.

Clinical signs:

other: Decreased spontaneous activity, silted gait, irregular respiration, and tonoclonic convulsion. Additionally in the 400 and 500 mg/kg bw dose group squatting posture and prone position. Two days after application all clinical signs were reversible.

Gross pathology:

Animals died during the observation period showed light discolorations and demarcation of the liver. Surviving animals showed no macroscopically visible changes.

Any other information on results incl. tables

The skin of the animals showed erythrema, yellow discoloratios and indurations. Furthermore, scabbed skin, coarse or fine scales, desquamations of coarse or fine scales and parchment-like skin surface. Scar formation occurred in all dose groups at the treated skin areas.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 of the test substance in rat was 265.4 mg/kg bw, based on the 64.9 % solution of the test substance.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, groups of 7 - 9 week old Wistar (WISKf (SPD71) rats (5♀/dose, 5 ♂ at 400 mg/kg bw) were dermally exposed to the test substance for 24 hours to 10 % (6 x 5 cm) skin surface at doses of 315, 400, and 500 mg/kg bw (Hoechst AG, 1994). Animals then were observed for 14 days. Following clinical signs were observed: decreased spontaneous activity, silted gait, irregular respiration, and tonoclonic convulsion. Additionally in the 400 and 500 mg/kg bw dose group, squatting posture and prone position. Two days after application all clinical signs were reversible. No abnormalities were observed at necroscopy. A dermal LD50 of 409.1 mg/kg bw was determined. A LD50 of 265.5 mg/kg bw of the active ingredient based on the 64.9 % solution of the test substance was determined.