Fd Cosmet. Toxicol. Vol. 8, pp. 339-340. Pergamon Press 1970. Printed in Great Britain

SUMMARIES OF TOXICOLOGICAL DATA

LIFESPAN F E E D I N G STUDIES ON SORBITAN M O N O L A U R A T E A N D SORBITAN M O N O O L E A T E

(Summaries* of unpublished reports dated 18 January 1950 (SPAN 20) and 1 April 1950 (SPAN 80) of th.e Atlas Powder Company (now Atlas Chemical hTdustries, lnc.), Wilmington,

Delaware, USA)

Introduction

The sorbitan monolaurate used in these studies was manufactured by Atlas Powder Company (now Atlas Chemical Industries, Inc.), Wilmington, Delaware, USA, and is marketed under the trademark SPAN®20. Similarly, the sorbitan monooleate was made by Atlas and is marketed under the trademark SPAN®80.

These products find many applications as emulsifiers and surfactants, and are approved in the following countries for a variety of uses as direct and/or incidental additives to foods: Ecuador (Latin American Food Code), India, Italy, Japan, Netherlands, Norway, Panama, Peru, United Kingdom, United States, West Germany.

Tests on S P A N 20 sorbitan monolaurate

Acute oral toxicity

Ten male rats tolerated single oral doses of 20 g SPAN 20/kg without any apparent harm- ful effects during a 2-day observation period.

6-Wk feeding trial in rats

In a preliminary trial three groups of 12 male rats (50-70 g body weight) were given dietary levels of 0, 1 or 4 70 SPAN 20 for 6 wk. Test animals grew at a slightly slower rate than the controls. Haematological examination in one rat on 1 70 and two on 470 SPAN 20 after 6 wk of feeding revealed red and white blood-cell counts similar to those obtained in two controls. Histological studies on three rats/group showed no changes in the liver, kidneys, intestine, pancreas or bladder at 6 wk.

6-Wk feeding trial in monkeys

Two rhesus monkeys (2.25 and 2.85 kg body weight) were each given 2 g SPAN 20/day in food for 6 wk. No departure from normality was seen in the growth rate, the terminal red and white blood-cell counts or the histological appearance of the liver, kidneys and spleen.

*Prepared by BIBRA and published with the permission of Atlas Chemical Industries, Inc. ®SPAN is the trademark of Atlas Chemical Industries, Inc., Wilmington, Delaware.

339

340 SUMMARIES OF TOXICOLOGICAL DATA

Long-term feeding study in rats Dosage. Two groups of 50 and 30 male rats (body weight 54-63 g) were given dietary

levels of 0 or 5 ~o SPAN 20, respectively, for 2 yr. Growth. No growth retardation was observed at any period of the study in rats fed 5 ~o

SPAN 20. Haematology. No differences were seen in the haemoglobin concentrations and red and

white blood-cell counts of samples taken from one control and one test rat at 1 yr or in those from five controls and four test rats at 2 yr.

Clinical chemistry. Determinations of blood glucose and urea-nitrogen concentrations revealed no differences between survivors of control and test groups either at 1 or 2 yr. In addition serum cholesterol levels were found to be unaffected at 2 yr.

Mortality. After 1 yr 40 ~o of the rats of each group had died and after 2 yr only 15 ~ of both initial groups survived. None of the deaths could be attributed to treatment with SPAN 20.

Autopsy findings. The heart, lungs, spleen, liver, kidneys, thyroid and adrenals appeared to be of normal size in rats surviving for 2 yr. No gross or histological changes of significance were seen in the liver, kidney, brain, spleen, gastro-intestinal tract, pancreas, thyroid, parathyroid, prostate, pituitary, salivary or adrenal glands, urinary bladder, heart, lungs, testes, striated muscle or bone marrow in animals fed for 2 yr on 5 ~o SPAN 20.

Test on S P A N 80 sorbitan monooleate

Long-term feeding study in rats Dosage. Two groups of 50 and 30 male rats (body weight 54-63 g) were given dietary

levels of 0 and 5 ~ SPAN 80, respectively, for 2 yr. Growth. SPAN 80 had no adverse effect on growth rate at any period of the study. Haematology. No effect on haemoglobin concentration or on red and white blood-cell

counts was seen following determinations in two controls and one test rat at 6 months, on one control and one test rat at 12 and 17 months and finally in 13/50 and 5/30 control and test survivors, respectively, at 2 yr.

Clinical chemistry. Levels of blood urea at 6 months, blood urea and glucose at 12, 17 and 24 months and serum cholesterol at 24 months were within normal limits. The numbers of animals examined were the same as those used for the haematological studies.

Mortality. In the test groups consisting initially of 30 rats, 5, 14, 18 and 22 had died by 6, 12, 17 and 24 months, respectively, compared with 12, 22, 30 and 33 deaths by the same times in a group of 50 controls. No deaths were attributable to SPAN 80 treatment.

Autopsy findings. The heart, lungs, spleen, liver, kidneys, adrenals and thyroid were judged to be of normal size in animals fed 5 ~o SPAN 80 for 2 yr. Histological examination of the liver, kidneys and bone marrow of several test and control rats (as specified under Haematology) at 6, 12 or 17 months, revealed no significant lesions. Moreover neither gross nor histological changes were observed in the liver, kidneys, bone marrow, testes, striated muscle, prostate, gastro-intestinal tract, adrenals, pancreas, urinary bladder, spleen, lymph nodes, heart, salivary gland, lungs, brain, parathyroid and pituitary of survivors of 2-yr feeding of SPAN 80.

Conclusion

A dietary level of 5 ~o SPAN 20 or 80 fed to male rats for 2 yr had no adverse effect on growth, haematology, clinical chemistry, survival, organ size or histopathology.