Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: according to OECD 401, GLP lack of data on the purity / quality of the sample tested

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
Reference substance name:
The substance Citrowanil B M 2/585 Nr. 4 was a clear fluid in a brown glassbottle.
IUPAC Name:
The substance Citrowanil B M 2/585 Nr. 4 was a clear fluid in a brown glassbottle.
Details on test material:
Citrowanil B

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test animals: SPF-Wistar-rats (strain Winkelmann, Paderborn) with mean body weights of 180 - 200 g.
The animals were kept in randomised groups kept in single cages.
They were fed with a laboratory standard diet by Altromin (Lage, Germany) and watered ad libitum.
Temperature: 22 +/- 1 °C
relative humidity: 45 - 55 %
daily illumination: 12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
Group IV: undiluted
Details on oral exposure:
Oral administration by non-flexible stomach tube after starving 16 hours.
Doses:
Group I: 1 ml/kg BW = 965.7 mg/kg BW
Group II: 2 ml/kg BW = 1931.4 mg/kg BW
Group III: 3 ml/kg BW = 2897.1 mg/kg BW
Group IV: 5 ml/kg BW = 4828.5 mg/kg BW
No. of animals per sex per dose:
Group I and IV: 3
Group II and III: 5
Control animals:
no
Statistics:
Calculation of the LD 50 was made according to Lichfield & Wilcoxon

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2.2 mL/kg bw
Based on:
test mat.
95% CL:
2 - 2.5
Remarks on result:
other: Slope function S = 1.23 (1.13 - 1.34)
Mortality:
48 hours 7 days 14 days
Group I: 0/6 0/6 0/6
Group II: 2/10 (1 male and 1 female) 4/10 (3 male and 1 female) 4/10 (3 male and 1 female)
Group III: 4/10 (2 male and 2 female) 8/10 (4 male and 4 female) 8/10 (4 male and 4 female)
Group IV: 4/6 (1 male and 3 female) 6/6 6/6 (Last 2 male animals died within 96 hours.)

The 48 hours LD50 was found at 3.6 ml of the product per kg of body weigt.
Since some late mortalities did occur, the 14 days-LD50 is 2.2 ml/kg of body weight.
Clinical signs:
In all dosage groups the preparation caused 2 hours p.a. apathy, sedation, enforced respiration, abdominal ache, pinched eyes and diminished readines for reflexing. These symptoms continued up to 24 hours or caused mortalities. 4 out of 6 animals of the highest dosage group died within 24 hours. After 4 till 5 days all surviving animals except diminished weight gains in groups I - III did not show any remarkable symptoms. All animals of group IV showed coma after 3 hours and died within 4 days.
Body weight:
The surviving animals of dosage groups showed a clear reduced development of body weight; with increasing dosage animals gained less weight.
Details: see Table "Any other information".
Gross pathology:
Neither the acute mortalities nor the animals killed at the end of the test showed pathological changes in the cranium respectively in the thorax cavity. Intestinal in the acute mortalities slight hyperaemia was observed. These findings only did also occur in animals of final autopsy.

Any other information on results incl. tables

Development of Body Weights

Group Sex Starting Weight (g) 14 Days Body Weight (g)
I male 196.3 +/- 5.51 238.7 +/- 15.70
II male  197.0 +/- 4.53 220.5 +/- 19.50
III male 196.8 +/- 4.60 180.0 +/- -
 IV male  199.3 +/- 3.06   - -
       
I female 102.7 +/- 2.31 202.0 +/- 6.00
II female  193.2 +/- 2.59 193.3 +/- 11.00
III female 191.8 +/- 2.05 168.0 +/- -
 IV female  190.0 +/- 0.00   - -

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Considering the density of the test compound the LD 50 value is 2,024 mg/kg BW (> 2000 mg/kg BW, no classification) Criteria used for interpretation of results: OECD GHS
Conclusions:
This interpretation of results of the study does not confirm the classification according to Regulation (EC) No 1272/2008, Annex VI, Table 3.1 and 3.2.
Executive summary:

The product Citrowanil B M 2/585 Nr. 4 was tested in an acute toxicity study after one oral application at the dosages of 1, 2, 3 and 5 ml /kg body weight to the rat with a 14 day observation period according to OECD 401.

The following results were found:

The 48 hours LD50 was found at 3.6 ml of the product per kg of body weigt. Since some late mortalities did occur, the 14 days-LD50 is 2.2 ml/kg of body weight.

Considering the density of the test compound the LD 50 value is 2,024 mg/kg BW.

The slope function was measurable well (1.23).

The toxic symptomatic was marked by quick occuring abdominal ache syndrome, increased frequently of respiration, apathy, sedation and diminished readiness for reflexing. After few hours these symptoms changen from sedation to coma.

The surviving animals of dosage groups showed a clear reduced development of body weight; with increasing dosage animals gained less weight.

Macroscopical adspection during autopsy did not show alterations in the cases of acute mortalities and also not at final autopsy in the cranium and thorax. Intestinal was observed hyperemic small and large intestines in acute mortalities and at final autopsy only.