NTP technical report on the toxicology and carcinogenesis studies of di(2-ethylhexyl) phthalate (CASRN 117-81-7) administered in feed to sprague dawley (Hsd:Sprague Dawley(r) SD(r)) rats
The occurrence of pancreatic acinar adenoma or carcinoma (combined) in female rats was considered to be related to exposure. The BMD analysis shows there was no consistent pattern indicating that perinatal and postweaning exposure was more sensitive compared to postweaning-only exposure and modeled...
| Corporate Author: | |
|---|---|
| Format: | eBook |
| Language: | English |
| Published: |
Research Triangle Park, North Carolina, USA
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
December 2021, 2021
|
| Series: | Technical report
|
| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | The occurrence of pancreatic acinar adenoma or carcinoma (combined) in female rats was considered to be related to exposure. The BMD analysis shows there was no consistent pattern indicating that perinatal and postweaning exposure was more sensitive compared to postweaning-only exposure and modeled responses were within threefold of each other. However, there was a stronger carcinogenic response in the reproductive organs (uterus and testis) in the postweaning-only exposure study compared to the perinatal and postweaning exposure study. Perinatal and postweaning exposure to DEHP (Study\s1) resulted in increased incidence of nonneoplastic lesions in the liver, kidney, heart (male), pancreas (female), pituitary gland (male), bone marrow (male), testis, and epididymis. In addition, exposure increased gross lesions within the reproductive tract of males and females. Postweaning exposure to DEHP (Study\s2) resulted in increased incidence of nonneoplastic lesions in the liver, pancreas, heart (male), pituitary gland (male), bone marrow (male), testis, epididymis, and uterus.SYNONYMS: Bis(2-ethylhexyl)phthalate; dioctyl phthalate; phthalic acid di(2-ethylhexyl) ester; bis(2-ethylhexyl) 1,2-benzenedicarboxylate; 1,2-benzenedicarboxylic acid bis(2-ethylhexyl) ester TRADE NAMES: Platinol DOP; Octoil; Silicol 150; Bisoflex 81; Eviplast 80 Significant increases in the incidences of hepatocellular adenoma, hepatocellular adenoma or carcinoma (combined), pancreatic acinar adenoma, and pancreatic acinar adenoma or carcinoma (combined) were observed in the 3,000 and 10,000\sppm male rats relative to the control group. Higher incidences of hepatocellular carcinomas (10,000\sppm males) and pancreatic acinar carcinomas (3,000\sppm males) were also observed. In female rats, significant increases in the incidences of liver neoplasms occurred in the 3,000\sppm (hepatocellular adenoma and hepatocellular adenoma or carcinoma [combined]) and 10,000\sppm (hepatocellular carcinoma and hepatocellular adenoma or carcinoma [combined]) groups. Occurrences of pancreatic acinar adenomas were observed in the 3,000 and 10,000\sppm female groups, and a trend of higher incidence of uterine adenocarcinomas with increasing exposure was observed given the incidence in the 10,000\sppm group. The occurrence of uterine (including cervix) adenoma, adenocarcinoma, squamous cell carcinoma, or squamous cell papilloma (combined) in female rats may have been related to exposure. Under the conditions of the postweaning-only feed study (Study\s2), there was clear evidence of carcinogenic activity of DEHP in male Hsd:Sprague Dawley(r) SD(r) rats based on the increased incidences of hepatocellular adenoma or carcinoma (combined) and acinar adenoma or carcinoma (combined) neoplasms (predominately adenomas) of the pancreas. The occurrence of testicular interstitial cell adenoma in male rats may have been related to exposure. There was clear evidence of carcinogenic activity of DEHP in female Hsd:Sprague Dawley(r) SD(r) rats based on the increased incidences of hepatocellular adenoma or carcinoma (combined) and uterine (including cervix) adenoma, adenocarcinoma, squamous cell carcinoma, or squamous cell papilloma (combined). Nonneoplastic lesions were observed in the liver (male and female), pancreas (female), testis, epididymis, kidney (male and female), heart (male only), bone marrow (male only), and pituitary gland (male only). CONCLUSIONS: Under the conditions of the perinatal and postweaning feed study (Study\s1), there was clear evidence of carcinogenic activity of di(2-ethylhexyl) phthalate (DEHP) in male Hsd:Sprague Dawley(r) SD(r) rats based on the increased incidences of hepatocellular adenoma or carcinoma (combined) and acinar adenoma or carcinoma (combined) neoplasms (predominately adenomas) of the pancreas. There was clear evidence of carcinogenic activity of DEHP in female Hsd:Sprague Dawley(r) SD(r) rats based on the increased incidence of hepatocellular adenoma or carcinoma (combined). The occurrence of pancreatic acinar adenoma or carcinoma (combined) was considered to be related to exposure. PERINATAL AND POSTWEANING STUDY IN RATS (STUDY\S1): During the perinatal period, lower maternal mean body weight, maternal mean body weight gain, and feed consumption were observed in F0\sdams exposed to 10,000 ppm DEHP relative to control animals. Also in that exposure group, litter size and pup weights on PND\s1 were significantly decreased compared to the control group. Male and female pup mean body weight gains were significantly decreased in the 10,000\sppm group during lactation and resulted in significantly decreased pup body weights at weaning when compared to the control group. Pup survival was not affected following gestational and lactational DEHP exposure. Following perinatal and 2\syears of postweaning DEHP exposure, survival of exposed male and female rats to study termination was similar to that of control groups; however, there were decreases in mean body weight in the 10,000\sppm group compared to the control group. |
|---|---|
| Physical Description: | 1 PDF file (various pagings) illustrations |