Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.
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PMID:Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. 1095 42

2-Butoxyethanol is a member of a family of ethylene glycol monoalkyl ethers. It is used extensively as a solvent in surface coatings such as lacquers, enamels, varnishes, and latex paint; in paint thinners, paint stripping formulations, and inks; and in degreasers and industrial and household cleaners. 2-Butoxyethanol was nominated for study because of its widespread use in industrial and consumer applications, the potential for exposure to workers and the general population, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to 2-butoxyethanol (greater than 99% pure) by inhalation (primary route of human exposure) for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and the bone marrow of male F344/N rats and B6C3F1 mice. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. One female rat in the 250 ppm group was killed moribund during week 8; four females in the 500 ppm group were killed moribund during week 1 and one during week 5. Final mean body weights of females exposed to 500 ppm were significantly less than those of the chamber controls. Clinical findings included abnormal breathing, pallor, red urine stains, nasal and eye discharge, lethargy, and increased salivation and/or lacrimation. Due to vascular thrombosis and infarction in the tail vertebrae of 500 ppm female rats, the tails became necrotic and either sloughed off or were chewed off. The primary effect on the hematopoietic system was an anemia characterized as macrocytic, normochromic, and regenerative in males exposed to 125 ppm or greater and, to a greater extent, in all exposed groups of females. Compared to the chamber controls, kidney weights of males exposed to 500 ppm and females exposed to 125 ppm or greater and liver weights of males exposed to 250 or 500 ppm and females exposed to 125 ppm or greater were significantly increased, and thymus weights of females exposed to 500 ppm were significantly less. In female rats killed moribund, there was considerable histologic evidence of thrombosis in tissues and organs including the nasal cavity, incisors, liver, lung, and heart. In addition to thrombosis, infarction occurred in the vertebrae of the tail resulting in necrosis and loss of the distal portion of the tail. There were also inflammation, necrosis, and ulceration of the forestomach; necrosis and centrilobular degeneration of the liver; renal tubule degeneration; and atrophy of the spleen and thymus. Exposure-related increases in the incidences of Kupffer cell pigmentation, forestomach inflammation and epithelial hyperplasia, bone marrow hyperplasia, splenic hematopoietic cell proliferation, and renal tubule pigmentation were observed in male and/or female rats surviving to the end of the study. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. Two male and two female mice exposed to 500 ppm died and two males and two females were killed moribund during the first 2 weeks of the study. Final mean body weights of 125, 250, and 500 ppm male mice were significantly less than those of the chamber controls. Clinical findings were observed only in 500 ppm males and females that died or were killed moribund and included abnormal breathing, red urine stains, and lethargy. Hematologic evaluation indicated an anemia that was characterized as normocytic, normochromic, and regenerative in mice exposed to 62.5 ppm or greater; the anemia was more pronounced in females. Liver weights of males exposed to 500 ppm were significantly greater than the chamber controls. In mice either dying early or killed moribund, there were inflammation, necrosis, and ulceration of the forestomach; mediastinal pleura and peritoneal inflammationmmation associated with the forestomach lesions; liver necrosis; renal tubule degeneration; atrophy of the spleen, thymus, and mandibular and mesenteric lymph nodes; and degeneration of the testis. Exposure-related increases in the incidences of hematopoietic cell proliferation and hemosiderin pigmentation of the spleen, Kupffer cell hemosiderin pigmentation of the liver, inflammation and epithelial hyperplasia of the forestomach, and renal tubule hemosiderin pigmentation occurred in male and/or female mice surviving to the end of the study. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31.2, 62.5, or 125 ppm, 6 hours per day, 5 days per week for 104 weeks. For hematology and bone marrow analyses, additional groups of 27 male and 27 female rats were exposed to 0, 62.5, or 125 ppm for evaluation at 3, 6, and 12 months and nine male and nine female rats were exposed to 31.2 ppm for evaluation at 3 (hematology only) and 6 months. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber control groups. The mean body weights of females exposed to 125 ppm were generally less than the chamber control group. Hematology and Bone Marrow Cellularity: The most consistent exposure-related effect on the hematopoietic system was an exposure concentration-related mild macrocytic, normochromic, regenerative anemia present at 3, 6, and 12 months, with females more affected than males. Significant increases in bone marrow cellularity and decreases in the myeloid/erythroid ratio relative to the chamber controls were observed at all time points in females exposed to 125 ppm, and a decrease in the myeloid/erythroid ratio was observed in males exposed to 125 ppm at 12 months. Pathology Findings: The incidence of benign or malignant pheochromocytoma (combined) of the adrenal medulla in females exposed to 125 ppm was not significantly increased compared to the chamber controls but exceeded the historical control range. Exposure-related increases in the incidences of hyaline degeneration of the olfactory epithelium and Kupffer cell pigmentation of the liver were observed in male and female rats. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 62.5, 125, or 250 ppm, 6 hours per day, 5 days per week for 104 weeks. For hematology and bone marrow analyses, additional groups of 30 male and 30 female mice were exposed to 0, 62.5, 125, or 250 ppm for evaluation at 3, 6, and 12 months. Survival and Body Weights: Survival of male mice exposed to 125 or 250 ppm was significantly less than that of the chamber control group. The mean body weights of exposed males were generally less than those of the chamber control group during the last 6 months of the study. The mean body weights of exposed female mice were less than those of the chamber control group; the reductions were greater and occurred earlier than those observed in males. Hematology: The most consistent exposure-related effect on the hematopoietic system was an exposure concentration-related minimal normocytic, normochromic, regenerative anemia present at 3, 6, and 12 months, with females affected slightly more than males. Pathology Findings: In females exposed to 250 ppm, incidences of forestomach squamous cell papilloma and squamous cell papilloma or carcinoma (combined) were significantly increased relative to the chamber controls, and these incidences exceeded the ranges in historical chamber controls. In 2-butoxyethanol exposed males, there were possible exposure-related increases in the incidences of squamous cell papilloma of the forestomach, although the increases were not significant and the incidences were within the historical control range for chamber controls. Accompanying these neoplasms in females and, to a lesser extent, in males were exposure-related increases in the incidences of ulcer and epithelial hyperplasia of the forestomach. In male mice exposed to 250 ppm, the incidence of hemangiosarcoma of the liver was significantly increased relative to chamber controls and exceeded the range in historical controls; in addition, there were possible exposure-related increases in the incidence of hepatocellular carcinoma. Incidences of hemosiderin pigmentation in the Kupffer cells were significantly increased in 125 and 250 ppm males and all exposed groups of females. The incidences of splenic hematopoietic cell proliferation and hemosiderin pigmentation were generally increased in males and females, and the incidences of bone marrow hyperplasia were increased in males. The incidences of hyaline degeneration of the olfactory and respiratory epithelia of the nose were increased in female mice. GENETIC TOXICOLOGY: 2-Butoxyethanol did not induce mutations in any of the S. typhimurium strains tested, with or without induced hamster or rat liver S9. 2-Butoxyethanol induced cycle delay but did not induce either sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells with or without S9. 2-Butoxyethanol did not induce micronuclei in bone marrow cells of male rats or mice administered the chemical by intraperitoneal injection three times at 24-hour intervals. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of 2-butoxyethanol in male F344/N rats exposed to 31.2, 62.5, or 125 ppm. There was equivocal evidence of carcinogenic activity of 2-butoxyethanol in female F344/N rats based on the increased combined incidences of benign or malignant pheochromocytoma (mainly benign) of the adrenal medulla. There was some evidence of carcinogenic activity of 2-butoxyethanol in male B6C3F1 mice based on increased incidences of hemangiosarcoma of the liver. A marginal increase in the incidences of forestomach squamous cell papilloma and an increase in the incidences of hepatocellular carcinoma may have been exposure related. There was some evidence of carcinogenic activity of 2-butoxyethanol in female B6C3F1 mice based on increased incidences of fore stomach squamous cell papilloma or carcinoma (mainly papilloma). Increased incidences of forestomach neoplasms in male and female mice occurred in groups in which ulceration and hyperplasia were also present. Exposure to 2-butoxyethanol caused a mild regenerative anemia and effects secondary to the anemia. Synonyms: 2-Butoxy-1-ethanol; m-butyl ether; butyl glycol; ethylene glycol monobutyl ether Trade name: Butyl Cellosolve
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PMID:NTP Toxicology and Carcinogenesis Studies 2-Butoxyethanol (CAS NO. 111-76-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1257 79

OBJECTIVE: To describe an unusual case with clinical features of the antiphospholipid syndrome. DESCRIPTION: White child, two years and six months old, with renal failure, renal arterial thrombosis, and diagnosis of antiphospholipid syndrome was hospitalized with a history of abdominal pain, pallor, lethargy, and anuria for 36 hours. On physical examination, the patient showed malnutrition, high blood pressure, moderate edema, and hypochondrial pain. Laboratory findings included: urea=112mg/dl, serum creatinine= 4.5 mg/dl, blood pH= 7.47, blood bicarbonate= 12.8 mmol/L, K=7.2 mEq/L. Peritoneal dialysis was started and maintained for 11 days. After 7 weeks, the patient still needed anti-hypertensive drugs and the renal function was still abnormal. Renal biopsy was performed and revealed renal infarction. The result of Doppler ultrasonography revealed absent renal blood flow on the right side. Renal arteriography showed total occlusion of the right renal artery. Results for collagen diseases were negative. A right nephrectomy was performed and the blood pressure was controlled. The child was hospitalized again at 5 years and 8 months old with episodes of absence seizures and abdominal and precordial pain. Anticardiolipin antibody test was positive. The child is now 7 years old, asymptomatic, with negative anticardiolipin antibody, and has been under regular follow-up. COMMENTS: Children with arterial thrombosis should be investigated for a possible association with the antiphospholipid antibody syndrome even in the absence of collagen disease.
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PMID:[Renal arterial thrombosis and the antiphospholipid antibody syndrome: a case report] 1464 33

A 10-year-old, crossbreed dog was presented with a history of severe lethargy, pyrexia and inappetence of several days' duration. Clinical examination revealed pallor of the mucous membranes, petechiae, generalised lymphadenopathy and effusions in multiple joints. Laboratory evaluation showed severe anaemia and thrombocytopenia, with positive in-saline agglutination and the presence of antiplatelet antibodies. The DNA of Anaplasma phagocytophilum, an endemic granulocytic rickettsial parasite, was detected by PCR. A poor response to doxycycline and immunosuppressive therapy with corticosteroids was seen. Euthanasia was performed after the development of disseminated intravascular coagulation. Postmortem examination demonstrated changes consistent with the development of disseminated intravascular coagulation and infection with granulocytic ehrlichiosis. This case documents the presence of canine granulocytic ehrlichiosis caused by A phagocytophilum in the U.K., and highlights the range of clinical signs and clinicopathological abnormalities that may be observed in infected dogs.
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PMID:Immune-mediated haemolytic anaemia and thrombocytopenia associated with Anaplasma phagocytophilum in a dog. 1630 Jan 16

Ten out of 47 calves that were born in a small Brahman herd from southern Brazil developed progressive muscular weakness and tremors, lethargy and poor body condition. Necropsy was performed on three affected animals. The only gross lesion detected was paleness of the muscles of the trunk and limbs. Multiple cytoplasm vacuoles located in different tissues were the principal microscopic lesions. Vacuoles were particularly evident in skeletal muscles and myocardium. PAS-positive granules were numerous in skeletal muscle fibres and Purkinje fibres of the myocardium, but were also observed in the neurons of the brain and spinal cord, and in the vascular smooth muscle fibres from all the examined tissues. Pretreatment with diastase completely abolished the PAS reactivity. The vacuoles reacted strongly to Griffonia simplicifolia II and Concanavalia ensiformes lectins, whose biding pattern has been reported as useful for demonstration of glycogen. Examination of the electron micrographs revealed that glycogen was free within the cytoplasm or accumulated in membrane-bound granules of several tissues, especially in striated muscle, liver and neurons of the CNS. These findings were consistent with generalized glycogenosis.
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PMID:Lectin-histochemistry: glycogenosis in cattle. 1650 5

A case of Red-bellied Black snake envenomation resulting in intravascular haemolytic anaemia, rhabdomyolysis and anuric renal failure is described in the dog. A 12-year-old female desexed Golden Retriever was presented with a 15 hour history of profuse salivation, progressive lethargy, obtundence, inappetence and collapse. Significant findings on clinical examination were pallor, icterus, tachypnoea and dyspnoea with increased respiratory sounds and crackles in all lung fields. Generalised abdominal and muscular pain was apparent and dark red-brown urine was present around the perineal region. A diagnosis of Red-bellied Black snake (Pseudechis porphyriacus) envenomation was made and the dog was treated with intravenous fluid therapy, Tiger/Brown snake antivenom, packed red cell transfusions and Intermittent Positive Pressure Ventilation. Continued clinical deterioration occurred and a diagnosis of acute renal failure secondary to myohaemoglobinuric pigmenturia was made 12 hours after admission. Intensive treatment was attempted with diuresis and volume expansion. Oliguria and subsequent anuria ensued and the dog was euthanased due to a grave prognosis and lack of clinical response to treatment. Necropsy examination revealed muscular necrosis, accumulation of fluid in the thoracic and peritoneal cavities, and marked renal tubular necrosis with intraluminal occlusion secondary to pigmentary casts.
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PMID:Anuric renal failure in a dog after red-bellied black snake (Pseudechis porphyriacus) envenomation. 1673 24

In this study which was carried over a period of 2 years, from 2003 to 2004, 270 paediatric patients with active Tuberculosis (TB) disease attending the OPD of S.N. Medical College, Agra were screened for Human Immunodeficiency Virus (HIV)-1/2 antibodies. Of these, 23 were found to be HIV-positive. Seroprevalence of HIV infection among paediatric TB patients in Agra is 8.51% (23/270). The HIV infection was found to be significantly higher, i.e. 82.61% in male children than in female children, i.e. 17.39%. Among the age groups, which were divided into < or =1, 2-5, 6-10 and 11-15 years, maximum cases of HIV-positivity, i.e. 65.22% was observed in the age group, 2-5 years of age. Among the HIV-positive children with TB, 86.75% were of pulmonary and 13.04% were of extra-pulmonary type. Among the vaccinated children, 65.22% were found to be HIV-positive, while 34.78% of the HIV-positive children were not BCG vaccinated. HIV-positive children are more likely to suffer from prolonged fever, weight loss, failure to thrive, developmental delay, stunted growth, cough, anorexia, lethargy, lower respiratory tract infections (LRTI) and hepatosplenomegaly while HIV negative are more likely to suffer from fever, diarrhoea, lymphadenitis, pallor and LRTI. 82.60% (19/23) of these TB patients had a history of positive contact with HIV, i.e. one of the parents was HIV-infected. The mode of transmission of HIV infection among paediatric TB patients was perinatal as revealed during the counselling sessions (pre-test and post-test) of both the parents.
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PMID:Seroprevalence of HIV infection among paediatric tuberculosis patients in Agra, India: a hospital-based study. 1690 56

Clinical observations of Babesia canis infection in 63 dogs during a 1-year period are summarised, demonstrating the pathogenicity of the Babesia strain endemic in Hungary. Most patients had babesiosis in the spring and autumn, correlating with the seasonal activity of ticks. Male animals appeared in higher numbers, probably due to an overrepresentation of outdoor dogs. Uncomplicated babesiosis was diagnosed in 32 cases. The disease affected dogs of any age in this study. Symptoms were similar to those published from other parts of the world: lethargy, fever, splenomegaly, pallor, icterus, haemoglobinuria and presence of ticks were the most common observations. Thrombocytopenia, lymphopenia and neutropenia were frequent haemogram changes. Imidocarb appeared to be highly effective in eliminating the Babesia infection. Thirty-one animals demonstrated babesiosis with complications. Most Rottweilers (7/9) developed complicated disease. Old age was a risk factor for multiple complications. Multiple organ manifestations had poor prognosis. Hepatopathy (44%), pancreatitis (33%), acute renal failure (ARF; 31%) and disseminated intravascular coagulation (DIC; 24%) were frequent complications, while immune-mediated haemolytic anaemia (IMHA; 10%), acute respiratory distress syndrome (ARDS; 6%) and cerebral babesiosis (3%) were rarely observed. There was a significant difference between the mean age of dogs having uncomplicated disease, babesiosis with a single complication and babesiosis with multiple complications (3.4, 4.8 and 8.6 years, respectively, p < 0.001). The recovery rate (78, 68 and 25%, respectively, p = 0.005) and mortality rate (3, 21 and 67%, respectively, p < 0.001) also tended to differ significantly in these groups. Systemic inflammatory response syndrome (SIRS) and DIC are two possible pathways leading to multiple organ dysfunction syndrome (MODS) in babesiosis. DIC was found to predict MODS more sensitively in this study than SIRS: there were 6 animals developing MODS out of 11 identified with DIC, while only 5 dogs developed MODS out of 22 having SIRS.
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PMID:Clinical manifestations of canine babesiosis in Hungary (63 cases). 1702 Jan 40

The present study identifies an emerging disease associated with an aquatic Francisella-like bacterium that can cause mortality in hybrid striped bass Morone chrysops x M. saxatilis reared intensively in freshwater. Clinically affected fish were lethargic, had scattered haemorrhagic cutaneous lesions and diffuse gill pallor. The head kidney and spleen were markedly swollen and contained numerous interstitial granulomas; histological examination revealed small, pleomorphic Gram-negative coccobacilli within vacuolated cells. The bacterium could not be cultured from head kidney homogenates either with standard or enriched microbiological media or following inoculation of a Chinook salmon embryo (CHSE)-214 cell line. No amplification product was obtained from head kidney DNA by polymerase chain reaction (PCR) assay using Piscirickettsia salmonis-specific primers. PCR analysis of infected head kidney homogenate with primers designed for the eubacterial 16S rRNA produced a single amplicon. Phylogenetic analysis of this DNA sequence demonstrated that the sequence aligned most closely with members of the genus Francisella, identified from tilapia Oreochromis spp. in Taiwan and an aquatic Francisella species that was recently isolated from the three-line grunt Parapristipoma trilineatum in Japan. This Francisella-like disease was transmitted to naive hybrid striped bass fingerlings by intraperitoneal injection of tissue homogenates prepared from a natural outbreak. All fish developed gross and histological lesions identical to those from natural outbreaks. Intracellular Gram-negative bacteria were observed within the cytoplasm of cells (presumably macrophages) within the granulomas, but bacteria were not recovered. The 16S DNA sequence of the bacterium obtained from tissues of experimentally infected fish was identical to that obtained from the fish used as infected donor tissue.
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PMID:Aquatic Francisella-like bacterium associated with mortality of intensively cultured hybrid striped bass Morone chrysops x M. saxatilis. 1714 Jan 36

Allyl acetate, allyl alcohol, and acrolein are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents and food additives. Male and female F344/N rats and B6C3F(1) mice received allyl acetate, allyl alcohol, or acrolein by gavage for 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, cultured Chinese hamster ovary cells, rat bone marrow erythrocytes, and mouse peripheral blood erythrocytes. Groups of 10 male and 10 female rats were administered 0, 6, 12, 25, 50, or 100 mg allyl acetate/kg body weight, 0, 1.5, 3, 6, 12, or 25 mg/kg allyl alcohol, or 0, 0.75, 1.25, 2.5, 5, or 10 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. Groups of 10 male and 10 female mice were administered 0, 8, 16, 32, 62.5, or 125 mg/kg allyl acetate, 0, 3, 6, 12, 25, or 50 mg/kg allyl alcohol, or 0, 1.25, 2.5, 5, 10, or 20 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. In the allyl acetate rat study, all males and females in the 100 mg/kg groups died or were killed moribund by day 8; there were no other deaths. In the allyl alcohol study, all rats survived to the end of the study except one 6 mg/kg female. In the acrolein rat study, eight males and eight females in the 10 mg/kg groups died by week 9 of the study. Two males in the 2.5 and 5 mg/kg groups and one or two females in the 1.25, 2.5, and 5 mg/kg groups also died early; two of these deaths were gavage accidents. In the allyl acetate mouse study, all males and females in the 125 mg/kg group died during the first week of the study. All other early deaths, except five 62.5 mg/kg males and one 32 mg/kg female, were gavage accidents. In the allyl alcohol mouse study, one 50 mg/kg female died due to a gavage accident; all other animals survived to the end of the study. In the acrolein mouse study, all males and females administered 20 mg/kg died during the first week of the study. All other early deaths, except one male and one female administered 10 mg/kg, were unrelated to chemical administration. The concentration of 3-hydroxypropyl mercapturic acid (3-HPM) in the urine of rats and mice was determined after the first dose of chemical and at the end of the 14-week study. At both time points, the concentrations of 3-HPM in the urine of animals that received allyl acetate or allyl alcohol increased linearly with dose. In animals dosed with acrolein, the concentrations of 3-HPM exhibited a nonlinear increase with dose at the first time point. At the end of the study, the concentration of 3-HPM in the urine of animals dosed with acrolein was linear with dose except at the highest concentration administered. Since urine volumes were not recorded during the urine collection, complete quantitation of these data was not possible. The final mean body weights and mean body weight gains of male rats administered 12 or 50 mg/kg allyl acetate and of male and female rats administered 10 mg/kg acrolein were significantly less than those of the vehicle controls. The mean body weight gain of male mice in the 50 mg/kg group in the allyl alcohol study was also less than that of the vehicle controls. Final mean body weights and mean body weight gains of dosed female rats and male and female mice in the allyl acetate studies, male and female rats and female mice in the allyl alcohol studies, and male and female mice in the acrolein studies were generally similar to those of the respective vehicle controls. Clinical findings related to allyl acetate administration included pallor, eye or nasal discharge, ruffled fur, lethargy, diarrhea, and thinness among rats in the 100 mg/kg groups and lethargy, abnormal breathing, thinness, and ruffled fur among mice that died early. In the acrolein study, clinical findings included abnormal breathing, eye or nasal discharge, ruffled fur, thinness, and lethargy in rats in the 10 mg/kg groups. The liver weights of male rats administered 25 mg/kg allyl alcohol, female rats administered 50 mg/kg allyl acetate or 5 or 10 mg/kg acrolein, and male mice administered 10 mg/kg acrolein were significantly greater than those of the vehicle controls. Female rats administered 10 mg/kg acrolein had significantly lower absolute and relative thymus weights than did the vehicle controls. Female rats administered 25 mg/kg allyl alcohol spent more time in diestrus and less time in metestrus than the vehicle controls. The estrous cycles of female mice dosed with 16 or 32 mg/kg allyl acetate were significantly longer than that of the vehicle controls. Gross lesions related to allyl acetate treatment were observed in the liver, forestomach, and thorax/abdomen of male and female rats in the 100 mg/kg groups. Microscopically, the incidences of forestomach squamous epithelial hyperplasia were significantly increased in male rats administered 12 mg/kg or greater, female rats administered 25 or 50 mg/kg, male mice administered 32 or 62.5 mg/kg, and female mice administered 16, 32, or 62.5 mg/kg. Forestomach necrosis, hemorrhage, and inflammation were present in most rats in the 100 mg/kg groups, and the incidence of hemorrhage in 125 mg/kg male mice was increased; male mice in the 62.5 and 125 mg/kg groups and 125 mg/kg female mice had significantly increased incidences of glandular stomach hemorrhage. Increased incidences of several liver lesions occurred in male or female rats administered 50 or 100 mg/kg, and to a lesser extent in 25 mg/kg rats, 62.5 mg/kg male mice, and 125 mg/kg male and female mice. Bone marrow hyperplasia, hemorrhage or depletion in the mediastinal, mandibular, and mesenteric lymph nodes, hemorrhage and necrosis of the thymus, and hematopoietic cell proliferation of the red pulp were also observed in 100 mg/kg rats. Increased incidences of necrosis in the mandibular and mesenteric lymph nodes, spleen, and thymus were observed in 62.5 and 125 mg/kg mice. Male and female rats administered 6 mg/kg allyl alcohol or greater and male and female mice administered 12 mg/kg allyl alcohol or greater had significantly increased incidences of squamous hyperplasia of the forestomach epithelium. Female rats in the 25 mg/kg group had significantly increased incidences of bile duct hyperplasia and periportal hepatocyte hypertrophy in the liver. Incidences of portal cytoplasmic vacuolization were significantly increased in 50 mg/kg male mice and female mice in the 25 and 50 mg/kg groups. Gross lesions related to acrolein treatment were observed in the forestomach and glandular stomach of male and female rats in the 10 mg/kg groups and 20 mg/kg female mice. Microscopically, the incidences of squamous hyperplasia of the forestomach epithelium were significantly increased in male rats in the 5 and 10 mg/kg groups, female rats administered 2.5 mg/kg or greater, and male and female mice administered 2.5, 5, or 10 mg/kg. Male and female rats in the 10 mg/kg groups and 20 mg/kg male and female mice had significantly increased incidences of glandular stomach hemorrhage. Female mice in the 20 mg/kg group also had significantly increased incidences of glandular stomach inflammation and epithelial necrosis. Allyl acetate was mutagenic in S. typhimurium strains TA100 and TA1535, in the absence of S9 activation. With S9, no mutagenicity was detected in these two strains; negative results were obtained in strains TA97 and TA98, with and without S9. Allyl alcohol was not mutagenic in four strains of S. typhimurium, with or without S9 metabolic activation. Acrolein, tested in a preincubation protocol, was weakly mutagenic in S. typhimurium strain TA100 in the presence of 10% induced rat liver S9. Equivocal results were obtained in strains TA100 and TA1535 with 10% induced hamster liver S9. Negative results were obtained with TA97, TA98, and TA1538 under all test conditions, and acrolein gave negative results in all four S. typhimurium strains tested for mutation induction under a vapor protocol. No induction of micronuclei was noted in bone marrow erythrocytes of male rats administered allyl acetate by gavage three times at 24-hour intervals. No significant increases in micronucleated erythrocytes were noted in bone marrow samples from male rats administered allyl alcohol by intraperitoneal injection for 3 days. A small, but significant increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of female mice administered allyl acetate by gavage for 14 weeks; no increase was observed in male mice. No increases in the frequencies of micronucleated normochromatic erythrocytes were observed in the peripheral blood of male or female mice administered allyl alcohol or acrolein by gavage for 14 weeks. Acrolein induced sister chromatid exchanges in cultured Chinese hamster ovary cells in the absence, but not the presence, of S9; it did not induce chromosomal aberrations, with or without S9. Results of three independent Drosophila melanogaster sex linked recessive lethal tests in which acrolein was administered to adult flies via feeding or injection and to larvae via feeding were negative.
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PMID:NTP Technical Report on the comparative toxicity studies of allyl acetate (CAS No. 591-87-7), allyl alcohol (CAS No. 107-18-6) and acrolein (CAS No. 107-02-8) administered by gavage to F344/N rats and B6C3F1 mice. 1716 Jan 5


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