The Transplacental Migration and Accumulation in Blood of Volatile Organic Constituents

Dowty, Betty J.; Laseter, John L.; Storer, James S.

doi:10.1203/00006450-197607000-00013

Cited by 127 publications

(36 citation statements)

References 7 publications

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“…The studies designed specifically to investigate developmental effects are limited, primarily because of concomitant exposure to other chemicals, inadequate sample size, and lack of quantification of exposure levels (Budnick, et al, 1984;Goldman, et al, 1985;Heath, 1983;Olsen, 1983). Benzene crosses the human placenta and is present in the cord blood in amounts equal to or greater than those in maternal blood (Dowty, et al, 1976). In a study of subjects with known benzene poisoning in Italy, Forni, et al (1971) reported the case of one pregnant worker exposed to benzene in the air during her entire pregnancy.…”

Section: Developmental Effectsmentioning

confidence: 98%

ATSDR evaluation of health effects of benzene and relevance to public health

et al. 2008

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As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the Toxicological Profile for Benzene. The primary purpose of this article is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of benzene. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.

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Section: Developmental Effectsmentioning

confidence: 98%

ATSDR evaluation of health effects of benzene and relevance to public health

et al. 2008

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“…The exposure is likely to occur from environmental tobacco smoke (Stjenfeldt et al 1986;Homann et al 1989;John et al 1991;Tredaniel et al 1994;Brondum et al 1999;Boetta et al 2000) and combustion emissions, particularly from automobiles (Paustenbach et al 1993;Nordlinder and Jarvholm 1997;Wol 1992). It has been reported that tissue concentrations of benzene in human fetuses of mothers exposed to the compound are comparable to or higher than those in the mothers (Dowty and Laseter 1976). However, not much is known about the health eects of the compound in the immature.…”

Section: Introductionmentioning

confidence: 93%

Comparative metabolism of [ 14 C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

Iba

Ghosal

Snyder

2001

Archives of Toxicology

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Lactating adult female mice treated with a single dose of 880 mg/kg i.p. [14C]benzene, and their 2-day-old sucklings similarly treated or nursed by their treated dams were compared in terms of their ability to metabolize benzene to urinary products or reactive intermediates as assessed by covalently-bound benzene derivatives in whole blood or liver DNA. Six metabolite fractions were identified in the urine of sucklings by high performance liquid chromatographic (HPLC) analysis at 5 h following intraperitoneal (direct) treatment with benzene. Three of the metabolite fractions co-chromatographed with authentic phenol, phenyl glucuronide, and muconic acid, and contributed 11, 6.9 and 0.6%, respectively, to the total urinary benzene metabolites. Two of the fractions were unidentified. The sixth and most polar fraction consisted of multiple metabolites, 21% of which were conjugates, and accounted for 72% of the total urinary metabolites. A similar metabolite profile was observed in 24-h urine samples from treated dams with the exception that one of the unidentified fractions in the sucklings was absent and levels of the metabolites were quantitatively higher than those observed in sucklings 5 h following their treatment with benzene. Furthermore, 78% of the most polar fraction from the dams consisted of conjugates compared with 21% of that from the sucklings. The metabolite pattern in urine of sucklings nursed by treated dams was qualitatively similar to, but quantitatively different from the pattern in treated dams. Five hours following intraperitoneal treatment with benzene, covalent binding of the compound to DNA (expressed as pmol benzene equivalents/mg DNA) in sucklings was slightly higher in whole blood (1.15+/-0.07) than in liver (0.77+/-0.07), whereas in the dam, it was slightly lower in whole blood (0.88+/-0.48) than in liver (1.63+/-0.61). Twenty four hours following benzene exposure in sucklings of benzene-treated dams, DNA binding by the compound in whole blood (3.85+/-1.05) and liver (0.11+/-0.03) was higher and lower, respectively than the binding observed in benzene-injected sucklings 5 h following the injection. Our results show that excretable as well as reactive metabolites of benzene are formed substantially by the neonatal mouse, and that the extent of bioactivation of the compound is comparable in the adult and the suckling mouse. The results show also that sucklings of benzene-exposed mothers are exposed to substantial levels of the compound and are potentially susceptible to its toxic effects.

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“…Using a mass-spectrometric method, Dowty, Laseter, and Storer (1976) demonstrated MIBK in human maternal blood samples collected immediately after delivery. The authors interpreted this finding as indicating the potential for MIBK to enter the umbilical cord and cross the placenta.…”

Section: Distributionmentioning

confidence: 99%

Safety Assessment of MIBK (Methyl Isobutyl Ketone)1

Johnson¹

2004

Int J Toxicol

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MIBK (Methyl Isobutyl Ketone) is an aliphatic ketone that functions as both a denaturant and solvent in cosmetic products. Current use in cosmetic products is very limited, but MIBK is reported to be used in one nail correction pen (volume = 3 ml) at a concentration of 21%. The maximum percutaneous absorption rate in guinea pigs is 1.1 µmol/min/cm 2 at 10 to 45 min. Metabolites include 4-hydroxy-4-methyl-2-pentanone (oxidation product) and 4-methyl-2-pentanol (4-MPOL) (reduction product). Values for the serum half-life and total clearance time of MIBK in animals were 66 min and 6 h, respectively. In clinical tests, most of the absorbed MIBK had been eliminated from the body 90 min post exposure. MIBK was not toxic via the oral or dermal route of exposure in acute, short-term, or subchronic animal studies, except that nephrotoxicity was observed in rats dosed with 1 g/kg in a short-term study. MIBK was an ocular and skin irritant in animal tests. Ocular irritation was noted in 12 volunteers exposed to 200 ppm MIBK for 15 min in a clinical test. A depression of the vestibulo-oculomotor reflex was seen with intravenous infusion of MIBK (in an emulsion)at 30 µM/kg/min in female rats. The no-observed-effect level in rats exposed orally to MIBK was 50 mg/kg. Both gross and microscopic evidence of lung damage were reported in acute inhalation toxicity studies in animals. Short-term and subchronic inhalation exposures (as low as 100 ppm) produced effects in the kidney and liver that were species and sex dependent. Dermal doses of 300 or 600 mg/kg for 4 months in rats produced reduced mitotic activity in hair follicles, increased thickness of horny and granular cell layers of the epidermis, a decrease in the number of reactive centers in follicles (spleen), an increase in the number of iron-containing pigments in the area of the red pulp (spleen), and a reduction in the lipid content of the cortical layer of the adrenal glands. Neuropathological changes in the most distal portions of the tibial and ulnar nerves were observed in young adult rats which inhaled 1500 ppm MIBK for up to 5 months. No adverse effects were seen in any other neurological end point by any route of exposure in other studies using rats or other animal species. Clinical tests demonstrated a threshold for MIBK-induced irritation of the lungs at 0.03 to 0.1 mg/L after 1 min of respiration. MIBK was not mutagenic in the Ames test or in a mitotic gene-conversion assay in bacteria. Mammalian mutagenicity test results were also negative in the following assays: mouse lymphoma, unscheduled DNA synthesis, micronucleus, cell transformation, and chromosome damage. MIBK did not induce any treatment-related increases in embryotoxicity or fetal malformations in pregnant Fischer 344 rats or CD-1 mice that inhaled MIBK at concentrations of 300, 1000, or 3000 ppm. There was evidence of treatment-related maternal toxicity only at the highest concentration tested. MIBK applied to the tail of rats daily at doses of 300 or 600 mg/kg for 4 months produced changes in the t...

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The Transplacental Migration and Accumulation in Blood of Volatile Organic Constituents

Cited by 127 publications

References 7 publications

ATSDR evaluation of health effects of benzene and relevance to public health

ATSDR evaluation of health effects of benzene and relevance to public health

Comparative metabolism of [ 14 C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

Safety Assessment of MIBK (Methyl Isobutyl Ketone)1

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