Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
repeated dose toxicity: oral
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Syloid HC was administered with the morning and evening feeding, starting with an oral dose of 1.0 gram per day that increased by 1.0 g daily up to a final, dose of 16 g/day. Syloid HC was given in two equally divided doses with the morning and evening feeding, to determine whether oral ingestion of silica hydrogel (Syloid 701) lowers significantly the levels of plasma total and low density (beta) lipoprotein (IDL) cholesterol in patients with primary type IIa hyperlipoproteinemia.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: nanoform, surface-treated
Specific details on test material used for the study:
Syloid HC (701)

Method

Type of population:
general
Subjects:
Six adult patients (three men and three nonpregnant women) with primary type Ila hyperlipoproteinemia (plasma LDL cholesterol level above age and sex specific 95th%; normal plasma total triglyceride level; no floating beta lipoproteins present from the Johns Hopkins Lipid Clinic were admitted to the Clinical Research Unit for three weeks. They were on no lipid-lowering or other medication for at least three weeks prior to admission.
Ethical approval:
not specified
Route of exposure:
oral
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
The short-term safety and efficacy of Syloid HC was studied in six adults (aged 20 to 51 years) with primary type II hyperlipoproteinemia. Three men and three women were admitted to a metabolic unit for three weeks. Four subjects were studied on a liquid formula diet containing 100 mg cholesterol/day and a ratio of polyunsaturated to saturated fat (P/S) of 1.0, while the other two were ingesting.a solid food diet containing 200 mg cholesterol/day a.hd a P/S of 2.0. Sufficient calories were provided to keep the weight constant {+ 1 kg). Syloid HC was administered with the morning and evening feeding, starting with an oral dose of 1.0 gram per day that increased by 1.0 g daily up to a final, dose of 16 gm/day. Syloid HC was given in two equally divided doses with the morning and evening feeding.
Examinations:
Specific Objectives
To determine whether oral ingestion of silica hydrogel (Syloid 701) lowers significantly the levels of plasma total and low density (beta) lipoprotein (IDL) cholesterol in patients with primary type IIa hyperlipoproteinemia.
2. To determine, through a dose-response study, the optimal dose of the silica hydrogel that lowers plasma total and LDL cholesterol.
3. To determine to what extent, if any, silica hydrogel is absorbed from the intestinal tract into the bloodstream.
4. To assess short-term clinical and chemical side effects of silica gel in these patients.
5. To determine the effect of silica gel on sterol metabolism; specifically, cholesterol synthesis and the excretion in the stool of neutral sterols and bile acids.

Results and discussion

Clinical signs:
In one subject, bile acid excretion increased somewhat but not markedly so.
Results of examinations:
No statistically significant effect of Syloid HC on the plasma levels of total cholesterol, low density (beta) lipoprotein.(LDL) cholesterol, high density (alpha) lipoprotein (HDL) cholesterol or total triglycerides was found. There was no significant increase in the serum or urinary levels of silica after Syloid HC administration.

Any other information on results incl. tables

As judged by clinical and chemical criteria, no significant adverse effects of Syloid HC were observed on hepatic or renal function. The number of white and red blood cells and platelets were unaffected. Two subjects had a fall in serum iron levels, one a fall in hemoglobin concentration, two had falls in carotene, one a fall in serum folate and another a fall in the vitamin A level. Clinical side effects include constipation in half the subjects, an unusual aftertaste in all 6, and one patient suffered gastritis.

Applicant's summary and conclusion

Conclusions:
In doses of up to 16 gm/day Syloid HC did not have a significant effect on the plasma lipid and lipoprotein levels in subjects with primary type II hyperlipoproteinemia. Although only slight untoward side effects were observed, however, at higher doses, Syloid HC is unpleasant to take and produces constipation.
Executive summary:

The short-term safety and efficacy of Syloid HC (a.k.a. Syloid 701) was studied in six adults with primary type II hyperlipoproteinemia.