Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats.
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.
Lington
A W
AW
Exxon Biomedical Sciences, Inc., East Millstone, New Jersey, 08875-2350, USA.
Bird
M G
MG
Plutnick
R T
RT
Stubblefield
W A
WA
Scala
R A
RA
D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D005260:Female; D006403:Hematologic Tests; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007942:Leukemia, Experimental / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008830:Microbodies / Q000187:drug effects; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010795:Phthalic Acids / Q000633:toxicity*; D011230:Precancerous Conditions / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D015996:Survival Rate; D013737:Testis / Q000187:drug effects; D014556:Urine / Q000737:chemistry
D010795:Phthalic Acids; C012125:diisononyl phthalate