Sorbitan stearate

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given (no data on test substance purity).

Data source

Reference

Reference Type:

publication

Title:

The effect of emulsifying agents (tween 60 and span 60) on the gastrointestinal tract

Author:

Steigmann, F. et al.

Year:

1954

Bibliographic source:

Am J Dig Dis 20/12: 380-384

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

repeated dose toxicity: oral

Principles of method if other than guideline:

The study was undertaken to determine the effect of 2 emulsifying agents, Span 60 (the test substance) and Tween 60, in doses of 6 g/person/day for 28 days on changes in the gas pattern of the bowel, intestinal motility and gallbladder function as well as subjective symptoms.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sorbitan stearate

EC Number:

215-664-9

EC Name:

Sorbitan stearate

Cas Number:

1338-41-6

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

1,4-anhydro-6-O-stearoyl-D-glucitol

Details on test material:

- Name of test material (as cited in study report): sorbitan monostearate (span 60)

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 9
- Known diseases: Patients were examined to exclude gastrointestinal diseases. Furthermore, a complete physical examination and battery of laboratory tests on urinalysis, hemogram and chemical parameters (non-protein nitrogen, creatinine, blood urea nitrogen, total protein, albumin, globulin, alkaline phosphatase, cholesterol, cholesterol esters, thymol turbidity, gamma globulin and bromsulphalein retention) was performed and any patient showing significant abnormal laboratory findings was eliminated. Patients with gross abnormalities demonstrable by roentgenologic studies including flat plate, barium meal without fluoroscopy and cholecystography were also eliminated.
- Other: Subjects for the study, that appeared willing and able to cooperate, were choosen fom patients at the Oak Forest Infirmary, Oak Forest, Illinois, USA. These patients were institutionalised because of their degenerative diseases and belonged therefore mainly to the older age groups.

Route of exposure:

oral

Reason of exposure:

intentional

Details on exposure:

Each subject was given 3 g of the test substance in a capsule twice daily by a nurse, who controlled the ingestion of the capsules (corresponding to 100 mg/kg bw, based on the assumption of an average body weight of 60 kg).

Examinations:

- Other: A 14x17" film of the abdomen was obtained by standard techniques at the beginning, middle and end of the medication period. The films were taken at these various times to check the amount of gas appearing in the abdomen.
Gallbladder visualisation was attempted by the technique of Graham-Cole. Following this test, patients received an iodine containing compound which is radiopaque in the evening prior to the examination. Then, the patient was fasted overnight and in the morning the concentration of the dye within the gallbladder was visualised by spot films of the gallbladder area. Following a fatty meal and 45 minutes later, another x-ray of the gallbladder area was taken. Emptying of the gallbladder was evaluated by reduction of the size of the gallbladder. Finally, the films were compared and checked for concentration and emptying of the gallbladder.
Regarding motility of the gut, the patients were given a pint of thin barium and standard x-ray films were obtained of the stomach and small intestines immediately after ingestion. Four films were taken: two of the anteroposterior and two oblique exposures. Six hours later, a 14x17" flat plate of the abdomen was obtained to determine the barium passage time to locate the position of the head of the barium column within the intestine. These studies were repeated after 28 days of medication. All films were interpreted with special regard to passage time, rate of emptying of stomach amount of gas and barium in the intestine and location of the head of the barium column.

Results and discussion

Results of examinations:

- Other: No change was noted in the gas pattern in seven patients. There appeared to be more and less gas at the end of the observation period in one other person. There were no changes in the gallbladder function in seven cases; the emptying time appeared better in one person, and the visualisation was fainter in a second one. The stomach appeared unchanged in six patients; in two patients, it emptied slower and in one case, faster after the medication period. The intestinal pattern was unchanged in eight patients. It appeared "more normal" in one patient at the final examination. The passage of the barium column was unchanged in five patients, it was slower in two and more rapid in two at the end of the test period.

Applicant's summary and conclusion

Conclusions:

Administration of 6 g (corresponding to 100 mg/kg bw, based on the assumption of an average body weight of 60 kg) of the test substance for 28 days to humans had no significant effect on the physiologic activity of the gastro-intestinal tract as measured by changes in the gas pattern of the bowel, by gastric emptying time, by passage of barium through the gastro-intestinal tract and by gallbladder visualisation.