Phthalate esters exposure

Environ. Health PerspecL, 105 (Suppl. 1), 243-244 Nielsen, J., Akesson, B. Skerfving, S. (1985) Phthalate ester exposure—air levels and health of workers processing polyvinylchloride. Am. ind. Hyg. Assoc. J., 46, 643-647... 

Yoshimura, M. Inoue, K. Hanaoka, T. Pan, G. Takahashi, K. Yamano, Y. Iwasaki, Y. Ito, R. Saito, K. Tsugane, S. Nakazawa, H. Development of simultaneous determination method of phthalate monoester metabolites in urine by LC/MS/MS and its application to assessment of phthalate-ester exposure. Bunseki Kagaku 2006, 55, 661. 

In Franco et al. [15] it is concluded that the characterization models, like EUSES and ACC-human, underestimate human exposure to phthalate esters because they consider only a few key pathways. It is not known whether the more relevant pathways for phthalate esters are taken into account in the Usetox model ... 

Franco A, Prevedouros K, Alii R, Cousins IT (2007) Comparison and analysis of different approaches for estimating the human exposure to phthalate esters. Environ Int 33(3) 283—291... 

From the wide variety of emerging pollutants of industrial origin that could be considered here, bisphenol A (BPA) and phthalate esters (PE) are of especial relevance not only because of the high volumes produced and their widespread use, but also because of their demonstrated toxicity, particularly as endocrine disrupters. Both of them have been included in the final report of the European Commission toward the establishment of a priority list of endocrine disrupter chemicals, EDCs [3], and have been rated as of high risk of exposure for human and wildlife populations. Because of their structural characteristics these compounds cannot be included in any of the groups described above, so they will be described in this section (see Fig. 10). 

Di-tt-octylphthalate has been shown to be a mild liver toxin at high doses in acute- and intermediate-duration studies in rodents. While the mechanism of action for these hepatic effects is not known, di-w-octylphthalate does not appear to behave like other phthalate esters such as di(2-ethylhexyl)phthalate, which have been shown to be hypolipidemic peroxisome proliferators. Instead, the liver changes associated with exposure to di- -octylphthalate are characterized by marked centrilobular accumulation of fat and loss of glycogen, accompanied by reduced glucose-6-phosphatase activity and some centrilobular necrosis. 

Studies in animals suggest that, unlike some other phthalate esters, the potential for adverse reproductive or developmental effects following exposure to di-n-octylphthalate by the route most relevant to human exposure (oral) is very low (Foster et al. 1980 Gray and Butterworth 1980 Hardin et al. 1987 Heindel et al. 1989 Mann et al. 1985 Morrissey et al. 1989 NIOSH 1983 NTP 1985 Oishi 1990 Oishi and Hiraga 1980). Therefore, it does not appear that individuals of child-bearing age or embryos/fetuses are likely to be unusually susceptible to the effects of di-n-octylphthalate. No other information is available on populations with above-average susceptibility to di-n-octylphthalate. 

Reproductive Toxicity. No studies were located regarding reproductive effects in humans or animals following inhalation or dermal exposure to di-ft-octylphthalate. No studies were located in humans following oral exposure to this compound. Di-u-octylphthalate caused significant decreases in human sperm motility in vitro (Fredricsson et al. 1993). The results of several acute- and intermediate-duration oral studies in rodents indicate that the potential of di-w-octylphthalate to cause adverse reproductive effects is low. Unlike other phthalate esters such as di(2-ethylhexyl)phthalate, di-w-octylphthalate does not appear to adversely affect testicular function or morphology (Foster et al. 1980 Gray and Butterworth 1980 Heindel et al. 

Perwak, Goyer M, Schimke G, et al. 1980. An exposure and risk assessment for phthalate esters. Final draft report. Washington, DC U.S. Environmental Protection Agency, Office of Water and Waste Management. 

Although the metabolism of several phthalate esters has been studied in vitro, essentially all of the in vivo studies have involved DEHP. A summary of these experiments which involved exposure offish to aqueous - C-DEHP is presented in Table IV (11,12). Tissue C was isolated and separated into parent and the various metabolites by preparative thin layer chromatography on silica gel. Metabolites were hydrolyzed where appropriate and identified by gas chromatography-mass spectroscopy. In whole catfish, whole fathead minnow and trout muscle, the major metabolite was the monoester while in trout bile the major metabolite was the monoester glucuronide. The fact that in all cases the major metabolite was monoester or monoester glucuronide despite the differences in species, exposure level and duration, etc. represented by these data, suggests that hydrolysis of DEHP to monoester is important in the biotransformation of DEHP by fish. 

Foster PM (2006) Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 29 140-147... 

David RM (2000) Exposure to phthalate esters. Environ Health Perspect 108 A440... 

Benzene is a volatile, colorless, highly flammable liquid that is consumed as a raw material for the manufacture of phenolic and polyester resins, polystyrene plastics, alkylbenzene surfactants, chlorobenzenes, insecticides, and dyes. It is hazardous both for its ignitability and toxicity (exposure to benzene causes blood abnormalities that may develop into leukemia). Naphthalene is the simplest member of a large number of multicychc aromatic hydrocarbons having two or more fused rings. It is a volatile white crystalline solid with a characteristic odor and has been used to make mothballs. The most important of the many chemical derivatives made from naphthalene is phthalic anhydride, from which phthalate ester plasticizers are synthesized. 

DEHP exposure of humans might result from intravenous administration of blood that has been stored in plastic containers, or through hemodialysis. Under situations such as these, in which DEHP is introduced directly into the blood, it is possible to evaluate exposure by measuring blood DEHP concentrations. DEHP metabolites, MEHP and phthalic acid, are also measured in the blood to determine exposure from medical products or devices (Barry et al. 1989 Sjoberg and Bondesson 1985). If the total amount of phthalate is to be monitored, the phthalate esters are first de-esterified (Liss et al. 1985). Techniques that measure total phthalic acid are not specific for DEHP exposure since other alkyl phthalic acid esters that are used as plasticizers will also produce phthalic acid after de-esterification. 

Limited information was located regarding possible interactions of DEHP with other chemicals in humans. Urinary measurements of the monoester metabolites of seven common phthalates in 289 adults from the U.S. population, determined using the selective and sensitive analytical approach discussed in Section 3.8.1 (Biomarkers Used to Identify or Quantify Exposure to DEHP), showed detectable levels of monoethyl phthalate (95th percentile concentration, 3,750 ppb), monobutyl phthalate (294 ppb), monobenzyl phthalate (137 ppb), 2-ethylhexyl phthalate (21.5 ppb), cyclohexyl phthalate (8.6 ppb), isononyl phthalate (7.3 ppb), and octyl phthalate (2.3 ppb), reflecting exposure to DEHP, dibutyl phthalate, benzyl butyl phthalate, di-(2-ethylhexyl) phthalate, dicyclohexyl phthalate, di-isononyl phthalate, and dioctyl phthalate, respectively (Blount et al. 2000a). Considering evidence such as this which indicates that co-exposure to multiple phthalates can occur, as well as the likelihood that many of these compounds exert effects via a common mechanism of action, there is a potential for interactions between DEHP and other phthalate esters. 

EPA. 1980b. An exposure and risk assessment for phthalate esters. Washington, DC U.S. Environmental Protection Agency. 

All phthalate esters are readily absorbed, but toxicokinetics vary based on the route of exposure. Once absorbed, they are quickly distributed to organs and other body tissues such as the liver (bile) or kidneys. Phthalate esters metabolize quickly to a monoester but do not progress further. From 4.5% to 15% of single doses of 10-30 g of DEHP are excreted as metabolites in the urine of man. 

ACD is a skin reaction resulting from contact dermal contact with allergens. ACD progresses in two phases. Sensitization is acquired in the initial phase. In the second phase, subsequent exposure elicits an inflammatory reaction. F°1 Large numbers of chemical compounds are known to cause ACD. These include acrylates, aldehydes, amines, anhydrides, etha-nolamines, formaldehyde, resins, metals, pesticides, phenols, phthalate esters, preservatives, isocyanates, solvents, and others. Table 27.4 contains a partial list of these. A more complete list can be found on the webJ21l... 

To monitorize the exposure of workers OSHA and NIOSH have developed some analytical procedures for the determination of phthalate esters in workers environment. In NIOSH method 5020.2, DBP and DEHP are sampled from air with a 0.8-/rm cellulose ester membrane and... 

Clark, K., Cousins, I. T., and Mackay, D., Assesment of critical exposure pathways. In The Handbook of Environmental Chemistry, Part Q, Phthalate Esters, Vol. 3, Staples, C. A., Ed., Springer-Verlag, Berlin, 2003. 

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