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The SCID-hu mouse as a tool in immunotoxicological risk assessment: Effects of 2-acetyl-4(5)-tetrahydroxybutyl-imidazole (THI) and di-n-butyltin dichloride (DBTC) on the human thymus in SCID-hu mice

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Author: Heer, C. de · Schuurman, H.J. · Houben, G.F. · Pieters, R.H.H. · Penninks, A.H. · Loveren, H. van
Type:article
Date:1995
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Toxicology, 1-3, 100, 203-211
Identifier: 233014
doi: DOI:10.1016/0300-483X(95)03093-U
Keywords: Nutrition · Caramel colour III · Immunotoxicology · Organotins · Risk assessment · SCID-hu · Thymus · 2 acetyl 4 (1,2,3,4 tetrahydroxybutyl)imidazole · Dibutyltin dichloride · Food additive · Imidazole derivative · Animal experiment · Animal model · Animal tissue · Controlled study · Female · Histopathology · Immunotoxicity · Mouse · Nonhuman · Priority journal · Risk assessment · Thymus · Ammonia · Animal · Female · Food Coloring Agents · Human · Imidazoles · Immunosuppressive Agents · Mice · Mice, SCID · Organotin Compounds · Risk Assessment · Specific Pathogen-Free Organisms · Support, Non-U.S. Gov't · Teratogens · Thymus Gland · Animalia · Rodentia

Abstract

SCID mice engrafted with human fetal thymus and liver tissue fragments (SCID-hu mice) are currently considered as a new tool in human immunotoxicological risk assessment. Testing of various immunotoxicants exerting thymotoxicity via different intrathymic target cell types is necessary for validation of this model. Therefore, SCID-hu mice were exposed to 2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)-imidazole (THI), the immunotoxic component in the food additive, Caramel Colour III, or the organotin compound, di-n-butyltin dichloride (DBTC). Histopathological examination of the human thymus grafts of SCID-hu mice either exposed to THI or to DBTC showed a reduction in the relative size of the thymus cortex, an effect also described in rodents, These results indicate that the human thymus is a target for the immunotoxic action of both THI and DBTC. In addition, they indicate the promising potential of the SCID-hu mouse model as a tool for human immunotoxicological risk assessment.