Halina E. Caravello

Metabolism and Distribution of [2,3-14C]Acrolein in Sprague-Dawley Rats

The metabolism and disposition of [2,3‐14C]acrolein was studied in Sprague‐Dawley rats after oral or intravenous dosing. Four groups of ten rats (five male and five female) were dosed with radiolabeled acrolein intravenously at 2.5 mg kg−1 (Group 2), orally by gavage at 2.5 mg kg−1, either as a single dose (Group 3) or after 14 daily doses of unlabeled acrolein (Group 4), or orally by gavage at 15 mg kg−1 (Group 5). Urine, feces, expired air and organic volatiles were collected for 7 days, after which the animals were sacrificed and tissues collected. All samples were analyzed for total radioactivity. After 7 days, the excretory patterns of male and female rats were almost identical. Urinary excretion was highest in the intravenously dosed animals (66–69%) and lowest in the Group 5 animals (36–40%), whereas the reverse was true for feces (<2% for i.v. Group 2 animals and 28–30% for the Group 5 animals). Carbon dioxide expiration was comparable (26–31%) across all groups. Tissue concentrations of radioactivity were minimal in all groups (<1.2%), but concentrations of radioactivity were highest in the intravenous Group 2 animals. The time course of excretion for all groups was similar with the exception of the high‐dose animal group, which showed a pronounced delay in excretion during the first 12 h.

Mutagenic Activity of Acrolein in S. typhimurium and E. coli

Acrolein was tested for mutagenic activity in seven strains of Salmonella typhimurium and one strain of Escherichia coli using a preincubation assay procedure. Cytotoxicity was evident at dosing levels above 33 and 67 μg acrolein per plate in the absence and presence of S‐9 activation, respectively. Evidence of mutagenic activity was seen at non‐toxic dosing levels in S. typhimurium strains TA98 and TA100 and E. coli strain WP2 uvrA. Responses in TA98 and E. coli were marginal at best, but a firm positive mutagenic activity was noted in TA100 at 20 μg per plate without S‐9 activation and at 67 μg per plate with S‐9 activation. The results of this study demonstrate the mutagenicity of acrolein under highly controlled conditions.

Oncogenicity Study of Acrolein in Mice

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.

Developmental Toxicity of Acrolein in New Zealand White Rabbits

Pregnant New Zealand white rabbits (20 per group) were treated via stomach tube with 0.0, 0.1, 0.75, or 2.0 mg/kg/day from Days 7 through 19 of presumed gestation and subjected to cesarean sectioning on Day 29. Throughout the period of treatment, clinical observations, feed consumption, and body weights were recorded. At the termination of the study, reproductive and fetal parameters were measured. Three does died during the study, and transient effects on body weight gains and feed consumption were noted, with a subsequent rebound effect reflected in both fetal and maternal weights in the high-dose group (2 mg/kg/day). Resorptions were elevated in the high-dose group, but the effect was not statistically significant. Fetal malformations were distributed evenly among groups, and incidences were consistent with historical control data on the same strain and at the same laboratory. Higher dosage levels (range-finding study, 4.0 and 6.0 mg/kg/day) produced high incidences of maternal mortality, spontaneous abortion, resorptions, clinical signs, gastric ulceration, and/or sloughing of the gastric mucosa. Acrolein was not found to be a developmental toxicant or teratogen at doses not toxic to the does under the conditions employed in this study.

The mobility and degradation of acrolein in agricultural canals treated with magnacide® H herbicide

Abstract The decay of acrolein and its hydration product 3-hydroxypropanal (3-OH) displayed first order kinetics in agricultural canals when applied at the recommended rate for aquatic weed control. The presence of each compound following application was,transient. The dissipation half-life of acrolein was 10.2 and 7.3 hours (0.068 hr −1 and 0.028 hr −1 ) in weedy and non-weedy canals, respectively. The half-life of 3-OH, which was calculated in the weedy canal only, was 25.2 hours (0.028 hr −1 ). In the weedy canal, acrolein had dissipated 91.5% within 33.0 hours and, in the non-weedy canal, it had dissipated 48% within 7.9 hours. The results indicate that acrolein is not persistent in aquatic environments and is unlikely to pose a risk of adverse effects to nontarget receptors when used under the conditions of this study.

Reproductive Study of Acrolein on Two Generations of Rats

Four groups of 30 male and 30 female rats were intubated with 70 daily doses of acrolein at levels of 0, 1, 3, or 6 mg/kg in a dosing volume of 5 ml/kg. Rats within each dosing group (F0 generation) were then assigned to a 21-day period of cohabitation and dosing for females continued through cohabitation gestation and lactation. Males were euthanized after cohabitation. F1 generation rats were chosen from pups, and a similar pretreatment, cohabitation, gestation, and lactation regimen was accomplished resulting in F2 generation pups. Reproductive parameters, body weights, food consumption, and clinical signs were recorded and necropsies were carried out on all treated animals. Histopathologic exams were accomplished on selected reproductive tissues. In addition, gross lesions, target tissues, stomachs, and lungs were examined. For the most part, reproductive parameters were unaffected by acrolein treatment with the exception of reduced pup weights in the F1 generation pups at the high-dose level (6 mg/kg/day). Gastric lesions were noted consistently in high-dose animals and some mid-dose (3 mg/kg/day) rats. Erosions of glandular mucosa and hyperplasia/hyperkeratosis of the forestomach were the most frequent stomach lesions observed. Effects on body weight gains were noted frequently for the high-dose animals and achieved statistical significance in the mid-dose animals on several occasions. Mortality in all high-dose animals was elevated relative to control animals. Acrolein, therefore, cannot be considered a selective reproductive toxin in the rat, but does produce toxicological effects down to a dosing level of 3 mg/kg/day.