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Toxicological information

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:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed GLP and OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
84/449/EEC
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 specifics: Hoe: WISKf (SPF71)
- Source: Hoechst AG breeding colony
- Weight at study initiation: male 180 g - 217 g (mean 193,5 g), female 176 g - 227 g (mean 202,5 g) on day 1 (treatment)
- Fasting period before study: approximately 16 hours before treatment, access to water permitted
- Housing: in groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard rat diet (Albtromin 1324)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Purity: Ph. Eur. III
- Concentration in vehicle: 25 % (w/v)
- Amount of vehicle (if gavage): 5.0 - 12.6 mL/kg body weight (test item in vehicle administered)
Doses:
As a result of preliminary studies the following doses were tested:
1250, 1600, 2000 and 3150 mg/kg body weight
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days starting with treatment day 0
- Frequency of observations and weighing:
mortality/viability: during the first 30 minutes and approximately 1, 2, 4 and 6 h after administration on day 0 and daily on days 1-14
clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 6 h after administration on day 0 and daily on days 1-14
body weights: on days 1 (prior to administration), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination
Statistics:
Probit analysis was applied to calculate LD50 of males, which was not possible for females due to the mortality ratio. LD50 values for males and females was within the same range, therefore LD50 for both sexes was calculated.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 600 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 890 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 870 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in the low dose groups. All animals (male and female) of the high dose group died. Details see table below.
Clinical signs:
The following symptoms were observed after application of the test substance: reduction of spontaneous activity, stupor, narcosis, flankes pinched in, squatting posture, prone position, ataxic gait, forward crawling, palpebr. fissure wide and narrow, coat bristling, increased lacrimation, twitching, no paw-reflex to pinching, no placing reflex, irregular respirate, panting, cyanosis.
In surviving animals symptoms were fully reversible after 1 day in males and after 4 days in females.
Body weight:
Increase of body weight was within the normal range for both sexes.
Gross pathology:
There were no macroscopic findings at scheduled necropsy of surviving animals.
Macroscopic findings of died males and females: transparent stomach lining, small intestine filled with brown-black mass, intestinal vessels injected, pancreas reddened, adrenal glands dark discoloured, liver partly light discoloured, lung grey-rose and filled with blood

Any other information on results incl. tables

Dose

Mortality

[mg/kg bw]

male

male [%]

female

female [%]

1 250

0 / 5

0

0 / 5

0

1 600

1 / 5

20

0 / 5

0

2 000

3 / 5

60

4 / 5

80

3 150

5 / 5

100

5 / 5

100

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
LD50, rat (male/female): 1870 mg/kg bw

Regulation (EC) No. 1272/2008: Acute toxicity category IV, H302
Directive 67/548/EEC: Harmful, R 22
Executive summary:

In a OECD guideline and GLP compliant study the LD50 of the test item for male and female rats was determined. Doses of 1250, 1600, 2000 and 3150 mg/kg body weight were administered to groups of 5 males and 5 females respectively. Probit analysis was applied to calculate LD50 for males, which was not possible for females due to the mortality ratio. LD50 values of males and females was within the same range, therefore LD50 for both sexes was calculated.

Numerous clinical signs were observed after application of the test substance: reduction of spontaneous activity, stupor, narcosis, flankes pinched in, squatting posture, prone position, ataxic gait, forward crawling, palpebr. fissure wide and narrow, coat bristling, increased lacrimation, twitching, no paw-reflex to pinching, no placing reflex, irregular respirate, panting, cyanosis. In surviving animals symptoms were fully reversible after 1 day (males) and after 4 days (females) respectively.

There were no macroscopic findings at scheduled necropsy of surviving animals. Macroscopic findings of died males and females: transparent stomach lining, small intestine filled with brown-black mass, intestinal vessels injected, pancreas reddened, adrenal glands dark discoloured, liver partly light discoloured, lung grey-rose and filled with blood.

LD50 (female): > 1600 - < 2000 mg/kg bw

The following LD50 values were calculated:

LD50 (male): 1890 mg/kg bw

LD50 (male/female): 1870 mg/kg bw

Based upon these findings the test substance has to be classified:

Regulation (EC) No. 1272/2008: Acute toxicity category IV, H302

Directive 67/548/EEC: Harmful, R 22