Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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:
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 on until day 14 all of the animals were free of any clinical symptoms.

females:
- 3150 mg/kg bw: All of the tested animals were without any clinical symptoms for up to two hours after application. Between two and six hours all animals showed quiet behaviour. The skin of all animals was yellow-coloured starting two hours after application and lasting until day three. After one day there occured yellow-coloured faeces. From day four on until day 14 all of the animals were free of any clinical symptoms.
- 4000 mg/kg bw: All of the tested animals were without any clinical symptoms for up to two hours after application. Between two and six hours all animals showed quiet behaviour. The skin of all animals was yellow-coloured starting two hours after application and lasting until day three. After one day there occured yellow-coloured faeces. One out of the five tested animals showed still quiet behaviour and couched posture with spread legs after one day and also displayed ruffeled fur, convulsions, constricted palpebral fissures and a lowered respiratory rate. One animal died. From day four on until day 14 the remaining four animals were free of any clinical symptoms.
- 5000 mg/kg bw: All of the tested animals were without any clinical symptoms for up to one hour after application. Three animals died. From day eight on until day 14 the remaining two animals were free of any clinical symptoms.
Body weight:
no reduction of the body weight development
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.