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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:
2016/07/08 - 2016/07/19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Remarks:
by National GLP compliance Monitoring Authority (NGCMA), Department of Science and Technology, Government of India
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide
EC Number:
946-272-2
Molecular formula:
Not specified (UVCB substance).Molecular formula of the main substance:C14Cu2H25Na1O17
IUPAC Name:
Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide
Test material form:
solid: granular
Details on test material:
Storage Temperature : Room temperature
Storage Container : Keep container tightly closed in a
cool and well ventilated place
Storage Location : Test Item Control Office, JRF

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation, India
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: Minimum: 173.2, Maximum: 192.5
- Fasting period before study: overnight
- Housing: Polypropylene rat cages covered with stainless steel grid top were used. Autoclaved clean rice husk was used as the bedding material.
- Diet: Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, U.S.A.
- Water: UV sterilized water filtered through Reverse Osmosis water filtration system.
- Acclimation period: 6 to 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23 °C
- Humidity (%): 57 to 66%
- Air changes (per hr): Minimum 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test item was found to be soluble in RO water, so the actual dose formulation was prepared using RO water as vehicle. Required quantity (2000 mg for set I, 300 mg for set II and set III) were mixed in RO water and the final volume was made up to 10 mL. Gavage solutions were prepared freshly prior to dosing on all the occasions.
Individual dose volume was adjusted according to body weight and dose level. All rats were dosed by oral gavage (day 0) using a BD 1 mL disposable syringe. Rats were fasted overnight prior to dosing and until three hours post-dosing.
Doses:
300 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
3 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing and observation: The rats were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Subsequently, the rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. The clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 0 and on days 7 and 14 and at death.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Remarks:
rat
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
All rats were found dead in set I treated with 2000 mg DABQUEL COMPLEX CuP/kg body weight. No mortality was observed in set II and III rats treated at the dose level of 300 mg DABQUEL COMPLEX CuP/kg body weight.
Clinical signs:
Clinical sign like lethargy was observed in rats treated with 2000 mg DABQUEL COMPLEX CuP/kg body weight while no clinical sign was observed in rats treated with 300 mg DABQUEL COMPLEX CuP/kg body weight.
Body weight:
Normal gain in body weight was observed in all the surviving rats.
Gross pathology:
External
External examination of found dead and terminally sacrificed rats did not reveal any abnormality.
Internal
Visceral examination of found dead rats revealed lesion such as congestion of liver (Rat N° 1, 2 and 3) whereas the terminally sacrificed rats did not reveal any lesion. Lesion observed in the found dead rats could be correlated with the test item used in the present study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LD50cut-off value) of DABQUEL COMPLEX CuP in Wistar rats was found to be 500 mg/kg body weight.
Executive summary:

In an acute oral toxicity study, three sets of fasted female Wistar rats (3 females/set) (10 to 11 weeks) were given a single oral dose of DABQUEL COMPLEX CuPat 2000 (for set I) and 300 [for set II and set III] mg/kg body weight and all the surviving rats were observed for 14 days.

Clinical sign like lethargy was observed in rats treated with 2000 mg DABQUEL COMPLEX CuP/kg body weight while no clinical sign was observed in rats treated with 300 mg DABQUEL COMPLEX CuP/kg body weight.

All rats were found dead in set I treated with 2000 mg DABQUEL COMPLEX CuP/kg body weight. No mortality was observed in set II and set III treated at the dose level of 300 mg DABQUEL COMPLEX CuP/kg body weight.

Normal gain in body weight was observed in all the surviving rats.

External examination of found dead and terminally sacrificed rats did not reveal any abnormality. Visceral examination of found dead rats revealed lesions such as congestion of liver (Rat N° 1, 2 and 3) whereas the terminally sacrificed rats did not reveal any lesion. Lesion observed in the found dead rats could be correlated with the test item used in the present study.

The acute oral median lethal dose (LD50cut-off value) of DABQUEL COMPLEX CuP in Wistar rats was found to be 500 mg/kg body weight.

Based on the results of this study, an indication of the classification for DABQUEL COMPLEX CuP is as follows:

Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2015): Category 4