書誌事項
- タイトル別名
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- Toxicity Evaluation of DINP and Estimation of The Tolerable Daily Intake
- DINP ノ ドクセイ ヒョウカ ト タイヨウ1ニチ セッシュリョウ ノ サンテイ
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<p>As di-isononyl phthalate (DINP), like di(2-ethylhexyl) phthalate (DEHP), has been used as a plasticizer for children's toys, people are worried about children's health because of possible exposure through chewing. Therefore in this article, we have collected and evaluated all toxicological information on DINP and estimated the tolerable daily intake (TDI). This toxicity assessment covers the unpublished but evaluated information in the report by the Center for the Evaluation of Risks to Human Reproduction (CERHR) (US NTP program), as published available data are limited. DINP is an ester of phthalic acid with two isononyl alcohols but these latter highly variable, including branched nonyl forms such as dimethyl heptanols and methylethyl hexanols. 1. Disposition and metabolism DINP was not easily absorbed through the skin but significant amounts were absorbed via the gastrointestinal tract after hydrolysis to the monoester, mono-isononyl phthalate (MINP). The major excretory forms of DINP in the urine were phthalic acid and the metabolites of MINP with oxidized branched chains. 2. General toxicity and carcinogenicity Two rat and one mouse carcinogenicity study have been conducted. Hepatic tumors with peroxisome proliferation were observed in both rats and mice, but these occur at high incidences in rodents since they have much higher expression of the peroxisome proliferator-activated receptor α (PPAR α) in their livers than other animals including dogs, monkeys and humans. Mononuclear cell leukemia occurred in F344 rats but this change is generally accepted to be specific to this rat strain. Renal changes and tumors found in only male rats were also specific phenomena as there is evidence of α2U-globulin involvement and this protein is only produced in male rats. Therefore, the above three specific toxicity endpoints were considered not relevant to humans. The lack of adverse effect of DINP in marmoset and cynomolgus monkey studies supports this judgment. However, some hepatotoxic effects including hepatocellular enlargement and focal necrosis without peroxisome proliferation appeared in one rat study. Based on the hepatic changes, the no observed adverse effect level (NOAEL) for repeated dose toxicity was concluded to be 15 mg/kg bw/day. 3. Genotoxicity Studies such as the Ames test, mouse lymphoma test, chromosome aberration test in vitro and micronucleus test in vivo have all indicated no genotoxic potential. CERHR also concluded that DINP is not genotoxic. 4. Reproductive toxicity No adverse effects on any reproductive parameters, including mating, fertility and delivery indexes, were observed in either one- or two-generation rat studies. 5. Developmental toxicity A significant increase in the incidence of skeletal variations and dilation of the renal pelvis was found in rat fetuses in the teratogenicity study. Furthermore, a low viability and low body weights of offspring before weaning were observed in the rat generation study. From these studies, the NOAEL for developmental toxicity and the lowest observed effect level were estimated to be 100 mg/kg bw/day and 143 - 285 mg/kg bw/day, respectively. 6. Other toxicity DINP may not have estrogenic activity because of negative results in receptor binding, yeast, MCF-7 and uterotrophic assays. No testicular toxicity of DINP, even at high doses, was observed in three rodent and two monkey studies although DEHP induces severe toxicity in testes of rodents at low doses. Relative high dosing of DINP from gestation day 14 to lactation day 3 induced slight abnormalities of male reproductive organs of the offspring, suggesting that DINP shows weak antiandrogenic activity. 7. Establishment of a TDI An appropriate NOAEL to derive a TDI for DINP was 15 mg/kg bw/day from the 2 year carcinogenicity rat study and 100 mg/kg bw/day from the rat teratogenicity study. As both studies were performed under acceptable </p><p>(View PDF for the rest of the abstract.)</p>
収録刊行物
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- 日本食品化学学会誌
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日本食品化学学会誌 9 (2), 39-45, 2002
日本食品化学学会
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詳細情報 詳細情報について
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- CRID
- 1390282680171933824
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- NII論文ID
- 110007367245
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- NII書誌ID
- AA11666400
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- ISSN
- 21896445
- 13412094
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- NDL書誌ID
- 6339245
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可