Five-hundred and sixty Sprague-Dawley rats were randomized into one control and three treatment groups (70 of each sex per group). Animals were treated by daily gavage with 0.0, 0.05, 0.5 and 2.5 mg kg-1 acrolein in water (10 ml kg-1). These dosing levels were selected as a result of a 6-week range-finding study. Ten rats of each sex per group were sacrificed at 1 year, and the remainder of the animals were treated for 102 weeks. Daily observations wer made, and various clinical, hematological and urine parameters were measured after 3, 6, 12 and 18 months of treatment and immediately prior to termination. All animals, whether found dead or sacrificed, were subject to necropsy and both absolute and relative organ weights were recorded. An extensive array of tissues were examined microscopically for all test animals. The only effects noted for treated rats that were statistically different from controls were consistent depression of creatinine phosphokinase levels, which was difficult to explain, and consistent increases in early cumulative mortalities in both males and females. There was no significantly increased incidence of microscopic lesions in treated rats, whether neoplastic or non-neoplastic. This study clearly demonstrates the lack of neoplastic response in Sprague-Dawley rats as a result of being treated with acrolein by gavage.

Forty-eight dogs were separated into four groups of six males and six females. Acrolein (0.1% aqueous) was administered in gelatin capsules to three of these groups at dosing levels of 0.1, 0.5 and 1.5 mg kg-1 day-1 based on results of a range-finding study. After 4 weeks, the high dose was increased to 2 mg kg-1 day-1. The fourth group received deionized water in the same number of gelatin capsules as the high-dose group. Dosing was 7 days per week for 53 weeks. Blood and biochemical measurements were made pretest and at 3-month intervals thereafter. At termination, all dogs were subjected to full necropsy and histological examination. The major test effect noted was frequent vomiting after dosing. This was observed to be dose-dependent and the frequency decreased with time, indicating an adaptive effect. One mid-dose female died during the test and was diagnosed as having died of severe bronchial pneumonia, probably a result of vomitus aspiration. Serum albumin, calcium and total protein values were depressed in high-dose animals throughout the study. Some variability in red blood cell parameters and coagulation times were noted but the significance of these effects was not obvious.

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.

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.

Schoener (1971) proposed that the reproductive demands of animals should be important in shaping their foraging behavior because fitness is affected. He defined two forager types: energy maximizers (reproductive success depends on energetic intake) and time minimizers (reproductive success depends on time spent in activities other than foraging), and suggested that females most often illustrate the former and males the latter. We tested whether mating activities influence the foraging behavior of Uca panacea, and the predictions that females would be energy maximizers because of their reproductive strategy and that males would also be energy maximizers because of their courtship activity. Time allocated to foraging by 800 male and female fiddler crabs (at two sites) was quantified; no significant difference in foraging time was found between the sexes. Both male and female crabs allotted a large portion of their time to foraging because both sexes depend on stored energy during their reproductive bouts. Our results show that the particular forager type can be predicted based on reproductive demands, but a forager type can not always be assigned to a particular sex without consideration of all important ecological and physiological factors determining reproductive success.

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The metabolites of [2,3-14C]acrolein in the urine and feces of Sprague-Dawley rats were identified after either intravenous administration in saline at 2.5 mg/kg or oral administration by gavage as an aqueous solution as either single or multiple doses at 2.5 mg/kg or as a single dose of 15 mg/kg. Selected urine and feces samples were pooled by sex and collection interval and profiled by combinations of reverse-phase, anion-exchange, cation-exchange, and ion-exclusion high-performance liquid chromatography (HPLC). Feces were also profiled by size-exclusion chromatography. Metabolites were identified by comparison with well-characterized standards by HPLC and by mass spectrometry. The urinary metabolites were identified as oxalic acid, malonic acid, N-acetyl-S-2-carboxy-2-hydroxyethylcysteine, N-acetyl-S-3-hydroxypropylcysteine, N-acetyl-S-2-carboxyethylcysteine, and 3-hydroxypropionic acid. The fecal radioactivity from the oral dose groups was partitioned into methanol-soluble, water-soluble, and insoluble radioactivity, some of which could be liberated by dilute acid hydrolysis. HPLC analysis of these extracts revealed no discrete metabolites. Size-exclusion chromatography indicated a molecular weight range of 2,000 to 20,000 Da for the radioactivity, which was unaffected by hydrolysis at reflux with 6 M acid or base. This radio-activity was thought to be a homopolymer of acrolein, which was apparently formed in the gastrointestinal tract. The pathways of acrolein metabolism were epoxidation followed by conjugation with glutathione, Michael addition of water followed by oxidative degradation, and glutathione addition to the double bond either following or preceding oxidation or reduction of the aldehyde. The glutathione adducts were further metabolized to the mercapturic acids.

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