NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-hexyl 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)00030-8

Cited by 47 publications

(27 citation statements)

References 21 publications

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“…These fi ndings are consistent with a limited peroxisome proliferation and are in agreement with previous short term toxicity studies with DnHP or DCHP. Thus, young male Wistar rats given 20 000 ppm DnHP in diet (estimated 1824 mg kg −1 per day, Kavlock et al, 2002), for 10 or 21 days, showed slight increase in liver weight and minimal induction of one peroxisomal enzyme (i.e. cyanide-insensitive palmitoyl CoA oxidase; Mann et al, 1985).…”

Section: Discussionmentioning

confidence: 97%

“…DnHP is rarely produced for directly commercial uses (Kavlock et al, 2002). More often, it is a component of various phthalate mixtures and care should be taken to its level when estimating their potential health impact.…”

Section: Discussionmentioning

confidence: 99%

“…DnHP is often found as a component of commercial C6-C10-phthalate mixtures or diisohexyl phthalates at levels up to 25% (Kavlock et al, 2002). Phthalates are not covalently bound to polymers and can leach out in the environment (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Differential developmental toxicities of di‐n‐hexyl phthalate and dicyclohexyl phthalate administered orally to rats

Saillenfait

Gallissot²,

Sabaté³

2009

J of Applied Toxicology

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The objective of this study was to evaluate the developmental toxic potential of di-n-hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague-Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg -1 per day, by gavage, on gestational days (GD) 6-20. Maternal food consumption and body weight gain were signifi cantly reduced at 750 mg kg -1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused doserelated developmental toxic eff ects, including marked embryo mortality at 750 mg kg -1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and signifi cant decreases in fetal weight at 500 and 750 mg kg -1 per day. Signifi cant delay of ossifi cation and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg -1 per day. DCHP produced fetal growth retardation at 750 mg kg -1 per day, as evidenced by signifi cant reduction of fetal weight. DnHP and DCHP induced a signifi cant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a signifi cant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg -1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Differential developmental toxicities of di‐n‐hexyl phthalate and dicyclohexyl phthalate administered orally to rats

Saillenfait

Gallissot²,

Sabaté³

2009

J of Applied Toxicology

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“…Os ftalatos, incluindo o DHP, têm sido considerados poluentes ambientais, e mesmo sendo controlados em vários países, os seres humanos estão expostos a eles diretamente através de ingestão, inalação e exposição cutânea. 65 Kim et al 45 estudaram a eficácia da cutinase de Fusarium oxysporum e esterase de Candida cylindracea na degradação do DHP. A cutinase atua de forma muito mais rápida e precoce que a esterase, com alta atividade hidrolítica.…”

Section: Química De Polímerosunclassified

Cutinases fúngicas: propriedades e aplicações industriais

et al. 2008

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Recebido em 18/12/07; aceito em 20/6/08; publicado na web em 10/11/08 FUNGAL CUTINASES: PROPERTIES AND INDUSTRIAL APPLICATIONS -REVIEW.Cutinases (EC 3.1.1.74) are also known as cutin hidrolases. These enzymes share catalytic properties of lipases and esterases, presenting a unique feature of being active regardless the presence of an oil-water interface, making them interesting as biocatalysts in several industrial processes involving hydrolysis, esterification and trans-esterification reactions. They are also active in different reaction media, allowing their applications in different areas such as food industry, cosmetics, fine chemicals, pesticide and insecticide degradation, treatment and laundry of fiber textiles and polymer chemistry. The present review describes the characteristics, potential applications and new perspectives for these enzymes.Keywords: cutinase; industrial applications; biochemical characteristics. introduçÃoCutinases são enzimas que catalisam a hidrólise de um biopoliéster insolúvel, a cutina, componente estrutural da cutícula das plantas.1 Este poliéster é composto do seguintes ácidos graxos: ω-hidróxi ácidos graxos, ácido diidroxidróxi palmítico, e ácidos 18-hidróxi-9,10,-epóxi C 18 saturados e Δ12 insaturados, e ácidos 9,10,18-triidróxi C 18 saturados e Δ12 monoinsaturados. A composição da cutina é dependente da espécie, porém, em geral, em plantas de crescimento rápido predominam os ácidos de 16 carbonos, particularmente diidroxipalmitato, enquanto em plantas de crescimento lento uma mistura de ácidos de 16 e 18 carbonos é encontrada. A cutinase libera hidroliticamente todos os tipos de monômeros a partir do polímero. 2Além da hidrólise, assim como as lipases, as cutinases também são capazes de catalisar reações reversas, como esterificação, transesterificação (interesterificação, alcoólise e acidólise) e aminólise, sendo que a atividade de água do meio reacional é um dos fatores determinantes para cada classe de reação. 3,4 Segundo Brenda 5 a cutinase é classificada como EC 3.1.1.3 com nome recomendado de triacilglicerol lipase, e nome sistemático de triacilglicerolacil-hidrolase. Também é classificada, pela mesma fonte, como 3.1.l.74 com nome recomendado de cutinase e nome sistemático de cutina hidrolase, ou seja, uma esterase que hidrolisa a cutina, podendo agir e ser classificada também como lipase.As cutinases apresentam diversas características interessantes para aplicações em uma ampla gama de produtos, variando de detergentes a alimentos.6 Conseqüentemente, tem sido desenvolvida intensa pesquisa abordando suas estruturas, funções, purificação e aplicações, visando o desenvolvimento de novos processos empregando este grupo de enzimas. 1O presente artigo descreve as características e potenciais aplicações das cutinases fúngicas em processos industriais. Características das cutinasesCutinases são dos menores membros da família serina hidrolase, que apresenta a tríade catalítica clássica composta por serina, histidina e um grupo carboxil. A sub-família das cutinases consiste em ...

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“…Di-n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) belong to the family of phthalic acid di-esters, which are produced in large quantities, and are primarily used as softeners and plasticizers in commonly used plastics; they are found in a wide variety of media ranging from drinking water to infant formulae (4). DHP and DCHP were found in food and in indoor environments (5).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and Histopathological Effects of in Utero Di-N-Hexyl Phthalate and Di-Cyclohexyl Phthalate Exposure on the Thyroid Axes and T3, T4, TSH Hormone Levels of Male and Female Rats: at Adulthood

Göktekin¹,

Barlas²

2017

Erciyes Med J

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Objective: To investigate the effects of di-n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) on hypophysis/thyroid axis in utero, pregnant rats were exposed to DHP or DCHP at doses of 0, 20, 100, and 500 mg/kg bw/d, by gavage, on gestational days (GD) 6-19. Materials and Methods:The rats were allowed to grow up until adult (PD 90) stages. Body weights were recorded weekly. After treatment period, hormone analysis was determined in serum samples. Histopathological examinations revealed histopathological changes in thyroid gland on rats that received DHP or DCHP.Results: There were no significant differences in body weights of male adult rats among groups. However, in female rats, final body weights were statistically decreased in 100 mg/kg/d DHP group but increased in DCHP treated rats at dose of 100 and 500 mg/kg/d in dose-response experiment. There was a decrease of TSH level in DHP 100 mg/kg/d and DCHP 500 mg/kg/d groups in male and female rats. T4 levels were increased in DCHP 20 and 100 mg/kg/d groups. In male rats, an increase of TSH level was found in DCHP 20 and 100 mg/kg/d treatment groups. Similarly, an increase of T3 level was found in DCHP 100 and 500 mg/kg/d groups. Also, in thyroid tissue, increase of adipose tissue, colloidal degeneration, and follicular degeneration was observed in all treatment groups. Conclusions:The results of this study suggest that DHP and DCHP, which was applied in pregnancy period, cause changes to T3, T4, and TSH hormone levels and thyroid histology in adult rats.

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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-hexyl phthalate

Cited by 47 publications

References 21 publications

Differential developmental toxicities of di‐n‐hexyl phthalate and dicyclohexyl phthalate administered orally to rats

Differential developmental toxicities of di‐n‐hexyl phthalate and dicyclohexyl phthalate administered orally to rats

Cutinases fúngicas: propriedades e aplicações industriais

Biochemical and Histopathological Effects of in Utero Di-N-Hexyl Phthalate and Di-Cyclohexyl Phthalate Exposure on the Thyroid Axes and T3, T4, TSH Hormone Levels of Male and Female Rats: at Adulthood

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