Safety evaluation of a whey protein fraction containing a concentrated amount of naturally occurring TGF-β2.
TM0601p is a whey protein isolate derived from cow milk, containing a concentrated amount of transforming growth factor β2 (TGF-β2), and is intended for nutritional use in infants and adults. In vivo and in vitro studies have been performed to evaluate the safety of this product. In a 13-week toxicity study, treatment of adult Sprague-Dawley rats by gavage at up to 2000mg/kg/day did not result in any significant findings other than minor non-adverse changes in urinary parameters in females. The no-observed-adverse-effect level (NOAEL) was established as 2000mg/kg/day. In a juvenile toxicity study, rat pups received 600mg/kg/day by gavage from postnatal day (PND) 7 to PND 49. Transient lower bodyweight gain in the pre-weaning period was attributed to gastrointestinal effects of the viscous test material; following weaning, bodyweight gain was comparable to the vehicle controls. Reduced eosinophil counts and changes in urinary parameters (females) were recorded in treated pups at PND 49, and higher thymus weights were recorded in males only at the end of the recovery period (Day 77). None of the findings were considered adverse. There were no other significant findings and the NOAEL was established as 600mg/kg/day. No evidence of genotoxicity was seen in the bacterial reverse mutation test or the in vitro micronucleus test. Overall the results obtained present a reassuring safety profile for TM0601p.
CiToxLAB France, 27005 Evreux Cedex, France. Electronic address: roy.forster@fr.citoxlab.com.
Roy
R
Forster
Armor Protéines, Le Pont, 35460 Saint-Brice-en-Coglès, France. Electronic address: michel.bourtourault@armor-proteines.fr.
Michel
M
Bourtourault
Nestlé Research Center, Nestec, Vers-chez-les-Blanc, 1000 Lausanne, 26, Switzerland. Electronic address: YongJoo.Chung@rd.nestle.com.
Yong Joo
YJ
Chung
CiToxLAB France, 27005 Evreux Cedex, France. Electronic address: jeremy.silvano@fr.citoxlab.com.
Jérémy
J
Silvano
CiToxLAB France, 27005 Evreux Cedex, France. Electronic address: guillaume.sire@fr.citoxlab.com.
Guillaume
G
Sire
CiToxLAB France, 27005 Evreux Cedex, France. Electronic address: francois.spezia@fr.citoxlab.com.
François
F
Spezia
Armor Protéines, Le Pont, 35460 Saint-Brice-en-Coglès, France. Electronic address: caroline.puel@soredab.org.
Caroline
C
Puel
Lyon Poison Center, 162, Avenue Lacassagne, 69424 Lyon Cedex 03, France. Electronic address: descotes@me.com.
Jacques
J
Descotes
Armor Protéines, Le Pont, 35460 Saint-Brice-en-Coglès, France. Electronic address: takashi.mikogami@armor-proteines.fr.
Takashi
T
Mikogami
D000818:Animals; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests / Q000379:methods; D008894:Milk Proteins / Q000009:adverse effects*; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012449:Safety; D053781:Transforming Growth Factor beta2 / Q000009:adverse effects*; D015430:Weight Gain / Q000187:drug effects; D000067816:Whey Proteins
D008894:Milk Proteins; D053781:Transforming Growth Factor beta2; D000067816:Whey Proteins
TGF-β2; TM0601p; Transforming growth factor; Whey protein isolate