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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well documented publication.

Data source

Reference
Reference Type:
publication
Title:
Methods of Therapy Employing Magensium Glucoheptonate
Author:
US Patent
Year:
1962
Bibliographic source:
Francesco Cipelli, Pavia, Italy, assignor to Merck & Co., Inc., Rahway, N.J., a corporation of New Jersey No Drawing. Filed June 2, 1961, Ser. N0. 114,333 3 Claims. (CL 167-55). Patented Nov, 13, 1962; 3,063,896.

Materials and methods

Principles of method if other than guideline:
Acute toxicity data on magnesium glucoheptonate are presented in the US patent relating to its use as pharmaceutical and for clinical employment in compositions and as a pharmaceutical carrier.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Magnesium glucoheptonate

Test animals

Species:
other: mouse and rat.
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: various routes of administration
Vehicle:
not specified
Doses:
No data
No. of animals per sex per dose:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
not specified
Dose descriptor:
LD50
Effect level:
21 260 mg/kg bw
Based on:
test mat.
Remarks on result:
other: for white mouse
Sex:
not specified
Dose descriptor:
LD50
Effect level:
18 170 mg/kg bw
Based on:
test mat.
Remarks on result:
other: for rats

Any other information on results incl. tables

Acute toxicity was studied in the white mouse, the rat, guinea pig, and rabbit. The LD50 was determined for various routes of administration. Since magnesium glucoheptonate was administered also by iv and ip routes to guinea pigs and rabbits, the results are not shown here as they are not relevant routes of exposure.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 values established for mice and rats exceed even 5000 mg/kg bw.
The conclusion on toxicity effects by the author: "Magnesium glucoheptonate has a very low acute tox icity. The chronic toxicity is also remarkably low and, indeed, with prolonged treatment, there is no noticeable toxic effect. Histological examination of animals after prolonged treatment shows normal internal organs. In traperitoneal treatment of pregnant rats during gestation has no effect on the normal birth of normal offspring".
Executive summary:

Acute toxicity data on magnesium glucoheptonate are presented in the US patent relating to its use as a new pharmaceutical. Acute oral toxicity is very low (LD50 of 21,260 and 18, 170 mg/kg bw were determined for white mouse and rat, respectively).

The invention of the patent also relates to a clinical employment of magnesioum glucoheptonate in compositions and as a pharmaceutical carrier. The invention relates also to a method of treating mammalian digestive tracts which comprises administering to said mammal at least 4.0 g. of magnesium glucoheptonate. This magnesium salt can be used as a cholecystokinetic and as a choleretic, as a laxative or purgative or for prophylactic treatment of dyspeptic con ditions tending toward constipation safely without side effects and with a great deal more acceptance by the patients than previous treatments heretofore known.

Magnesium glucoheptonate is now found to be a much more effective material in X-ray examination of gall bladders because it is much more acceptable to patients and is much more easily tolerated by the patient. Magnesium glucoheptonate induces increased bile flow by physiological means alone: contractions of the gall bladder indeed are accompanied by relaxation of the sphincter of Oddi. Further advantage of magnesium glucoheptonate is that it is a pleasant tasting material which, surprisingly, is usable as a laxative or as a purgative, since the drug is endowed with peristaltic exciting activity in proportion to the dose ad ministered. Only at the most severe doses and only occasionally does magnesium glucoheptonate cause any discomfort and then it is only very minor. Magne sium glucoheptonate also brings about an improvement in appetite ‘and a lessening of digestive dif?culties and feel ings of abdominal tension after meals.

The dosage of magnesium glucoheptonate must exceed 4 g. in order to obtain the beneficial therapeutic etfects. Normally, dosages of approximately 7.5 g., twice a day, are used in acute and chronic a?ection of the liver and biliary tracts, in hepatopancreatic dyspepsia and habitual or occasional constipation. The dosage of about 12.5 g. has a laxative effect, whereas a dosage of about 25 g. has a purgative one; in serial X-ray examination of the gall bladder are normally employed about 17.5 to 20 g. of magnesium glucoheptonate. The salt is usually ad ministered as a 50% solution in water. Thus, the usual dosage is either 15 or 50 cc. of a 50% solution.

In summary, the magnesium glucoheptonate has these pharmacological activities: - It induces an emptying of the gall bladder; - It increases the secretion of bile without changing its glycotamocholate concentration; - It relaxes the Oddi’s sphincter; - It increases the enterical peristalsis; - Magnesium glucoheptonate has a very low acute tox icity. The chronic toxicity is also remarkably low and, indeed, with prolonged treatment, there is no noticeable toxic effect. Histological examination of animals after prolonged treatment shows normal internal organs. In traperitoneal treatment of pregnant rats during gestation has no effect on the normal birth of normal offspring.