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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study carried out in compliance with an internationally recognised guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Lot No: K1270019
Purity: 99.9%
Storage conditions: Room temperature

Test animals

Species:
rat
Strain:
other: Crl:CD (SD) albino
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: reputable supplier
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 224 to 262 g
- Fasting period before study: no
- Housing: solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fibre bedding.
- Diet (e.g. ad libitum): free access to a standard rodent diet
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes
- Acclimation period: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23C
- Humidity (%): 40 to 70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

IN-LIFE DATES: From: To: 7 February to 7 March 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10ml
- Justification for choice of vehicle: solubility

MAXIMUM DOSE VOLUME APPLIED: 10mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the dose levels for the study were chosen in compliance with the study guidelines. As no reliable previous toxicological information was available the initial dose level was 300 mg/kg.
Doses:
300 mg/kg and 2000mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical - twice daily; bodyweight - Days 1, 8, and 15
- Necropsy of survivors performed: yes


There were no deviations from protocol.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg one animal on Day 3 and one on Day 4. The test was terminated on Day 4 for the remaining animal on humane grounds.











Clinical signs:
There were no clinical signs of reaction to treatment seen in any animal dosed at 300 mg/kg throughout the study.

Prior to death - underactivity, hunched posture, tremors, partially closed eyelids and irregular breathing, vocalising in two animals, unsteady gait, increased body tone, reduced body temperature, loose faeces, fast breathing noted in one animal and thin build in one animal and salivation, piloerection and red coloured urine seen in one animal. All of these signs (except for salivation which was seen after dosing on Day 1) were seen from Day 3. No signs were observed for the animal which was found dead on Day 3.
Body weight:
A low bodyweight gain was noted on Day 15 for one animal. All other surviving animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of the decedents revealed congestion (characterised by darkened tissues/organs) of the subcutaneous tissue, heart and lungs, small (atrophy) spleen, stomach and caecum, pallor of kidneys and live, enlarge swollen stomach, gaseous distension of the caecum, brown yellow fluid content of the stomach, duodenum, small and large intestines, pale areas on the liver and kidneys.

At the macroscopic examination at study termination on Day 15 pallor and dark patches were seen on the lungs in one female dosed at 300 mg/kg, no abnormalities were noted in any of the remaining animals receiving 300 mg/kg.
Other findings:
- Other observations: a loss in bodyweight was noted for all decedents.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal oral dose (LD50) to rats of DMI was demonstrated to be between 300 and 2000 mg/kg bodyweight.