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October 18th, 2021

Laboratory animal data related to emulsifiers

Taken directly from Encyclopedia of Food Sciences and Nutrition

In Laboratory animals

In laboratory animals colonic damage can be induced experimentally by administration of therapeutic agents. Dogs administered 2.5 mg/kg of the non-steroidal, anti-inflammatory drug indomethecin orally each day for periods of up to 23 days developed not only gastric and small intestinal ulceration but also scattered hemorrhagic erosions in the colon

and rectum. Microscopically, these lesions were characterized by loss of superficial epithelial cells, mucus depletion of glandular epithelium and crypt abscesses, frequently with acute inflammation in adjacent lymphoid aggregates in the submucosa.

Another example of chemically induced colitis of relevance to the pathology of drug safety assessment is that induced by degraded carrageenans or synthetic sulfated dextrans. Carrageenans are a heterogeneous group of sulfated polysaccharides composed mainly of long chains of D-galactose subunits (D-galactan) derived from red seaweed species which are widely used as food emulsifiers, stabilizers, thickeners and gelling agents. When carrageenans are degraded by acid hydrolysis into smaller molecular weight fragments of about 20 to 40 kDa and administered orally in high doses (e.g. 10% of diet) to rats, mice, guinea pigs, rabbits and rhesus monkeys, colitis results.

Similarly, colitis has been induced in rats following administration of a 5% dietary admixture of dextran sulfatesodium, a sulfated polymer of glucose (α-D-glucose) of molecular weight of 54 kDa and a very high molecular weight D-glucan, amylopectin sulfate.

Although histological features of this form of induced colitis vary between study, species and strain, the colitis in rodents is generally characterized mucosal ulceration mainly in the cecum but also in the distal ileum, distal colon and rectum. There is mucus depletion with variable acute inflammatory infiltrate of the intact epithelium, increased cell proliferation, crypt abscesses and inflammatory infiltrate of the lamina propria with edema, hyperemia and even vascular thrombosis in the submucosa.

In the cecum of rats, ulcers are linear but often circulating the entire circumference of the intestinal wall with subsequent scarring and stricture formation. Ulcerating lesions in the rectum and at the anal margin are associated with squamous metaplasia. Both the squamous metaplasia and the regenerative hyperplasia of the columnar epithelium have been shown to progress even after cessation of treatment. Foamy macrophages containing metachromatic material, presumably polysaccharide, are also seen in the lamina propria, submucosa, regional lymph nodes, liver and spleen.

The precise mechanisms involved in the development of this colitis are unclear. Low dose levels, which may be expected to mimic human exposure, do not produce colitis. Dextrans, carrageenans and other polysaccharides of molecular weights outside the range 20 to 60 kDa tend not to incite colitis. An exception to this is the agent amylopectin sulfate, which has a far higher molecular weight. However, amylopectin is composed of polysaccharide chains which can be degraded by amylase, and therefore smaller molecular weight fragments may be formed in vivo. It has been suggested that colonic disease produced by these agents may be linked to induced changes in intestinal microflora or a result of increased intestinal permeability to antigenic or inflammatory substances normally resident in the large intestine.

Long-term administration of high doses of these agents to rats leads to the development of colorectal cancer despite their being devoid of mutagenic activity (see below). The only obvious pathological colonic changes associated with administration of these non-genotoxic agents are chronic inflammation and increased proliferative activity.

Lymphoid infiltrates without tissue damage were reported in the large bowel of rats treated with human recombinant interleukin 2. (Kinyanjui Encyclopedia of Food Sciences and Nutrition)


Dr. M


*****Chemical based emulsifiers in common household products are also of concern:

Visit the Environmental Working Group for safety data. Link
Dr. M







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