Benzene In Mice Research Articles

Sex difference in the micronucleus induction by benzene in mice

Sex difference in the micronucleus induction by benzene in mice

Trans,trans-Muconic acid, an open-chain urinary metabolite of benzene in mice. Quantification by high-pressure liquid chromatography.

A sensitive h.p.l.c. method is described which separated urinary metabolites from benzene-treated male CD-1 mice. Phenol, trans,trans-muconic acid and quinol in the 48 h urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally administered single dose of benzene (880, 440 and 220 mg/kg body wt.). Catechol occurred in trace amounts. Ascorbic acid was used to adjust urine pH and increase the extraction efficiency of metabolites, especially muconic acid. It allowed an accurate estimation of quinol by preventing its auto-oxidation. trans,trans-Muconic acid was identified and was unique to benzene as none was detected in urine of mice dosed orally with phenol, catechol or quinol (250, 150 and 200 mg/kg, respectively). The potential existence of a toxic benzene metabolite in the form of an aldehyde precursor of muconic acid in vivo is discussed.

Modifications in the myeloclastogenic effect of benzene in mice with toluene, phenobarbital, 3-methylcholanthrene, Aroclor 1254 and SKF-525A

Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase analysis. Male and female CD-1 mice were treated with 2 doses of benzene (440 mg/kg) or toluene (860 or 1720 mg/kg) or both 24 h apart, and sacrificed 30 h (or 54 h) after the first dose. Benzene-treated animals were pretreated with phenobarbital (PB), 3-methylcholanthrene (3-MCA), SKF-525A, or Aroclor 1254. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when the mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment greatly promoted benzene myeloclastogenicity. Females were consistently more resistant to benzene than males. Dose-response curves in benzene-treated mice were much steeper with 3-MCA induction than without. Chromosomal damage was higher with p.o. than i.p. benzeneadministration.

Mechanism of benzene toxicity. Effects of benzene and benzene metabolites on bone marrow cellularity, number of granulopoietic stem cells and frequency of micronuclei in mice

The effects of benzene and benzene metabolites (hydroquinone and catechol) on bone marrow cellularity, number of granulopoietic stem cells and on the frequency of micronuclei in polychromatic erythrocytes were investigated in mice. The dose-effect curve for benzene revealed that there was a threshold dose (approx. 100 mg benzene/kg body wt./day injected subcutaneously on 6 consecutive days) above which severe toxicity occurred in all three parameters. Also hydroquinone gave rise to adverse effects in the parameters studied, but the sequence of occurrence was different from that observed with benzene. These data are interpreted to indicate that hydroquinone is a hemotoxic metabolite of benzene in mice in vivo, but that other metabolites, or benzene itself, also probably contribute to the toxicity. Catechol gave no effects. However, due to acute effects like tremor and convulsions only rather low doses could be tested. Simultaneous administration of toluene dramatically reduced the toxicity of benzene, but gave only a small reduction of the hydroquinone-induced effects.

Toxicological and biochemical effects of repeated administration of benzene in mice.

Repeated dosing of mice with benzene led to a dose-related decrease in red cell production as measured by the incorporation of 59Fe into developing erythrocytes. Phenol, catechol, and hydroquinone were observed in the urine, largely conjugated with glucuronic acid and ethereal sulfate. During repeated dosing, toluene-soluble radioactivity derived from labeled benzene was found to accumulate in blood, liver fat, and, most significantly, bone marrow. Greater accumulation was observed when water-soluble metabolites of benzene were examined in these organs. Covalent binding of benzene metabolites was also observed in liver and marrow during repetitive treatment. Both covalently bound and soluble metabolites accumulated in bone marrow, liver, and kidney over a 24-h period after a single administration of benzene. The highest levels of covalent binding were seen in kidney and liver after 3 d of dosing at 880 mg/kg, two doses per day. Studies in vitro demonstrated the necessity for metabolic activation to produce covalent binding from benzene. These studies demonstrate that increasing benzene toxicity during repetitive treatment of mice is accompanied by increases in the levels of both water-soluble and covalently bound benzene metabolites.

Embryotoxicity of inhaled benzene in mice and rabbits.

The effect of inhaled benzene on embryonal and fetal development was assessed in mice and rabbits. CF-1 mice and New Zealand white rabbits were exposed to 0 or 500 ppm of benzene for 7 hr per day from days 6 through 15 (mice) and 6 through 18 (rabbits) of gestation. Little evidence of maternal toxicity was seen in either species. Although some signs of embryonal toxicity were observed in both mice and rabbits, a teratogenic effect was not discerned in either species inhaling 500 ppm of benzene.

Studies on Poisoning by Benzene and Its Homologues. (11) Strain Difference in Susceptibility to Benzene in Mice

Studies on Poisoning by Benzene and Its Homologues. (11) Strain Difference in Susceptibility to Benzene in Mice

Chromosome aberrations in bone marrow cells after injection of benzene in mice

Chromosome aberrations in bone marrow cells after injection of benzene in mice

Experimental studies on the role of protein nutrition in benzene poisoning of mice.

Two experiments were performed to clarify whether or not the content of casein in the diet changes the susceptibility to benzene in mice. As the indicators for anlysis, the number of leucocyte, hemoglobin content, weights of the thymus, spleen, liver and kidney, and body weight were determined after the repeated subcutaneous injection of benzene with varied doses. Low content of casein in the diet (5%) was proved to decrease the body weight, and the weights of some organs and the administration of benzene decreased the number of leucocyte and weights of the thymus and spleen. Though the influences of benzene administration and of content of casein were certainly addititive on some indicators, such as the weights of thymus and spleen, no significant synergistic influence was observed in all the indicators. Conclusively, it was assumed that there might be the least possibility in increasing of the susceptibility to benzene by the low content of casein in the diet.