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Acute Toxicity: oral

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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:
guideline study
Remarks:
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

Constituent 1
Chemical structure
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'-dichloro-4'-{2-[2-oxo-1-(phenylcarbamoyl)propyl]diazen-1-yl}-[1,1'-biphenyl]-4-yl)diazen-1-yl]-3-oxo-N-phenylbutanamide
Test material form:
solid: nanoform

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 levelsopen allclose all
Key result
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.
Key result
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:
GHS criteria not met
Remarks:
Regulation (EC) no 1272/2008
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.