PMID- 22855551
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20131121
IS  - 1092-874X (Electronic)
IS  - 1091-5818 (Linking)
VI  - 31
IP  - 4
DP  - 2012 Jul-Aug
TI  - Investigation of the skin sensitizing properties of 5 osmolytic prodrugs in a 
      weight-of-evidence assessment, employing in silico, in vivo, and read across 
      analyses.
PG  - 358-63
LID - 10.1177/1091581812449662 [doi]
AB  - The amino acid esters ethyl glycinate (EG), DL-alpha-tocopheryl-(mono-)betainate 
      hydrochloride (TMB), DL-alpha-tocopheryl-(mono-)glycinate hydrochloride (TMG), 
      DL-alpha-tocopheryl-(mono-)prolinate hydrochloride (TMP), and 
      DL-alpha-tocopheryl-(mono-)sarcosinate hydrochloride (TMS) were previously shown to 
      exert an osmoprotective function to human skin in vitro. Based on literature 
      data, the parent compounds alpha-tocopherol (vitamin E) and the amino acids glycine, 
      betaine (trimethylated glycine), proline, and sarcosine (N-methylated glycine) 
      are not considered to be sensitizers. To investigate skin sensitizing properties 
      of the esters, EG, TMG, and TMP were tested in the Local Lymph Node Assay (LLNA). 
      Remaining esters were assessed by read across analysis considering structural 
      similarities and mechanistic aspects. The LLNA results were consistent with in 
      silico outcomes from ToxTree 2.5.0 indicative for protein binding; EG was 
      negative; TMG and TMP were positive. Since TMB and TMS showed structural 
      similarities to TMG and TMP and were also positive in ToxTree, it was concluded 
      that both TMB and TMS can also be expected to have a skin sensitizing potential 
      and therefore animal testing was waived.
FAU - Scheel, Julia
AU  - Scheel J
AD  - Department of Toxicology, Henkel AG & Co. KGaA, Duesseldorf, Germany. 
      julia.scheel@henkel.com
FAU - Keller, Detlef
AU  - Keller D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Toxicol
JT  - International journal of toxicology
JID - 9708436
RN  - 0 (Prodrugs)
RN  - 3SCV180C9W (Betaine)
RN  - 459-73-4 (glycine ethyl ester)
RN  - 9DLQ4CIU6V (Proline)
RN  - H4N855PNZ1 (alpha-Tocopherol)
RN  - TE7660XO1C (Glycine)
RN  - Z711V88R5F (Sarcosine)
SB  - IM
MH  - Animals
MH  - Betaine/pharmacology
MH  - Dermatitis, Allergic Contact/etiology/*physiopathology
MH  - Female
MH  - Glycine/*analogs & derivatives/pharmacology
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Osmosis/*drug effects
MH  - Prodrugs/*pharmacology
MH  - Proline/pharmacology
MH  - Sarcosine/pharmacology
MH  - Skin/*drug effects/metabolism
MH  - alpha-Tocopherol/*analogs & derivatives/pharmacology
EDAT- 2012/08/03 06:00
MHDA- 2012/12/14 06:00
CRDT- 2012/08/03 06:00
PHST- 2012/08/03 06:00 [entrez]
PHST- 2012/08/03 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
AID - 31/4/358 [pii]
AID - 10.1177/1091581812449662 [doi]
PST - ppublish
SO  - Int J Toxicol. 2012 Jul-Aug;31(4):358-63. doi: 10.1177/1091581812449662.