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Influence of strain and sex on the metabolic profile of rats in repeated dose toxicological studies. 2009

V Strauss, and J Wiemer, and E Leibold, and H Kamp, and T Walk, and W Mellert, and R Looser, and A Prokoudine, and E Fabian, and G Krennrich, and M Herold, and B van Ravenzwaay
BASF SE Experimental Toxicology and Ecology, Z 470, 67056 Ludwigshafen, Germany.

The impact of the strain on the metabolite profile of plasma samples in rats dosed with 2500 ppm 2-methyl-4-chlorophenoxyacetic acid (MCPA acid) or 45 mg/kg bw/day 4-chloro-3-nitroaniline (4C3N) for 4 weeks was evaluated. Four different strains were used: two Wistar strains (Crl:WI(Han), Han:RCC:WIST(SPF)), one Sprague-Dawley (Crl:CD) and one Fisher strain (F-344/Crl). The metabolite profiles in the plasma were measured by LC-MS and GC-MS. The profound changes of the metabolite values induced by the MCPA acid treatment outweighed slight deviations caused by physiological variations between the different rat strains. The metabolome changes of the MCPA acid in all strains could be related to toxicological "mode of action" patterns (peroxisome proliferator, renal organic anionic transporter inhibition) with Crl:WI(Han) rats as reference strain. 4C3N administration led to extravascular hemolytic anemia with a small number of metabolome changes, which were strain dependent. The metabolome pattern associated with "hemolytic anemia" established with the reference strain (Crl:Wi(Han)) was not sufficiently similar in other strains. Thus, comparable metabolome profiles were obtained in different rat strains for a compound inducing profound metabolite changes. For a compound with a weak profile the results were more variable and appeared to be strain dependent.

UI MeSH Term Description Entries
D008297 Male Males
D008456 2-Methyl-4-chlorophenoxyacetic Acid A powerful herbicide used as a selective weed killer. MCPA,Agroxone,Methoxone,2 Methyl 4 chlorophenoxyacetic Acid
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001772 Blood Cell Count The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES. Blood Cell Number,Blood Count, Complete,Blood Cell Counts,Blood Cell Numbers,Blood Counts, Complete,Complete Blood Count,Complete Blood Counts,Count, Blood Cell,Count, Complete Blood,Counts, Blood Cell,Counts, Complete Blood,Number, Blood Cell,Numbers, Blood Cell
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D005260 Female Females
D006540 Herbicides Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE. Algaecide,Algicide,Herbicide,Algaecides,Algicides
D000743 Anemia, Hemolytic A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES). Anemia, Hemolytic, Acquired,Anemia, Microangiopathic,Haemolytic Anaemia,Hemolytic Anemia,Hemolytic Anemia, Acquired,Microangiopathic Hemolytic Anemia,Acquired Hemolytic Anemia,Anaemia, Haemolytic,Anemia, Acquired Hemolytic,Anemia, Microangiopathic Hemolytic,Haemolytic Anaemias,Hemolytic Anemia, Microangiopathic,Microangiopathic Anemia,Microangiopathic Hemolytic Anemias

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