Registration Dossier

Diss Factsheets

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
Copper di-D-gluconate
EC Number:
208-408-2
EC Name:
Copper di-D-gluconate
Cas Number:
527-09-3
Molecular formula:
C12H22CuO14
IUPAC Name:
copper(2+) bis(2,3,4,5,6-pentahydroxyhexanoate)
Test material form:
solid
Specific details on test material used for the study:
The test substance was dissolved in tap water and administered in a single dose using a stomach cannula

Test animals

Species:
rat
Strain:
Wistar
Remarks:
SPF-quality, randomly bred
Sex:
not specified
Details on test animals or test system and environmental conditions:
Fourty young adult rats of the Wistar strain (SPF-quality, randomly bred) were obtained from the Broekman Institute, Someren, The Netherlands. Date of arrival at the animal house: 21-8-1984 (Dose range finding investigation) and 11-9-1984 and 18-9-1984 (Main study).
From that date on, the animals were individually housed in Macrolon cages. They had free access to tap water and standard laboratory animal diet (RMH-B, pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands. Four days before the start of the main study the animals were randomly distributed into 3 groups with approximately equal distribution of weights. At the start of the study the body weights of the males ranged from 263 to 351 g and those of the females from 174 to 202 g. The animal room temperature was maintained at 20 +-3°C and the relative humidity at 50 - 80 per cent. The artificial light sequence was 12 hours light, 12 hours dark. Feed was withheld overnight before dosing till 4 hours after administration of the test substance.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Based on the sponsor's acute toxicity data on related metal gluconates and literature data on copper salts a pilot study was performed in order to determine a dose range. Groups of one female and one male rat received a single oral dose of the test substance in tap water: 320, 560, 1000, 1800 and 3200 mg/kg body weight.
The dosage volume amounted to 10 ml/kg body weight. Both high dose animals (3200 mg/kg) and one female adminstered 1800 mg/kg died within approximately 24 hours of dosing.
The animals of the other treatment groups revealed no symptomsof systemic toxicity during the 7-day observation period.
Doses:
The following doses have been administered: 1800, 2400, 3200 mg/kg bw. The dosage volume amounted to 10 ml/kg bw.
No. of animals per sex per dose:
Groups of 5 male and 5 female
Control animals:
not specified

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 709 mg/kg bw
Remarks on result:
other: The LD50 value was calculated according to the 'maximum likelihood' method of Finney (reference 3).
Mortality:
All animals of the high dose group died within 24 hours of dosing. Eight out of ten animals of the medium dose group and five out of ten animals of the low dose group were found dead within 48 hours of administration of the test substance.
Clinical signs:
Most animals showed apathetic behaviour and reduced locomotive activity during a 4-hour period after dos ing. These symptoms did no longer appear in the surviving animals from day 4 of the observation period.
Body weight:
The individual body weights of the animals on the day of dosing (day 0) and weekly thereafter during their 14 days of observation are listed in Tables 1 and 2. Individual body weight and the day of death of animals found dead are presented in Tables 3 and 4.
Gross pathology:
Examination of the stomach from animals found dead revealed local haemorrhages (petechiae) and necrosis in the fundus. Moreover, the entire intestinal tract of these animals was congested. All surviving animals showed no treatment rel ated gross al terations during autopsy at the end of the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The calculated LD50 value for males and females together amounted to 1709 mg/kg body weight. Substance is classified as a Acute tox (Oral) 4.