Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test substance was grounded into a fine powder.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Paderborn, Germany
- Weight at study initiation: 160 - 170 g
- Fasting period before study: 16 h
- Housing: Animals were housed individually during observation period
- Diet: Standard diet (tpf) Altromin, ad libitum
- Water: water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Tylose/Tween (1%)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6 - 12% (depending on test item concentration)
- Amount of vehicle: 1mL/100 g bw

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g bw
Doses:
600 (6% in vehicle), 756 (7.5% in vehicle), 953 (9.5% in vehicle) and 1200 (12% in vehicle) mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: at least after 1 and 24 h and 7 and 14 days after treatment (not further specified)
- Frequency of weighing: prior to testing and at the end of the observation period
- Necropsy of survivors performed: yes
Statistics:
Determination of LD50 values according to Litchfield & Wilcoxon and the Gaussian Integral

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
790 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
800 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was observed in males and females starting at concentrations of 756 and 600 mg/kg bw, respectively (for further details, please refer to Table 1).
Clinical signs:
600 mg/kg bw: listlessness, ataxia, lying on side, abdominal pain
756 mg/kg bw: sedation, exophthalmus, staggering, abdominal pain, straggly fur, soft faeces, significantly diminished reflexes
953 mg/kg bw: sedation, staggering, exophthalmus, abdominal pain, tremor, straggly fur, soft faeces, smeared and dirty body openings, significantly diminished reflexes
Body weight:
600, 756 and 953 mg/kg bw: slightly reduced body weight gain correlated to lower food intake
Gross pathology:
Surviving animals:
600 mg/kg bw: lobular pattern of the liver and gritty or mottled kidneys
756 mg/kg bw: hyperemia of stomach and small intestine, lobular pattern of the liver and gritty or mottled kidneys
953 mg/kg bw: hyperemia of small intestine, slight to pronounced lobular pattern of the liver and mottled or gritty kidneys
Other findings:
Macroscopic findings summarised for all groups:
stomach: light red to bloody-red (mucous membranes hyperaemised)
small/large intestine: light pink to bloody-red (mucous membranes hyperaemised)

Any other information on results incl. tables

Table 1 Results of Mortality

Dose Mortality
24 h
Mortality
7 d
Mortality
14 d
[mg/kg bw]
  N* N* N*
Males
600 0/10 0/10 0/10
756 2/10 3/10 3/10
953 8/10 9/10 9/10
1200 10/10 10/10 10/10
Females
600 0/10 1/10 1/10
756 3/10 3/10 3/10
953 7/10 9/10 9/10
1200 9/10 10/10 10/10

N* = number of animals

Table 2 Resulst of average body weight

Dose [mg/kg bw] Average starting body weight [g] Average body weight [g] after 14 days
600 165.2±4.54 202.1±9.46
756 165.2±4.21 192.6±19.16
953 163.8±3.74 175.0
1200 164.3±4.32 -

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Although the available data on acute oral toxicity meet the classification criteria for Acute toxicity Category 4, H302 according to Regulation (EC) No 1272/2008, the registrant follows the suggested classification defined in the RAC opinion for Acute toxicity Category 3, H301 according to Regulation (EC) No 1272/2008.