Phthalates demonstrate genotoxicity on human mucosa of the upper aerodigestive tract

Kleinsasser, Norbert; Kastenbauer, E.; Weissacher, Herbert; Muenzenrieder, Ruth K.; Harréus, Ulrich

doi:10.1002/(sici)1098-2280(2000)35:1<9::aid-em2>3.0.co;2-1

Cited by 69 publications

(27 citation statements)

References 16 publications

(16 reference statements)

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“…Using the alkaline comet assay, researchers have found evidence of genotoxicity with in vitro studies examining lymphocytes and mucosal cells of the upper aerodigestive tract after exposure to DBP and DiBP (Kleinsasser et al 2000a(Kleinsasser et al , 2000b(Kleinsasser et al , 2001. In another study using the alkaline comet assay on human leukocytes, an association between MEHP and DEHP and increased tail moments was found (Anderson et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Recent in vitro studies using the alkaline comet assay (single-cell gel electrophoresis) found di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP) to be genotoxic in human epithelial cells of the upper aerodigestive tract (Kleinsasser et al 2000a), as well as in mucosal cells and lymphocytes (Kleinsasser et al 2000b). Additionally, the comet assay was used to detect DNA damage in human lymphocytes induced by in vitro exposure to DEHP and MEHP (Anderson et al 1999).…”

Section: Volume 111 | Number 9 | July 2003 • Environmental Health Permentioning

confidence: 99%

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The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

Duty¹,

Singh²,

Silva³

et al. 2003

Environ Health Perspect

268

145

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Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.

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Section: Discussionmentioning

confidence: 99%

Section: Volume 111 | Number 9 | July 2003 • Environmental Health Permentioning

confidence: 99%

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

Duty¹,

Singh²,

Silva³

et al. 2003

Environ Health Perspect

268

145

View full text Add to dashboard Cite

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“…Kleinsasser et al reported, using an in vitro comet assay, that DNA damage (single-strand breaks) was signifi cantly induced by DIBP (354μmol/mL) in human oropharyngeal and nasal mucosa (32). In further work, Kleinsasser et al found that DIBP induced strand breaks in DNA, in both blood lymphocytes and normal mucosal cells from the oropharynx or larynx of patients of head and neck cancer (33).…”

Section: Discussionmentioning

confidence: 99%

Ovarian development in Wistar rat treated prenatally with single dose diisobutyl phthalate

Ray¹,

D’Souza²,

Kumar³

et al. 2013

BLL

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Abstract:Phthalates are a class of industrial compounds with an array of toxicological properties used in day to day life. Diisobutyl phthalate on (DIBP) is used as an additive to keep the plastics soft or fl exible (plasticizer) in nitrocellulose plastic, nail polish, explosives, lacquer manufacturing etc. Although DIBP exposure in humans is generally low, people in adhesive industries and pharmaceutical industries are exposed to higher levels. The aim of this study was to determine the effect of single dose of DIBP on developing ovary of Wistar rat. One hundred and eight adult pregnant Wistar rats were divided into control and experimental groups. Rats in experimental group were given DIBP on day 10, 12 and 14 of gestation at 0.375, 0.75 and 1.25 ml/kg body weight dose intraperitoneally in a single dose. Sections of ovaries collected on day 21 of gestation were stained with hematoxylin and eosin and examined and Masson's trichrome histologically. Sections belonging to the control group showed the presence of oocytes in clusters separated by thin fi brous septa. Degeneration oocytes, empty follicles surrounded by follicular cells without gonocytes in the center were observed in ovarian stroma. Blood vessels in the ovarian stroma were prominent and congested. Around a bunch of follicles total architectural disarray was observed although on special staining fi brosis was not evident. As pregnant women are constantly exposed, effect of DIBP on ovary of a developing fetus would denote the long term consequence in future generations (Fig. 5, Ref. 39 Phthalates are a class of widely used industrial compounds known technically as dialkyl or alkyl aryl esters of 1, 2-benzenedicarboxylic acid. The common forms of phthalates are Diethyl hexyl phthalate (DHEP), Diallyl phthalates (DAP), Di-n-propyl phthalates (DPP), Di-n-butyl phthalates (DBP), and Diisobutyl phthalates (DIBP).Phthalates with a variety of toxicological properties are used in day to day life. These phthalates are nearly omnipresent in modern society and are found in the plastic items, vinyl fl ooring, wall coverings, lubricants, adhesives, detergents, nail polish, hair spray and car wash (1).The adverse effects produced by phthalates are changes in morphology, physiology, growth, development or life span of an organism which results in an impairment of functional capacity and ability to compensate for additional stress (2). Diisobutyl phthalateDIBP (phthalic acid ,di isobutyl ester 1,2-benzenedicarboxylic acid ,bis-(2-methyl propyl) ester di-(isobutyl)-1,2-benzene dicarboxylate) is the branched isomer of DBP and an additive used to keep the plastics soft or more fl exible (plasticizer) often in combination with other phthalates. DIBP is used in nitrocellulose plastic, nail polish, explosive materials, lacquer manufacturing, consumer products, blood bags, pharmaceuticals and automobile parts. They are ubiquitous in our environment and most people including pregnant women and their fetuses are exposed to multiple phthalates at a time. Saillenfait et al estim...

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“…Some environmental estrogenic compounds including BPA, 4-NP, 4-t-OP, and their ethoxylates, have shown mutagenic effects in in vitro or in vivo assays [51][52][53][54][55][56]. Phthalate compounds, including dibutyl phthalate, diisobutyl phthalate, bis (2-ethylhexyl) phthalate, and mono-2-ethylhexyl phthalate, have potential mutagenic and carcinogenic effects on organisms and trick a possible pathway of tumor initiation in animals [57][58][59][60][61]. Aniline is nonmutagenic [62][63][64], but its derivates such as 2,4-dimethylaniline and 2,4,6-trimethylaniline were identified as mutagens and carcinogens [65].…”

Section: Discussionmentioning

confidence: 99%

Assessment of hormonal activities and genotoxicity of industrial effluents using in vitro bioassays combined with chemical analysis

Fang

Ying

Zhao

et al. 2012

Enviro Toxic and Chemistry

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Wastewaters from various industries are a main source of the contaminants in aquatic environments. The authors evaluated the hormonal activities (estrogenic/anti‐estrogenic activities, androgenic/anti‐androgenic activities) and genotoxicity of various effluents from textile and dyeing plants, electronic and electroplate factories, pulp and paper mills, fine chemical factories, and municipal wastewater treatment plants in the Pearl River Delta region by using in vitro bioassays (yeast estrogen screen [YES]; yeast androgen screen [YAS]; and genotoxicity assay [umu/SOS]) combined with chemical analysis. The results demonstrated the presence of estrogenic, anti‐estrogenic, and anti‐androgenic activity in most industrial effluents, whereas no androgenic activities were detected in all of the effluents. The measured estrogenic activities expressed as estradiol equivalent concentrations (EEQs) ranged from below detection (3 of 26 samples) to 40.7 ng/L, with a mean of 7.33 ng/L in all effluents. A good linear relationship was found between the EEQs measured by YES bioassay and the EEQs calculated from chemical concentrations. These detected estrogenic compounds, such as 4‐nonylphenol and estrone, were responsible for the estrogenic activities in the effluents. The genotoxic effects expressed as benzo[a]pyrene equivalent concentrations (BaP EQs) varied between below detection and 88.2 µg/L, with a mean of 8.76 µg/L in all effluents. The target polycyclic aromatic hydrocarbons were minor contributors to the genotoxicity in the effluents, and some nontarget compounds in the effluents were responsible for the measured genotoxicity. In terms of estrogenic activities and genotoxicity, discharge of these effluents could pose high risks to aquatic organisms in the receiving environments. Environ. Toxicol. Chem. 2012;31:1273–1282. © 2012 SETAC

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Phthalates demonstrate genotoxicity on human mucosa of the upper aerodigestive tract

Cited by 69 publications

References 16 publications

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

Ovarian development in Wistar rat treated prenatally with single dose diisobutyl phthalate

Assessment of hormonal activities and genotoxicity of industrial effluents using in vitro bioassays combined with chemical analysis

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