Human exposure breast milk

Once released into the environment, phthalates degrade rapidly the half-life of DEHP (the most widely used phthalate) in water is only 2-3 weeks. But in air, or when bound to soil, phthalates can be stable for longer periods of time. The reported levels of DEHP, the most common phthalate, in air, water, and soil (see Table 7.6) illustrate this. As with other EDCs, phthalates are also ubiquitous in the environment and are present in the human body, breast milk, blood, and urine. In one study, over 75% of the US population were found to have phthalate metabolites in the urine (Stahlhut et al., 2007). This is hardly a surprise as the available data suggests life-long human exposure to occur from in utero through death of individuals. 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

The available evidence suggests that excretion of methyl parathion metabolites in humans and animals following acute oral exposure is essentially the same and occurs rapidly. Excretion occurs primarily via the urine. Methyl parathion can also be excreted in breast milk, although it has been detected only in a limited number of samples from women of central Asia, for which exposure data were not available (Lederman 1996) (see also Section 3.4.2.2). A study in rats also reported excretion of methyl parathion in the milk (Golubchikov 1991 Goncharuk et al. 1990). 

The developing human s source of nutrition changes with age from placental nourishment to breast milk or formula to the diet of older children who eat more of certain types of foods than adults. A child s behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Public concern about PBDE levels in the environment was heightened when it was shown that a sharp increase in the concentration of certain PBDEs had occurred in human breast milk over only a 10-year period (Meironyte et al. 1999 Noren and Meironyte 2000), and the levels of exposure in some infants and toddlers were similar to those shown to cause developmental neurotoxicity in animal experiments (Costa and Giordano 2007). As a result of these concerns, the majority of commercial PBDE mixtures have been banned from manufacture, sale, and use within the European Union. 

Several studies of tissue distribution in humans after inhalation exposure to trichloroethylene report levels in the blood (Astrand and Ovrum 1976 Monster et al. 1976 Muller et al. 1974). Once in the bloodstream, trichloroethylene may be transported rapidly to various tissues where it will likely be metabolized. Trichloroethylene was detected in the blood of babies at birth after the mothers had received trichloroethylene anesthesia (Laham 1970), and detectable levels (concentrations not reported) have been found in the breast milk of mothers living in urban areas (Pellizzari et al. 1982). Post-mortem analyses of human tissue from persons with unspecified exposure revealed detectable levels of trichloroethylene (<1-32 pg/kg wet tissue) in most organs (McConnell et al. 1975). The relative proportions varied among individuals, but the major sites of distribution appeared to be body fat and the liver. 

Exposure Levels in Humans. This information is necessary for assessing the need to conduct health studies on these populations. Trichloroethylene has been detected in human body fluids such as blood (Brugnone et al. 1994 Skender et al. 1994) and breast milk (Pellizzari et al. 1982). Most of the monitoring data have come from occupational studies of specific worker populations exposed to trichloroethylene. More information on exposure levels for populations living in the vicinity of hazardous waste sites is needed for estimating human exposure. 

The main route of excretion is via the faeces (biliary excretion), urine and breast-milk. Excretion through breast-milk results in transfer to breastfed infants, who therefore are highly exposed. There is also transfer across the placenta, thus causing fetal exposure. Perinatal exposure is a major concern with regard to human health effects, even at present background exposure levels. 

No information is available as to whether w-hexane or its metabolites cross the placenta in humans. Transfer across the placenta has been demonstrated in rats for -hexane and two resulting metabolites, 2-hexanone and 2,5-hexanedione (Bus et al. 1979) no preferential distribution to the fetus was observed for either -hexane or the metabolites. Due to its relatively rapid metabolism, storage of -hexane in body fat does not appear to occur at air concentrations to which humans are exposed thus, there is unlikely to be mobilization of maternally stored -hexane upon pregnancy or lactation. -Hcxanc has been detected in samples of human breast milk (Pellizzari et al. 1982) however, -hexane was not quantified, nor was any attempt made to assess the subjects exposure. A human milk/blood partition coefficient of 2.10 (Fisher et al. 1997) indicates there would be preferential distribution to this compartment if significant absorption occurred however no pharmacokinetic experiments have been... 

There is no experimental evidence available to assess whether the toxicokinetics of -hexane differ between children and adults. Experiments in the rat model comparing kinetic parameters in weanling and mature animals after exposure to -hexane would be useful. These experiments should be designed to determine the concentration-time dependence (area under the curve) for blood levels of the neurotoxic /7-hcxane metabolite 2,5-hexanedione. w-Hcxanc and its metabolites cross the placenta in the rat (Bus et al. 1979) however, no preferential distribution to the fetus was observed. -Hexane has been detected, but not quantified, in human breast milk (Pellizzari et al. 1982), and a milk/blood partition coefficient of 2.10 has been determined experimentally in humans (Fisher et al. 1997). However, no pharmacokinetic experiments are available to confirm that -hexane or its metabolites are actually transferred to breast milk. Based on studies in humans, it appears unlikely that significant amounts of -hexane would be stored in human tissues at likely levels of exposure, so it is unlikely that maternal stores would be released upon pregnancy or lactation. A PBPK model is available for the transfer of M-hcxanc from milk to a nursing infant (Fisher et al. 1997) the model predicted that -hcxane intake by a nursing infant whose mother was exposed to 50 ppm at work would be well below the EPA advisory level for a 10-kg infant. However, this model cannot be validated without data on -hexane content in milk under known exposure conditions. 

Exposure Levels in Humans. The database for -hexane exposure levels in humans is limited to a few older detections of -hexane in breast milk and determinations of levels in body fluids and alveolar air collected in foreign countries. A more current and complete database would be helpful in determining the current exposure levels, thereby permitting the estimation of the average daily dose associated with various scenarios (e.g., living near a hazardous waste site). Since -hexane is rapidly metabolized within the human body, further studies correlating levels in the environment with the levels of metabolites and biomarkers in humans would be helpful. This information is necessary for assessing the need to conduct health studies on these populations. 

Endrin has been detected in human breast milk (0.02-6.24 milligrams endrin in each kilogram milk fat [mg/kg]) this may be a route of exposure for nursing infants. However, no studies of endrin in breast milk in United States or Canadian populations have been conducted. 

Exposure Levels in Humans. Metabolism of endrin in humans is relatively rapid compared with other organochlorine pesticides. Thus, levels in human blood and tissue may not be reliable estimates of exposure except after very high occupational exposures or acute poisonings (Runhaar et al. 1985). Endrin was not found in adipose tissue samples of the general U.S. population (Stanley 1986), or in adipose breast tissue from breast cancer patients in the United States (Djordjevic et al. 1994). Endrin has been detected in the milk of lactating women (Alawi et al. 1992 Bordet et al. 1993 Dewailly et al. 1993), but no data from the United States could be located. Data on the concentrations of endrin in breast milk from U.S. women would be useful. No information was found on levels of endrin, endrin aldehyde, or endrin ketone in blood and other tissues of people near hazardous waste sites. This information is necessary for assessing the need to conduct health studies on these populations. 

Exposure Levels in Humans. Heptachlor epoxide has been detected in human blood, tissues (including adipose tissue), and breast milk (Al-Omar et al. 1986 Holt et al. 1986 Larsen et al. 1971 Savage et al. 1981). The presence of heptachlor epoxide is used as an indicator of exposure to heptachlor. Current monitoring studies of heptachlor epoxide in these tissues and fluids would be helpful in assessing the extent to which populations, particularly in the vicinity of hazardous waste sites, have been exposed to heptachlor. 

It is not possible to achieve "adequate control" of the risks of persistent, bioaccumulative chemicals. The fact that traditional risk assessment cannot reasonably be applied to such chemicals, and that a revised PBT (persistent, bioaccumulative, toxic) assessment is necessary, is explicitly recognised in the EU s Technical Guidance Document for risk assessment. Their intrinsic properties mean that there is a high risk of exposure at sometime during the lifecycle of the chemical or the article that contains it. Even small releases, if they are continuous, can result in significant exposures. This is why we see significant and, in some cases, escalating levels of brominated flame retardants, nonylphenols and other persistent chemicals in breast milk, umbilical cord blood and human tissue. 

To evaluate human exposure to phthalates and their substitutes, the main approaches investigate either the levels of chemicals in matrices relevant for human exposure (indoor air, dust, food and packages, etc.) or the levels of parent and metabolite compounds in human samples (serum, urine, or breast milk). An overview of phthalate and nonphthalate plasticizers together with their metabolites commonly reported in literature is presented in Table 5. The half-lives for the most of these compounds are already established and therefore, by evaluating the levels of their metabolites in human urine, the levels of their parent compounds may be... 

Exposure of humans to perchlorate via foodstuffs and drinking water has been documented [241]. Urine, breast milk, amniotic fluid, saliva, and blood have been used as matrices in biomonitoring of human exposures to perchlorate [233, 242-253] (Table 10). Assessment of human exposures to perchlorate is important, since this compound blocks iodine uptake in the thyroid gland, which can lead to a decrease in the production of thyroid hormones (T3 and T4) essential for neurodevelopment [260]. 

Breast milk During lactation human mammary tissue expresses the sodium iodide symporter [260], and thus significant transfer of perchlorate into human milk is likely. The presence of micrograms per liter concentrations of perchlorate in milk collected fi om US women [233] confirms lactation as a relevant perchlorate excretion path. If lactating women are secreting perchlorate in milk, then urine-based estimates of total perchlorate exposure for these individuals are likely to be lower than actual [242]. 

Hogberg J, Hanherg A, Berglund M, Skerfving S, Remherger M, Calafat AM, Filipsson AF, Jansson B, Johansson N, Appelgren M, Hakansson H (2008) Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ Health Perspect 116 334—339... 

No studies were located regarding the tissue distribution of 1,4-dichlorobenzene in humans after inhalation exposure to 1,4-dichlorobenzene. The compound has been found, however, in human blood, fatty tissue, and breast milk, presumably as a result of exposure via inhalation. In a study of Tokyo residents, detectable levels of 1,4-dichlorobenzene were found in all of 34 adipose tissue samples and all of 16 blood samples tested (Morita and Ohi 1975 Morita et al. 1975). In a national survey of various volatile organic compounds (VOC) found in composites of human adipose tissue, samples were collected from persons living in the nine geographic areas that comprise the United States (within this survey). 

Distribution. Quantitative inhalation, oral, or dermal distribution studies in humans are not available for 1,4-dichlorobenzene. 1,4-Dichlorobenzene has been detected in human blood, adipose tissue, and breast milk after an assumed inhalation exposure in Tokyo residents (Morita and Ohi 1975 Morita et al. 1975), as well as people in some parts of the United States (EPA 1983b, 1986). The available data indicate that after inhalation, oral, and subcutaneous exposure, 1,4-dichlorobenzene preferentially distributes to the fat tissue and organ-specific sites within the body (Hawkins et al. 1980), following the order adipose > kidney > liver > blood (Charboimeau et al. 1989b Hawkins et al. 1980). Although... 

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