National Toxicology Program

CASRN: 30516-87-1

Formula: C10-H13-N5-O4

Synonyms/Common Names:

• AZIDOTYMIDINE
• AZT (AIDS INITIATIVE)
• RETROVIR
• ZIDOVUDINE

Known Uses:

PYRIMIDINE NUCLEOSIDE ANALOG WITH ANTIVIRAL ACTIVITY USED IN THE TREATMENT OF AIDS (MERCK 1989)

Short-Term Toxicity

• 9-Month (Gavage)  (C20310D) On Test 
  • Mice: P53 +/- (FVB/N)
  • Dose: AZT/3TC: 0, 240, OR 150 MG/KG BW/DAY -- AZT/3TC/NVP COMBO FOR P53 MICE: AZT: 0, 80, 160, OR 240 MG/KG BW/DAY; 3TC: 0, 50, 100, OR 150 MG/KG BW/DAY; NVP1-3: 0, 56, 112, OR 168 MG/KG BW/DAY; 1/8 DOSE NVP PND 1-3 AND 1/2 DOSE NVP PND 4-10
• 13-WEEK (Gavage)  (C88072) Completed 
  • NTIS No. PB99-145807  (Peer Review 12/11/1996)
    Citation: Toxicology and Carcinogenesis Studies of AZT (CAS No. 30516-87-1) and AZT/ a-Interferon A/D B6C3F1 Mice (Gavage Studies)
  • Rats: F344/N; Mice: B6C3F1
  • Dose: DOSES GIVEN twice a day AT 9AM & 3PM--R: 0, 125, 250, 500, OR 1000; M: 0, 25, 50, 100, 400, OR 1000 MG/KG

Long-Term Carcinogenicity

• 2-YEAR (Gavage)  (C20309) Histopathology 
  • Mice: B6C3F1; Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-)
  • Dose: DOSED: GD 12-18 -- 1) AZT 80 mg/kg + 3TC 40 mg/kg (loaded 4); 2) AZT 160 mg/kg + 3TC 80 mg/kg (loaded 4); 3) AZT 240 mg/kg + 3TC 120 mg/kg + 168 mg/kg NVP (loaded 12); 4) AZT 80 mg/kg + 3TC 40 mg/kg + 336 mg/kg NVP (loaded 12); 5) AZT 160 mg/kg + 3TC 80 mg/kg + 672 mg/kg NVP (loaded 36); 6) Controls (loaded 36)
• 9-MONTH (Gavage)  (C20310C) Histopathology 
  • Mice: C3B6F1-+/TRP53<TM1BRD>; Mice: C3B6F1-+/TRP53<TM1BRD>
  • Dose: 0, 80, 160, OR 240 MG/KG BW (GD 12-18 -- AZT ONLY); 0, 40, 80, OR 120 MG/KG BW (PND 1-10); 0, 80, 160, OR 240 MG/KG BW (PND 11-9 MO)
• 2-YEAR (Gavage)  (C88072) Report Complete 
  • TR-469 (NTIS No. PB99-145807)  (Peer Review 12/11/1996)
    Toxicology and Carcinogenesis Studies of AZT (CAS No. 30516-87-1) and AZT/ a-Interferon A/D B6C3F1 Mice (Gavage Studies)
  • Mice: B6C3F1
  • Carcinogenesis Results
  • Male Mice Equivocal Evidence 
  • Female Mice Clear Evidence 
  • Dose: MICE ONLY: 0, 30, 60, OR 120 MG/KG; 50/SEX

Genetic Toxicology

• In Vitro Cytogenetics (CA/SCE)  (476222) Completed 
  • Chromosome Aberation Negative 
  • Sister Chromatid Exchange Positive 
• Micronucleus  (912603) Completed 
  • Citation: Phillips, M.D., Nascimbeni, B., Tice, R.R., and Shelby, M.D. Induction of MN in Mouse BM cells: An evaluation of nucleoside analogues used in the treatment of Aids. Environ. Molec. Mutag. Vol. 18 (1991) 168-183
  • Mice: B6C3F1
  • Male Positive 
• Micronucleus  (A69895) Completed 
  • Citation: Phillips, M.D., Nascimbeni, B., Tice, R.R., and Shelby, M.D. Induction of MN in Mouse BM cells: An evaluation of nucleoside analogues used in the treatment of Aids. Environ. Molec. Mutag. Vol. 18 (1991) 168-183
  • Male Positive 
• Micronucleus  (A88072) Completed 
  • Mice: B6C3F1
  • Male Positive 
• Salmonella  (860655) Completed 
  •  Positive 

Organ Systems Toxicity

• Dominant Lethal (Female)  (DLF96001) Completed 
  • F Mice: C3H X 101
  • Mice Female Negative 
• Dominant Lethal (Male)  (DLM96001) Completed 
  • Citation: Shelby, MD, Russell, LB, Generoso, W. AZT, rodent somatic and germ cell mutagenicity and reproductive toxicity tests. Environ. Mol. Mutagen. 25 (Suppl.25): 48. (1995)
  • M Mice: C3H X 101
  • Mice Male Negative 
• 28 Days Immunotoxicity (Gavage)  (IMM20306) Report in Preparation 
  • F Mice: B6C3F1
  • Dose: 0, 134, 266, OR 400 MG/KG/DAY
• 28 Days Immunotoxicity (Gavage)  (IMM20401) Report in Preparation 
  • F Mice: B6C3F1
  • Dose: 0, 134, 266, OR 400 MG/KG/DAY -- DAMS
• 180 DAYS Immunotoxicity (Gavage)  (IMM96003) Completed 
  • F Mice: B6C3F1
  • Dose: 0, 50, 125, 250, OR 500 MG/KG/DAY
• 2 GENERATIONS Continuous Breeding (Gavage)  (RACB98003) Completed 
  • NTIS No. PB2004101163
    Citation: Azidothymidine (AZT): Multigenerational Reproductive Assessment by Continuous Breeding when Administered to Swiss CD-1® Mice by Gavage
  • M/F Mice: Swiss CD-1
  • Dose: 0, 50, 100, OR 200 MG/KG; 2X/DAY