Summary of the In Utero/Postnatal Gavage Studies of AZT in C3B6.129F1-Trp53tm1Brd N12 Haploinsufficient Mice

MaleFemale
Doses in aqueous methylcellulose/Tween® 80 by gavage
30-Week Study a F0: 0 or 240 mg/kg per dayF0: 0 or 240 mg/kg per day
F1: 0 or 120/240 mg/kg per dayF1: 0 or 120/240 mg/kg per day
45-Week Study a F0: 0, 80, 160, or 240 mg/kg per dayF0: 0, 80, 160, or 240 mg/kg per day
F1: 0, 40/80, 80/160,F1: 0, 40/80, 80/160,
or 120/240 mg/kg per dayor 120/240 mg/kg per day
45-Week Stop-Study F0: 0 or 240 mg/kg per dayF0: 0 or 240 mg/kg per day
F1: 0 or 40 mg/kg per day postnatal days 1-8F1: 0 or 40 mg/kg per day postnatal days 1-8
Body weightsDosed groups less than 0 mg/kg groupsDosed groups less than 0 mg/kg groups, except in 45-week stop-study
Survival rates
30-Week Study 27/27, 21/2624/27, 26/26
45-Week Study 24/27, 21/27, 27/27, 22/2723/26, 23/27, 24/27, 21/27
45-Week Stop-Study 23/24, 22/2525/26, 23/26
Nonneoplastic effects
30-Week Study NoneNone
45-Week Study NoneNone
45-Week Stop-StudyNoneNone
Neoplastic effects
30-Week Study NoneNone
45-Week Study Liver: hepatocellular adenoma (3/26, 2/27, 6/27, 9/27)None
45-Week Stop-Study Liver: hepatocelluar adenoma (3/24, 5/25); hepatocellular adenoma or carcinoma (3/24, 7/25)None
Equivocal findings
30-Week Study Malignant lymphoma: (0/27, 3/26)None
45-Week Study NoneMalignant lymphoma: (0/26, 0/27, 1/27, 3/27)
45-Week Stop-Study NoneNone
Level of evidence of carcinogenic activityClear evidenceEquivocal evidence
Genetic toxicology
Micronucleated normochromatic erythrocytes and reticulocytes
30-Week Study Positive in males and females at 30 weeks of age
45-Week Study Positive in males and females at PND 1, PND 10, and PND 28
a

Pups in the 30- and 45-week studies were administered AZT doses that were half that of the maternal dose on post natal days 1 through 10. Pup doses were the same as maternal doses from post natal day 11 until the end of the studies.

From:

Cover of NTP Genetically Modified Model Report on the Toxicology and Carcinogenicity Studies of 3’-Azido-3’-Deoxythymidine (CASRN 30516-87-1) in Genetically Modified C3B6.129F1-Trp53tm1Brd N12 Haploinsufficient Mice (In Utero and Postnatal Gavage Study)
NTP Genetically Modified Model Report on the Toxicology and Carcinogenicity Studies of 3’-Azido-3’-Deoxythymidine (CASRN 30516-87-1) in Genetically Modified C3B6.129F1-Trp53tm1Brd N12 Haploinsufficient Mice (In Utero and Postnatal Gavage Study): NTP GMM 14 [Internet].
Leakey JEA, Allaben WT, Dunnick JK, et al.
Research Triangle Park (NC): National Toxicology Program; 2013 Oct.
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