Sam Kacew

Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide.

Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

Criteria for chemical selection for programs on human milk surveillance and research for environmental chemicals

The people of the United States is exposed to a large number of chemicals in their daily lives. In order to prioritize chemicals that should be considered for surveillance of and/or research in human milk, criteria were developed at the Technical Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States. The criteria include (1) lipid solubility and/or persistence in the environment; (2) extensive exposure (e.g., high-production-volume chemicals and chemicals in personal care products); (3) known or suspected toxicity in a biological system; (4) historical interest, trend information; (5) chemicals of emerging concern; and (6) chemicals for medicinal use and chemicals in occupational settings. A working list of chemicals was developed for each of the criteria. It should be noted that more than one criterion may be applicable to a selected chemical, but the selected chemical should possess at least one of these designated criteria. It is hoped that by following a cohort of nursing women through their lactational cycle for a group of these chemicals, data generated will indicate the extent of infant exposure and may suggest methods for risk management to decrease inadvertent exposure for breastfeeding mothers and infants. While not the focus of this article, certain endogenous chemicals in human milk beneficial to the health of the infant warrant study as well.

Human Milk Biomonitoring Data: Interpretation and Risk Assessment Issues

Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children’s neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data exist to state with confidence the link between levels of environmental chemicals in a person’s body and his or her risk of adverse health effects. Human milk biomonitoring presents additional complications. Human milk can be used to obtain information on both the levels of environmental chemicals in the mother and her infant’s exposure to an environmental chemical. However, in terms of the health of the mother, there are little to no extant data that can be used to link levels of most environmental chemicals in human milk to a particular health outcome in the mother. This is because, traditionally, risks are estimated based on dose, rather than on levels of environmental chemicals in the body, and the relationship between dose and human tissue levels is complex. On the other hand, for the infant, some information on dose is available because the infant is exposed to environmental chemicals in milk as a “dose” from which risk estimates can be derived. However, the traditional risk assessment approach is not designed to consider the benefits to the infant associated with breastfeeding and is complicated by the relatively short-term exposures to the infant from breastfeeding. A further complexity derives from the addition of in utero exposures, which complicates interpretation of epidemiological research on health outcomes of breastfeeding infants. Thus, the concept of “risk assessment” as it applies to human milk biomonitoring is not straightforward, and methodologies for undertaking this type of assessment have not yet been fully developed. This article describes the deliberations of the panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on several issues related to risk assessment and human milk biomonitoring. Discussion of these topics and the thoughts and conclusions of the panel are described in this article. We thank the following organizations for generously providing support for the Workshop: the American Chemistry Council; the Centers for Disease Control and Prevention (C13/CCU323635-01); the Department of Health and Human Services, Health Resources and Services Administration (HHSH240200415021P); Health Canada (H405-03-ExSD079/4500078209); 3M; Pennsylvania State University College of Medicine; the Research Foundation for Health and Environmental Effects; and the U.S. Environmental Protection Agency, Office of Children’s Health (CH-83213101-0). The opinions expressed in this article are those of the authors and do not necessarily reflect the views and/or policies of their affiliations.

Conclusions and Recommendations of the Expert Panel: Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States

We thank the following organizations for generously providing support for the workshop: the AmericanChemistry Council; the Centers for Disease Control and Prevention (C13/CCU323635-01); the Departmentof Health and Human Services, Health Resources and Services Administration (HHSH240200415021P);Health Canada (H405-03-ExSD079/4500078209); 3M; Pennsylvania State University College of Medicine;the Research Foundation for Health and Environmental Effects; and the U.S. Environmental ProtectionAgency, Office of Children’s Health (CH-83213101-0).The opinions expressed in this article are those of the authors and do not necessarily reflect the viewsand/or policies of their affiliations.Address correspondence to Cheston M. Berlin, Jr., MD, Department of Pediatrics Children’s Hospital,Milton S. Hershey Medical Center, Pennsylvania State University College of Medi cine, M.C. HO85, PO Box850, Hershey, PA 17033, USA. E-mail: cmb6@psu.edu

Modification by phenobarbital of chlorphenterm1ne‐induced changes in lung morphology and drug‐metabolizing enzymes in newborn rats

Treatment of newborn rat pups with 60 mg/kg.d chlorphentermine for 7 d produced on accumulation of alveolar foam cells accompanied by an increase in relative pulmonary tissue weight. In contrast, administration of 20 mg/kg.d for 1 wk did not markedly alter lung ultrastructure or weight in newborns. Both doses of chlorphentermine elevated the activity of pulmonary aminopyrine N-demethylase but not that of aniline hydroxylase. The increase in relative liver weight was associated with stimulation of the activities of aniline hydroxylase and aminopyrine N-demethylase in newborns administered either chlorphentermine dose. Phenobarbital treatment produced an increase in relative liver weight accompanied by elevated activities of pulmonary aminopyrine N-demethylase and hepatic aniline hydroxylase and aminopyrine N-demethylase. Simultaneous barbiturate and chlorphentermine administration produced stimulation in liver enzymes to the same extent as phenobarbital alone. In contrast, phenobarbital potentiated the chlorphentermine-induced rise in pulmonary aminopyrine N-demethylase. In the case of 60 mg/kg chlorphentermine and barbiturate, the observed potentiation of lung enzyme activity was associated with a reduction in the number of alveolar foam cells. The results suggest that chlorphentermine and phenobarbital stimulate drug-metabolizing enzyme in lung and liver of newborn rats and that phenobarbital may provide protection against phospholipidosis through stimulation of pulmonary, drug-metabolizing enzymes.

Bioavailability to rats of bound [14C] pirimiphos‐methyl in stored wheat

Stored wheat treated with radiolabelled pirimiphos-methyl (0-2-diethyl-amino-6-methyl-pyrimidin-4-yl 0,0-dimethyl phosphorothioate) formed bound (nonextractable) 14C residues. Supercritical fluid extraction, gas chromatography and mass spectrometric techniques were used to identify and quantitate the 14C bound residues in wheat grains. The amount of bound 14C residues present after 28 weeks of storage was about 9.9% of the applied radioactivity. Pirimiphos-methyl accounted for 80% of the bound residue. Grain-bound residues were fed to rats for 5 days. After a total period of 8 days a substantially large percentage of the administered bound 14C residues (72.9%) was eliminated in urine while feces contained only 17.9%. Bound pirimiphos-methyl in wheat grain was metabolized in rats by processes involving hydrolysis, N-dealkylation and 0-demethylation. The results indicate that wheat-bound residues of pirimiphos-methyl are highly bioavailable to the rat and may possess a toxicological potential as manifested by a significant reduction in body weight gain.

Bioavailability in rats of bound pesticide residues from tolerant or susceptible varieties of soybean and canola treated with metribuzin or atrazine

Susceptible or tolerant varieties of soybean treated with metribuzin, or canola treated with atrazine were grown in a controlled environment. Shoots and fruits were harvested at maturity and extracted exhaustively with methanol. The extracted materials containing bound 14C residues were subsequently fed to rats for two days. The elimination of 14C in urine and feces was monitored for 4 days and the distribution of radioactivity in liver, kidney and heart was studied. Higher 14C residues in urine were present in animals fed fruits compared to shoots of soybean or canola of both susceptible and tolerant varieties. The bound atrazine residues from the pods of Atr Tower (tolerant variety of canola) were more bioavailable than Tower (susceptible variety of canola). Bioavailability of bound atrazine from the shoots of canola in both varieties was very low. In soybean fed animals, bound metribuzin derived 14C from the susceptible variety (Maple Amber) was more bioavailable than from the resistant variety (Maple Arrow). However, feeding the animals with susceptible or tolerant varieties of soybean or canola containing bound residues of 14C metribuzin or 14C atrazine for two days did not result in the accumulation of radioactivity in the body organs studied. Thus our data show that the bioavailability of these bound pesticides was dependent on the type of plant parts ingested and the variety of plant species.

Bioavailability of bound 14C residues in rats from bean plants treated with 14C-deltamethrin

Abstract Bean plants were treated with deltamethrin labeled with 14 C at the methyl or benzylic position. The aerial portion of the plants was exhaustively extracted with solvents and the extracted material containing bound 14 C residues was fed to rats. After 4 days 60% and 53% of the dose was excreted in feces and 31% and 20% in the urine from rats fed extracted bean plants treated with deltamethrin labeled at the methyl and benzylic position, respectively. The data demonstrated that bound residues in bean plants treated with deltamethrin may be bioavailable in rats.

Fate of wheat bound malathion residues in rats during gestation.

Malathion [S-1,2-di(ethoxycarbonyl) ethyl 0,0-dimethyl phosphorodithioate], treated wheat when stored for 28 months at 20 degrees C with or without food grade white mineral oil on grains contained about 62 and 79% of the applied insecticide as bound residues, respectively. These bound residues were present mainly in the form of the parent compound. The stored wheat containing bound malathion residues, as well as wheat material freshly spiked with malathion were fed to rats during gestation. No residues of malathion and/or metabolites were detected in urine, feces and body tissues. Further no significant effect on body weight, serum chemistry and cytochrome P450 levels were observed in the mothers. There was no evidence for the histopathological alteration or teratogenic anomalies in the fetuses. However, placental transfer of malathion was indicated by the presence of the insecticide residues in fetuses from rats fed wheat material containing bound residues.

Reappraisal of the use of a single dose of lead for the study of cell proliferation in kidney, liver, and lung

Three days after a single intraperitoneal injection of lead chloride (10 mg/kg) there was a twofold increase in the incorporation of [14C]thymidine into renal DNA. The observed elevation in DNA synthesis was preceded by an enhancement of [14 C]orotic acid incorporation into kidney RNA. In plumbic rats, the concentration of renal cyclic AMP was significantly reduced from day 3 through day 7, while the levels of putrescine, spermidine, and spermine remained generally unchanged throughout the experimental period. As in the case of kidney, lead treatment increased (twofold) orotic acid incorporation into RNA in liver and lung. In contrast, exposure to lead produced a reduction in the amount of thymidine incorporated into hepatic and pulmonary DNA. In both liver and lung, treatment with lead tended to lower the concentrations of three polyamines, putrescine, spermidine, and spermine. While exposure to this nonessential element decreased the level of cyclic AMP in hepatic tissue, a significant rise to 152% of c...