NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-butyl phthalate

Kavlock, Robert J.; Boekelheide, Kim; Chapin, Robert E.; Cunningham, Michael L.; Faustman, Elaine M.; Foster, Paul M.D.; Golub, Mari S.; Henderson, Rogene F.; Hinberg, Irwin; Little, Ruth E.; Seed, Jennifer; Shea, Katherine M.; Tabacova, Sonia; Tyl, Rochelle W.; Williams, Paige L.; Zacharewski, Timothy R.

doi:10.1016/s0890-6238(02)00033-3

Cited by 155 publications

(77 citation statements)

References 56 publications

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“…Cumulative exposures to other endocrine active phthalates within the same order of magnitude are likely. Therefore, both the Risk Assessment Report of the European Chemical Bureau (ECB, 2004a) and the NTP-CERHR report on DnBP (Kavlock et al, 2002a) might need to be updated to the most recent findings in the fields of exposure assessment, toxicology and epidemiology. Figure 2.…”

Section: Discussionmentioning

confidence: 99%

“…DnBP is used in the adhesive industry for latex and polyvinyl acetate (PVA) emulsions and as a solvent or additive in inks and dyes, sealants/grouting agents, nitrocellulose paints, film coatings and glass fibres. Fulfilling multiple purposes, DnBP is used in various consumer products like perfumes, pesticides, aerosol sprays, skin emollients and nail polishes (Kavlock et al, 2002a;ECB, 2004a;EFSA, 2005a). In the pharmaceutical field it is used in the gastric juice-resistant coating of capsules both in the US and Europe (Koch et al, 2005a;FDA, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Di-n-butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children

Koch

Becker

Wittassek

et al. 2006

J Expo Sci Environ Epidemiol

139

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We analysed urine samples from the 2001/2002 pilot study of the German Environmental Survey on Children (GerES IV) for the concentrations of the di-n-butylphthalate (DnBP) metabolite mono-n-butylphthalate (MnBP) and the butlybenzylphthalate (BBzP) metabolite mono-benzyl-phthalate (MBzP). The study population consisted of 239 children (106 boys, 133 girls) aged between 2 and 14 years (median 8.5 years). We applied two calculation models to estimate the daily intake for the two parent phthalates from metabolite excretion. One was based on the creatinine-related metabolite concentrations; the other was based on the volume-related metabolite concentrations. Median urinary metabolite concentrations were 174 mg/l (136 mg/g creatinine) for MnBP and 19.7 mg/l (15.3 mg/g creatinine) for MBzP. Such levels have been determined in German children before. Compared to the USA, German median MnBP levels were about 3-10 times higher, whereas MBzP levels were in the same range. Median daily intakes calculated with the creatinine-based model were 4.07 (range: 0.66-76.4; 95th percentile: 14.9) mg/kg body weight (bw)/day for DnBP and 0.42 (range: 0.06-13.9; 95th percentile: 2.57) mg/kg bw/day for BBzP. Daily intakes calculated with the volume-based model were approximately two times higher with a median of 7.61 (range: 0.91-110; 95th percentile: 30.5) mg/kg bw/day for DnBP and a median of 0.77 (range: 0.05-31.3; 95th percentile: 4.48) mg/kg bw/day for BBzP. Using the creatinine model, 28 (11.7%) of the 239 children exceeded the TDI for DnBP of 10 mg/kg bw/day defined by the European Union. Employing the volume model, 89 (37.2%) children exceeded the TDI. For BBzP, no preventive limit values (TDI or RfD) were exceeded. For both phthalates and independent of the model, we found increasing daily intakes with decreasing age. Between 25% (creatinine model) and 50% (volume model) of the 2-4-year old children had daily intakes for DnBP above the TDI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Di-n-butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children

Koch

Becker

Wittassek

et al. 2006

J Expo Sci Environ Epidemiol

139

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“…Humans are exposed to phthalic acid esters from food that may be contaminated during the crop's growth, processing, storage and packaging, as well as exposure to air (Kavlock et al 2002). Phthalic acid esters have also been detected in human urine and milk samples (Brock et al 2002;Zhu et al 2006).…”

Section: Effect Of Phthalic Acid Esters On Human Healthmentioning

confidence: 99%

Contamination and remediation of phthalic acid esters in agricultural soils in China: a review

He¹,

Gielen²,

Bolan³

et al. 2014

Agron. Sustain. Dev.

230

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Phthalic acid esters have been used as plasticizers in numerous products and classified as endocrine-disrupting compounds. As China is one of the largest consumers of phthalic acid esters, some human activities may lead to the accumulation of phthalic acid esters in soil and result in contamination. Therefore, it is necessary for us to understand the current contamination status and to identify appropriate remediation technologies. Here, we reviewed the potential sources, distribution, and contamination status of phthalic acid esters in soil. We then described the ecological effect and human risk of phthalic acid esters and finally provided technologies to remediate phthalic acid esters. We found that (1) the application of plastic agricultural films, municipal biosolids, agricultural chemicals, and wastewater irrigation have been identified as the main sources for phthalic acid ester contamination in agricultural soil; (2) the distribution of phthalic acid esters in soils is determined by factors such as anthropogenic behaviors, soil type, properties of phthalic acid esters, seasonal variation, etc.; (3) the concentrations of phthalic acid esters in soil in most regions of China are exceeding the recommended values of soil cleanup guidelines used by the US Environmental Protection Agency (US EPA), causing phthalic acid ester in soils to contaminate vegetables; (4) phthalic acid esters are toxic to soil microbes and enzymes; and (5) phthalic acid ester-contaminated soil can be remedied by degradation, phytoremediation, and adsorption.

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“…Di-n-butyl phthalate (DBP), a representative of phthalate acid esters (PAEs) that have been used in a wide variety of industrial and common household products, can induce the atrophy in the testes and seminiferous tubules, reproductive tract malformation, the change in enzyme activity in testicular cells, hormone reduction, spermatogenic cell apoptosis and sperm counts reduction (Kavlock et al, 2002;Shultz et al, 2001; M. S. Alam et al, 2010a; M. S. Alam et al, 2010b). Benzo(a)pyrene (Bap), a prototype of polycyclic aromatic hydrocarbon (PAH) that is released into the environment by industrial emission, has attracted worldwide attention as its toxic effect on male reproduction.…”

Section: Introductionmentioning

confidence: 99%

Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

Huang¹,

Chen²,

Shu

2014

GEP

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Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a suppressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between haploid and tetraploid. These effects were more obvious in the combined group. Furthermore, the expression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.

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NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-butyl phthalate

Cited by 155 publications

References 56 publications

Di-n-butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children

Di-n-butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children

Contamination and remediation of phthalic acid esters in agricultural soils in China: a review

Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

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