title: An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract.
abstract: A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. This study extends the observations in newborn baboons (McGill et al., 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1β, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.
authors.affiliation: TOXpertise, LLC, Princeton, NJ 08540, USA. Electronic address: myra@toxpertise.com.
authors.forename: M L
authors.initials: ML
authors.lastname: Weiner
authors.affiliation: Abbott Nutrition, Columbus, OH 43219, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Ferguson
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Thorsrud
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: K G
authors.initials: KG
authors.lastname: Nelson
authors.affiliation: Celtic Colloids Inc., Topsham, ME 04086, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Blakemore
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zeigler
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cameron
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: A
authors.initials: A
authors.lastname: Brant
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cochrane
authors.affiliation: MPI Research, Mattawan, MI 49071, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pellerin
authors.affiliation: Abbott Nutrition, Columbus, OH 43219, USA.
authors.forename: B
authors.initials: B
authors.lastname: Mahadevan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002351:Carrageenan / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects*; D007107:Immune System / Q000187:drug effects*; D041943:Infant Formula / Q000737:chemistry*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D013552:Swine; D018675:Toxicity Tests; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan
keywords: Carrageenan; Gastrointestinal tract; Immune system; Infant formula; Piglet