US EPA

1239588 

Journal Article 

Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats 

Lington, AW; Bird, MG; Plutnick, RT; Stubblefield, WA; Scala, RA 

1997 

Yes 

Fundamental and Applied Toxicology
ISSN: 0272-0590
EISSN: 1095-6832 

ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS 

SAN DIEGO 

36 

1 

79-89 

English 

9073470 

10.1093/toxsci/36.1.79 

WOS:A1997WP30200009 

http://www.sciencedirect.com/science/article/pii/S0272059097922867
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has other version or edition 1065989 Chronic toxicity/oncogenicity study in F-344 rats (final report) with cover letter dated 042386
is related to other part(s) 1325509 Chronic feeding study in Fisher 344 rats (final pathology report) with cover letter dated 042386

Groups of 110 Fischer 344 rats/sex were fed diisononyl phthalate (DINP) at dietary levels of 0, 0.03, 0.3, and 0.6 wt% for periods up to 2 years. Interim sacrifices of 10 predesignated rats/sex/dose were at 6, 12, and 18 months with surviving animals sacrificed at 24 months. At study termination, survival was in excess of 60% for every group. At the mid or high dose, the following biological effects were noted: slight decreases in food consumption and body weight; slight increase in mortality; a dose-related increase in relative organ weights of liver and kidney; and some slight effects on urinalysis, hematologic, and clinical chemistry parameters. No peroxisome induction was observed in livers of treated rats compared with controls. No clear treatment-related nonneoplastic or neoplastic lesions were found. However, mononuclear cell leukemia (MNCL) and changes known to be associated with an increased incidence of MNCL were seen in the mid-dose and high-dose groups. A literature review suggests that MNCL is a common finding in aging F344 rats and that this increased incidence in rats treated with DINP is not relevant to man. A clear no-observed-effect level was demonstrated for all biological end points at a dietary level of 0. 03 wt% or approximately 17 mg/kg/day of DINP. 

Phthalic Acids; diisononyl phthalate; 4010KIX4CK; Index Medicus; Testis -- drug effects; Body Weight -- drug effects; Blood Chemical Analysis; Administration, Oral; Rats, Inbred F344; Spleen -- drug effects; Survival Rate; Hematologic Tests; Precancerous Conditions -- pathology; Carcinogenicity Tests; Adrenal Glands -- drug effects; Microbodies -- drug effects; No-Observed-Adverse-Effect Level; Animals; Urine -- chemistry; Leukemia, Experimental -- pathology; Leukemia, Experimental -- chemically induced; Organ Size -- drug effects; Spleen -- pathology; Adrenal Glands -- pathology; Liver -- drug effects; Kidney -- pathology; Kidney -- drug effects; Phthalic Acids -- toxicity; Liver -- pathology