Teratogenicity acrolein

After intraamniotic injection, acrolein is teratogenic to rats in vivo but not in vitro. When administered intraamniotically to the whole embryo culture system of the rat on day 13 of gestation, acrolein caused edema, hydrocephaly, open eyes, cleft palate, abnormal umbilical cord, and defects of the limbs and face (Slott and Hales 1986). Beauchamp etal. (1985) suggest that acrolein-associated teratogenicity is caused by acrylic acid, an acrolein metabolite. Acrylic acid injected into amniotic fluid of rats on day 13 of gestation produced a dose-dependent increase in the percent of fetuses with skeletal and other abnormalities (Beauchamp et al. 1985). 

Intraamniotic injection route. Embryos given 0.1, 1, 10, or 100 pg of acrolein on day 13 of gestation examined on day 20 of gestation Intraperitoneal injection route 98-100% dead at 10 and 100 pg 85% of live fetuses receiving 1 pg were malformed (edema, hydrocephaly, cleft palate, defects of limbs and tail) no teratogenic effects at 0.1 pg 6... 

Slott VL, Hales BF Teratogenicity and embryolethality of acrolein and structurally related compounds in rats. Teratology 32 65-72, 1985... 

Slott, V.L. Hales, B.F. (1985) Teratogenicity and embryolethality of acrolein and structurally... 

Flales BF. 1982. Comparison of the mutagenicity and teratogenicity of cyclophosphamide and its active metabolites, 4-hydroxycyclophosphamide, phosphoramide mustard, and acrolein. Cancer Res 42 3016-3021. 

Hoberman AM. 1987. Developmental toxicity (embryo/fetal toxicity and teratogenic potential) study of acrolein administered orally (stomach tube) to New Zealand white rabbits. Performed by Argus Research Laboratories, Inc., Horsham, PA, for Baker Performance Chemicals, Inc., Houston, TX. [Peer Reviewed],... 

Mirkes PE, Fantel AG, Greenaway JC, et al. 1981. Teratogenicity of cyclophosphamide metabolites phosphoramide mustard, acrolein, and 4-ketochlorophosphamide in rat embryos cultured in vitro Toxicol Appl Pharmacol 58 322-330. 

Mirkes PE, Greenaway JC, Rogers JG, et al. 1984. Role of acrolein in cyclophosphamide teratogenicity in rat embryos in vittCL Toxicol Appl Pharmacol 72 281-291. 

Schmid BP, Goulding E, Kitchin K, et al. 1981. Assessment of the teratogenic potential of acrolein and cyclophosphamide in a rat embryo culture system. Toxicology 22 235-244. 

Slott V, Hales BF. 1985. Effect of glutathione (GSH) depletion by buthionine sulfoximine (BSO) on the in vitro teratogenicity and embryolethality of acrolein (AC). Teratology 31 33A. 

Slott VL, Hales BF. 1986. The embryolethality and teratogenicity of acrolein in cultured rat embryos. Teratology 34 155-163. 

Stahlmann R, Bluth U, Neubert 1984. Teratogenic potential of the cyclophosphamide metabolite acrolein. Teratology 29 33A. 

Cyclophosphamide requires metabolic activation to form the teratogenic metabolites, phosphoramide mustard, and acrolein (Figure 34.5). The former metabolite produces single-stranded DNA breaks, DNA-DNA and DNA-protein crosslinking. In contrast, acrolein preferentially binds to proteins, and it concentrates in the... 

Acrolein was mutagenic to certain microorganisms and to the fruit fly mutagenicity may be due, in part, to glycidaldehyde, an acrolein metabolite. Injected into the amniotic fluid, acrolein is teratogenic to rats teratogenicity may be due to acrylic acid, another acrolein metabolite. There is limited evidence that acrolein acts as a weak carcinogen and tumor promoter. Acrolein interacts with other... 

---