Effect of orally administered plasticizers and polyvinyl chloride stabilizers in the rat

Nikonorow, M; Mazur, H; Piekacz, H

doi:10.1016/0041-008x(73)90259-7

Cited by 99 publications

(29 citation statements)

References 3 publications

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“…Decreased fetal weight is considered an early indicator of developmental toxicity (32) and has been observed in Wistar rats treated with 600 mg DBP/kg by gavage on gestation days 0-21 (33). Similar results were observed by Reel and Lawton (34) in an earlier DBP RACB study using Swiss mice.…”

Section: Discussionsupporting

confidence: 77%

Reproductive Toxicity of Di-n-Butylphthalate in a Continuous Breeding Protocol in Sprague-Dawley Rats

Wine¹,

Li²,

Barnes³

et al. 1997

Environmental Health Perspectives

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The esters of o-phthalic acid are employed extensively in the manufacture of plastics where they are used to impart flexibility. Since they are not covalently linked to the plastic polymer, they can leach from the matrix, providing opportunity for widespread exposure [see Thomas and Thomas (1) for review]. The phthalate ester di-nbutylphthalate (DBP) is used in the manufacture of consumer products as diverse as nail polish, insect repellents, and denture base material (2-4). DBP has recently been found to have clinical applications as well, selectively eliminating tumor cells from bone marrow (5,6).DBP has been previously characterized as a developmental and reproductive toxicant in the rat (7)(8)(9)(10)(11)(12). Comparable oral doses of DBP given to juvenile and adult male rats produces a testicular lesion characterized by early sloughing of germ cells, vacuolization of the Sertoli cell cytoplasm, and testicular atrophy (7,10). It has also been shown that the testicular toxicity of phthalates is age dependent, with immature animals being more sensitive than mature animals (13,14). However, the reproductive toxicity following exposure during development has not been addressed. Although no data are available specifically on the transfer of DBP across the placenta, studies with other phthalate esters show that these compounds readily cross the placenta of rats (15)(16)(17) (195) under the RACB protocol. This is expected in the RACB design because the Fo rats are exposed only as adults, the F1 rats are born to mothers that are treated during gestation and lactation, and the F1 animals themselves are treated during maturation to sexual maturity and through mating. The results of this DBP RACB study are presented below; the results show that structural defects are seen in the second generation rats that were not found in the first. MethodsGeneral. This study was conducted using the National Toxicology Program's RACB protocol for which the detailed methods have been previously described (20,21). Briefly, the protocol is composed of four segments, or tasks. Task 1 is a 14-day range-finding study that is used to set three dose levels used in Task 2. Task 2 is the 14-week continuous breeding phase, generating up to five litters per pair. Task 3 consists of crossover matings between treated and control Fo animals to determine the affected sex, and Task 4 assesses the fertility of the last litter (F1) born during continuous breeding (Task 2).Chemical. DBP was obtained from Chem Central via Midwest Research Institute (Kansas City, MO, Lot/Batch # L-121 1-83/02). The purity of DBP used in preparation of the feed formulations was greater than 99% as determined by gas chromatography. Dosed feed formulations. DBP was blended into powdered NIH-07 (Zeigler Bros., Gardeners, PA) feed on a weight-to-

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Section: Discussionsupporting

confidence: 77%

Reproductive Toxicity of Di-n-Butylphthalate in a Continuous Breeding Protocol in Sprague-Dawley Rats

Wine¹,

Li²,

Barnes³

et al. 1997

Environmental Health Perspectives

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“…The deleterious effects of di(2-ethylhexyl) phthalate (DEHP) on developing embryos and/or fetuses in animals have been reported by a number of investigators (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Teratogenicity/fetotoxicity of DEHP in mice.

Tomita¹,

Nakamura²,

Yagi³

et al. 1982

Environ Health Perspect

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The embryonic/fetotoxic effects of DEHP on pregnant mice (ddY-Slc Y x CBA Cd) were studied. DEHP was administered orally in dosages of 0.05 ml/kg to 30.0 mg/kg on day 6, 7, 8, 9 or 10 of gestation. A single administration of DEHP over 0.1 ml/kg (1/300 of LD50) on day 7 of gestation decreased the numbers and the body weight of living fetuses, whereas no significant changes in the numbers of living fetuses (with no gross and skeletal abnormalities) were observed compared with those of the control group, when 0.05 ml/kg (1/600 of LD50) of DEHP was administered. The fetotoxicity (fetal death) was dose dependent. The LD50 and the nonfetolethal maximum dosage of DEHP in its single, oral administration was 592 mg/kg and 64 mg/kg, respectively. The latter value is much higher than an estimated DEHP intake from commercial foodstuffs in men, which is approximately 0.03 mg/kg/day.

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“…Nikonorow et al (16) reported that the oral administration of DEHP caused a significant reduction in placental weights. This finding led the authors to conclude that the effects of orally administered DEHP on reproduction and fetal development were dose-dependent and were influenced by the duration of phthalate administration.…”

Section: Teratologymentioning

confidence: 99%

Effects of Phthalic Acid Esters (PAEs) on the Neonate and Aspects of Teratogenic Actions

Thomas¹,

Wienckowski²,

Gillies³

et al. 1986

Environmental Health Perspectives

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A review of the literature reveals that several different phthalic acid esters (PAEs) are capable of causing testicular damage. Phthalate-induced zinc deficiency is consistent with germinal epithelial damage. Among experimental animals, mice perhaps show the greatest sensitivity to phthalate-induced terata, but high doses/exposure are required. Little toxicologic information is available with regard to phthalate-induced effects upon the neonate.

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Effect of orally administered plasticizers and polyvinyl chloride stabilizers in the rat

Cited by 99 publications

References 3 publications

Reproductive Toxicity of Di-n-Butylphthalate in a Continuous Breeding Protocol in Sprague-Dawley Rats

Reproductive Toxicity of Di-n-Butylphthalate in a Continuous Breeding Protocol in Sprague-Dawley Rats

Teratogenicity/fetotoxicity of DEHP in mice.

Effects of Phthalic Acid Esters (PAEs) on the Neonate and Aspects of Teratogenic Actions

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