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:
other: GLP Study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Cri:WI(Han) (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Number of animals: 18 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight: Young adult animals (approx. 8-11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark.
Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg (1 0 mL/kg) body weight.
300 mg/kg (1 0 mL/kg) body weight.
50 mg/kg (1 0 mL/kg) body weight.
5 mg/kg (10 mL/kg) body weight.
No. of animals per sex per dose:
18 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of
2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure
defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time
interval between the dose groups.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 - < 50 mg/kg bw
Mortality:
2000 mg/kg: 3/3
300 mg/kg: 3/3
50 mg/kg: 0/3
50 mg/kg: 2/3
5 mg/kg: 0/3
5 mg/kg: 0/3
The decedents at 2000 mg/kg were found dead within 1 minute post-treatment and the decedents at 300 mg/kg were found within 5 minutes post-treatment. The decedent and moribund animal at 50 mg/kg were found between days 2 and 4 post-treatment.
Clinical signs:
2000 mg/kg: No symptoms were noted in the time span of less than 1 minute between treatment and death.
300 mg/kg: Clonic spasms, hunched posture, uncoordinated movements, flat gait, quick breathing, salivation, moribund.
50 mg/kg: Lethargy, hunched or flat posture, uncoordinated movements, quick or slow breathing, shallow respiration, piloerection, salivation,
chromodacryorrhoea, leanness.
5 mg/kg: Hunched posture, piloerection
The surviving animals at 50 mg/kg had recovered from the symptoms between Days 6 and 14 and the animals at 5 mg/kg had recovered from the symptoms by Day 2.
Body weight:
One surviving animal at 50 mg/kg showed body weight loss in the first week post-treatment. Slight body weight loss or reduced body weight gain
in the second week post-treatment was observed in one surviving animal at 50 mg/kg and in all animals at 5 mg/kg. The body weight gain shown
by the remaining two surviving animals at 50 mg/kg over the study period was considered to be normal.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of DCM in female Wistar rats was established to be within the range of 5-50 mg/kg body weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to be 50 mg/kg body weight.
Based on these results:
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004), DCM should
be classified as: fatal if swallowed (Category 2) for acute toxicity by the oral route.
- according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/ EEC), DCM should be labelled as: toxic if swallowed (R25).