Ovarian toxicity and carcinogenicity in eight recent National Toxicology Program studies

Area of Science:

• Toxicology
• Oncology
• Reproductive Science

Background:

• Ovarian toxicity and carcinogenicity are significant concerns.
• National Toxicology Program (NTP) studies evaluate chemical safety in rodents.

Purpose of the Study:

• To review chemicals causing ovarian toxicity and/or carcinogenicity in NTP studies.
• To identify common ovarian lesions and neoplasms associated with chemical exposure.
• To explore the relationship between non-neoplastic ovarian changes and neoplasia.

Main Methods:

• Analysis of data from National Toxicology Program (NTP) prechronic and chronic rodent studies.
• Identification of chemicals associated with treatment-related ovarian lesions.
• Classification of non-neoplastic ovarian changes and observed neoplasms.
• Examination of associations between ovarian lesions and subsequent neoplasia.

Main Results:

• Eight chemicals were identified: 1,3-butadiene, 4-vinylcyclohexene, vinylcyclohexene diepoxide, nitrofurantoin, nitrofurazone, benzene, delta-9-tetrahydrocannabinol, and tricresylphosphate.
• Common non-neoplastic ovarian changes included hypoplasia, atrophy, follicular necrosis, and tubular hyperplasia.
• Granulosa cell tumors and benign mixed tumors were the most frequent treatment-related neoplasms.
• Evidence suggests a link between antecedent ovarian hypoplasia, atrophy, and hyperplasia and subsequent ovarian neoplasia.
• Associated pathological changes were observed in adrenal glands and uterus.

Conclusions:

• Multiple chemicals can induce ovarian toxicity and carcinogenicity in rodents.
• Non-neoplastic ovarian changes may precede the development of ovarian neoplasms.
• Further research into chemical-induced ovarian toxicity is warranted.