EPA Science Inventory

Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

Citation:

Tokar, E., B. Diwan, D. Thomas, AND M. Waalkes. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice. Archives of Toxicology 86(6):975-82, (2012).

Description:

Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the biological methylation of inorganic arsenic, could be a key carcinogenic species. Thus, pregnant CD1 mice were provided drinking water containing MMA3+ at 0 (control), 12.5 or 25 parts per million (ppm) from gestational day 8 to 18. Tumors were assessed in groups of male or female (initial n = 25) offspring up to two years of age. In utero treatment had no effect on survival or body weights. Female offspring exhibited increases in total epithelial uterine tumors (control 0%; 12.5 ppm 26%; 25 ppm 30%), oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%), adrenal cortical adenoma at 25 ppm (control 0%; 12.5 ppm 9%; 25 ppm 26%), and total epithelial ovarian tumors (control 0%; 12.5 ppm 39%; 25 ppm 26%). Male offspring showed dose-related increases in hepatocellular carcinoma (control 0%; 12.5 ppm 12%; 25 ppm 22%), adrenal adenoma (control 0%; 12.5 ppm 28%; 25 ppm 17%), and lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring had unusual testicular lesions, including two rete testis carcinomas and two adenomas, and three interstitial cell tumors. Overall, maternal consumption of MMA3+ during pregnancy in CD1 mice produced some similar proliferative lesions as gestationally applied inorganic arsenic in the offspring during adulthood.

Purpose/Objective:

This ms describes occurrence of proliferative lesions and tumors in CD1 mice exposed transplacentally to methylarsonous acid (MAsIII). Here, pregnant mice had free access to drinking containing up to 25 ppm MAsIII between gestational days 8 to 18. Up to two years of age, female mice exhibited reproductive tract tumors and male mice exhibited lung, adrenal, and liver tumors as well as lesions in testes.

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 06/01/2012
Completion Date: 06/01/2012
Record Last Revised: 10/29/2012
Record Created: 07/10/2012
Record Released: 07/10/2012
OMB Category: Other
Record ID: 244933

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

INTEGRATED SYSTEMS TOXICOLOGY DIVISION

PHARMACOKINETICS BRANCH