Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-, N,N'-bis(phenyl and 2,4-xylyl) derivs.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 4 JULY 1983 to 1 AUG 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 401)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-N-phenylbutyramide]

EC Number:

228-787-8

EC Name:

2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-N-phenylbutyramide]

Cas Number:

6358-85-6

Molecular formula:

C32H26Cl2N6O4

IUPAC Name:

2,2'-[(3,3'-dichlorobiphenyl-4,4'-diyl)didiazene-2,1-diyl]bis(3-oxo-N-phenylbutanamide)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specification: Hoe: WISKf (SPF71)
- Source: Hoechst AG, Kastengrund, SPF-breeding
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: male mean: 187,2 g; female mean: 207,3 g
- Fasting period before study: 16 h
- Housing: 5 animals per Macrolon cage
- Diet: Altromin 1324 (Altromin-GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12,5% w/v

MAXIMUM DOSE VOLUME APPLIED: 40 ml/kg bw
Calculated dose volume was divided into two equal fractions and applied in a one hour interval.

DOSAGE PREPARATION: test substance was suspended in vehicle

Doses:

male: 5000 mg/kg bw
female: 5000, 4000, 3150 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 weighing: once per week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

Probit analysis: according to method of Lindner and Weber
95% confidence interval: according to method of Fieller and Sidak

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

2 228 mg/kg bw

Remarks on result:

other: The test item contained only 47% of the submission substance, i.e. LD 50 of 4740 mg test item / kg bw corresponds to 2228 mg submission substance/kg bw.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 350 mg/kg bw

Remarks on result:

other: No males died within the observation period. The test item contained only 47% of the submission substance, i.e. LD 50 of > 5000 mg test item / kg bw corresponds to 2350 mg submission substance/kg bw.

Mortality:

males: none of the tested animals died within the observation period
females:
- 5000 mg/kg bw: 3/5
- 4000 mg/kg bw: 1/5
- 3150 mg/kg bw: 0/5
The animals died within the first three days after application.

Clinical signs:

other: males: On the day of application the animals showed a reduced spontaneous activity, one male showed spread legs and three males a crouched posture. All animals had yellow-coloured faeces on day 1 and 2 and yellow coloured skin on days 1-3. From day four

Gross pathology:

male:
- 5000 mg/kg bw: no macroscopic anomalies found
female:
- 3150 mg/kg bw: no macroscopic anomalies found
- 4000 mg/kg bw: 4 animals had no macroscopic anomalies
The one animal which died during the test was eroded.
- 5000 mg/kg bw: 2 animals sacrificed at the end of the postexposure period had no macroscopic anomalies
3 animals died during the observation period:
- stomach was tightly filled with air and test substance
- intestinal tract was filled with test substance
- pancreas was rosy-coloured
- in two out of this three animals the lung and the adrenal gland were dark-coloured
- one out of the three animals displayed bright foci on the liver

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP regulation

Conclusions:

The testing for acute oral toxicity according OECD TG 401 yielded a median lethal dose (LD50) of 4740 mg test item/kg bw (corresponding to 2228 mg P.Y. 12/kg bw) in female Wistar-rats. The testing in male rats revealed no obvious toxicity in the tested dose, thus leading to a LD50 > 5000 mg/kg bw (corresponding to > 2350 mg Permanent-Gelb DHG/kg bw).
The test was performed with Permanent-Gelb DHG-80 which contains relevant amounts of Permanent-Gelb DHG, which is identical to the submission substance. Therefore the test results are considered adequate to fulfill the endpoint requirements.

Executive summary:

Acute oral toxicity of the test item was tested in male and female Wistar rats according to OECD TG 401. Administered dose levels were 3150, 4000 and 5000 mg/kg bw in female and 5000 mg/kg bw in male rats. Three females in the highest dose level and one female in the middle dose level died within 3 days after application. An oral LD50 of 4740 mg test item/kg bw (corresponding to 2228 mg P.Y. 12/kg bw) has been calculated. No lethality was observed in male rats.

Therefore, the test item has not to be classified for acute toxicity according to Regulation (EC) No 1272/2008.