Oncogenicity Study of Acrolein in Mice

Abstract

Five hundred seventy CD-1 mice were divided equally by gender and assigned to three groups of 70 per gender and one group of 75 per gender. The first three groups were dosed via oral intubation at 0, 0.5, and 2.0 mg/kg/day while the larger groups were dosed at 4.5 mg/kg/day. Observations were made twice daily and blood smears taken at 12 and 18 months. All animals were sacrificed at 18 months; organs were weighed and examined grossly and microscopically. Treated animals showed decreased body weight gain and male mice demonstrated increased mortality, particularly at the high-dose level. Gross and microscopic lesions were not obviously dose dependent. In this study, acrolein was not shown to have oncogenic properties.

An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes

“…Based on these results it is concluded that DNA adduct formation caused by the 18 food-borne acyclic α,β-unsaturated aldehydes may be negligible. This conclusion is in line with what was previously concluded for trans-2-hexenal (Kiwamoto et al, 2012;Kiwamoto et al, 2013) and may be corroborated by findings of chronic studies with rats or mice orally exposed to 2-propenal (Parent et al, 1991;Parent et al, 1992;NTP, 2006) that did not reveal increased tumour development up to exposures of 10 mg 2-propenal/kg bw, whereas higher dose levels induced mortality within a week (NTP, 2006). The PBK/D model predicted a formation of 27 adduct/10 8 nt in the liver at an exposure of 10 mg 2-propenal/kg bw, which is still within Table 5, or at 0.017 mg/kg bw when the exposure level of a compound is unknown.…”

Toxicology and risk assessment of acrolein in food

“…Animals were exposed daily to 0.5, 2.0 and 4.5 mg acrolein/kg bw (dissolved in water) over 18 months by gavage. The treated animals showed a reduced bw increase and a higher mortality in the higher dose group [66].…”

“…In chronic studies in which acrolein was administered dissolved in water to rats and mice, in doses of up to 2.5 mg/kg bw/day (concentration in water: 0.25 mg/mL) for rats and 4.5 mg/kg bw/day (concentration 0.45 mg/mL) for mice, increased mortality was reported as a primary endpoint. The underlying cause was not discussed or was designated as unclear [39,66]. In a reproduction toxicity study with rats, an erosion of the glandular stomach as well as hyperplasias/hyperkeratosis of the forestomach were reported at a mean dosage of 3.0 mg/kg bw/day (concentration in water 0.6 mg/mL) [41].…”

Toxicology of Volatile Organic Compounds in Indoor Air and Strategy for Further Research

“…As a consequence it cannot be excluded that acetal dehyde at non-cytotoxic concentrations is capable of inducing nasal cancer in rats. [54,55], In addition, the pathology of an earlier published 100-week oral study suggesting an increased incidence of adrenocortical ade nomas in acrolein-treated Fisher 344 rats [56] was re-evaluated and found to be negative [54], On the basis of these Findings it seems reasonable to conclude that, despite the conflicting data on genotoxicity, acrolein in foods and drinks is no cancer risk factor. However, since acrolein has been shown to induce DNA single strand breaks and DNA-protein cross-links in human bronchial epithelium [40,41], and the aforementioned 78-week inhalation study in hamsters does not meet modern standards for long-term carcinogenicity studies in rodents, it is deemed desirable to perform a long-term inhalation study with acrolein in rats, designed according to internationally adopted guidelines and conducted under the regulations of Good Laboratory Practice.…”

“…No clinical and pathological effects were noted at 125 ppm. Upon oral administration in rats, the 'no-observed- 'high-dose-phenomenon' [13], This may also be true for acetaldehyde but further investigations including long-term inhalation studies using non-cytotoxic exposure levels, and studies into the mechanism of acetaldehyde carcinogenesis are needed to substantiate this assumption and to allow quantitative risk assessment [68], Since acrolein is a major VOC in indoor air, a long term inhalation carcinogenicity study in rats should be carried out, despite the fully negative results obtained in the recently completed 2-year oral studies in rats and mice [54,55], If acrolein would also be negative in such inhala tion studies, it seems highly desirable to find an explana tion for the non-carcinogenicity of this highly reactive, potent DNA-protein cross-linking aldehyde.…”