Reproductive toxicity phthalates

The reproductive toxicity of some phthalate esters has been reviewed by the Commission of the European Communities (45). This review concludes that testicular atrophy is the most sensitive indicator of reproductive impairment and that the rat is the most sensitive species. 

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. 

Martino-Andrade AJ, Chahoud I (2010) Reproductive toxicity of phthalate esters. Mol Nutr Food Res 54 148-157... 

Tyl RW, Myers CB, Marr MC (2004) Reproductive toxicity evaluation of butyl benzyl phthalate in rats. Reproduc Toxicol 18 241-264... 

In another study, CD-I mice were exposed via the diet to 0. 0.01, 0.025 or 0.05% di(2-ethylhexyl) phthalate in the diet on days 0-17 of gestation, and the offspring were evaluated for acquisition of developmental landmarks, spontaneous locomotor activity and fertility. The summary report of the study indicates that no effects were observed on reproductive toxicity in either generation (National Toxicology Program, 1997b). 

Aquatic aqueous enteric coating (cellulose acetate phthalate, distilled acetylated monoglycerides, and poloxamer 188) Film coating for tablets and capsules Repeat-dose toxicity with routine end points (90 days—diet rat), reproduction toxicity (embryo-fetal study in rat) and genotoxicity (2 in vitro and 1 in vivo studies) No adverse toxicity, reprotoxicity, or genotoxicity 31, 32... 

Kavlock R, Bockelheide K, Chapin R, et al. (2002) NTP center for the evaluation of risks to human reproduction Phthalates expert panel report on the reproductive and developmental toxicity of di- -octyl phthalate. Reproductive Toxicology 16(5) 721-734. 

Phthalates are primarily used as plasticizers, to increase the pliability of plastics such as PVC. Most concern centres on the leaching of phthalates from plastics into drinking water and food. About 2.7 Mtyr-1 are produced globally, of which some 50% comprises di(2-ethylhexyl)phthalate (or DEHP Fig. 7.13). Total losses to the environment are estimated at c. 7.7 ktyr-1. DEHP is a reproductive toxicant and a carcinogen in animals. 

Lovekamp-Swan, T., and B. J. Davis. 2003. Mechanisms of phthalate ester toxicity in the female reproductive system. Environmental Health Perspectives 111 139-145. 

Species and sex differences in the reproductive toxicity of di- -butyl phthalate are evident. While severe seminiferous tubular atrophy was observed in rats and guinea pigs at 2,000 mg/kg/day for 7-9 days, only focal atrophy was reported in mice at the same dose, and no effects on the testes were seen in Syrian hamsters (Gray et al. 1982). Testicular atrophy was observed in rats following intermediate-duration exposure to 720 mg/kg/day (NTP 1995) this effect was not observed in mice exposed to 3,689 mg/kg/day (NTP 1995). The species differences may be related to the greater ability of some species to conjugate the primary metabolite of di- -butyl phthalate (see Section 3.3.3.2). 

Reproductive Toxicity. No data on the reproductive toxicity of di- -butyl phthalate in humans were... 

Wine R, Li L, Barnes L, et al. 1997. Reproductive toxicity of di-n-butyl phthalate in a continuous breeding protocol in Sprague-Dawley rats. Environ Health Perspect 105 102-107. 

The acute oral toxicity is very low. Ingestion may result in nausea, somnolence, hallucination, and lacrimation. In humans, such effects may be noted at a dose level of 150-200 mg/kg. The recovery is prompt. The oral LD50 value in mice is in the range 6500 mg/kg. Its irritant action on the skin and the eyes of rabbits was mild. Di-n-octyl phthalate fed to mice at the 5% level in diet showed no reproductive toxicity. 

With regard to phthalates, DEHP has been shown to irrduce rrraterrral liver MT arrd lead to a functiorral zinc deficiency in the embryo indicating that altered Zn metabolism may contribute to DEHP-irrduced reproductive toxicity and teratogerricity. Irrtubation of... 

The reproductive toxicity of some phthalate esters has recently been reviewed by the Commission of the European Communities [8]. This review concludes that testicular atrophy is the most sensitive indicator of reproductive impairment and that the rat is the most sensitive species. The no effect level for body, testes, epidid3miis and prostate weights and for endocrine and gonadal effects of DEHP in male animals after oral administration was considered to be 69mg/kg body weight per day. This conclusion was endorsed by the Danish Institute of Toxicology [9]. 

In Europe, after publication of several extensive analyses and risk assessments for a number phthalate esters, several phthalates with the C4-C6 backbones were listed with a Category 2 or Category 3 CMR (Carcinogenic, Mutagenic, or Reproductively-toxic)... 

Benzoate based plasticizers, e.g., Benzoflex 2888 which is a blend of diethylene glycol dibenzoate, triethylene glycol dibenzoate, and dipropylene glycol dibenzoate, have been developed to account for the leaching problems. Benzoflex seems to be a good alternative to phthalates in flexible toys due to its ease of processing, final product performance, low toxicity and fast biodegradation. Toxicity tests showed a low acute toxicity and no evidence of reproductive toxicity (2). 

Keywords Phthalates Testosterone Male reproduction Female reproduction Reproductive toxicity Sperm count Plastics Vinyl Polyvinyl chloride PVC Food Food packaging Food contact material Consumer products Children s toys Medical equipment Neonatal intensive care unit Intravenous bags DEP DBP DnBP DiBP BBzP DEHP DINP... 

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