Implications of the lack of accuracy of the lifetime rodent bioassay for predicting human carcinogenicity.

نویسندگان

  • Fanny K Ennever
  • Lester B Lave
چکیده

The NTP lifetime rodent bioassay (LRB) is the "gold standard" for predicting human carcinogenicity. Unfortunately, little attempt has been made to validate it against human carcinogenicity. Here we show that the extremely limited data available do not support either of the two common interpretations of LRB results. If a risk-avoidance interpretation is used where any positive result in a sex/species combination is considered positive, 9 of the 10 known human carcinogens tested are positive, but an implausible 22% of all chemicals are positive. If a less risk averse interpretation is used where only chemicals positive in both rats and mice are considered positive, only 3 of the 6 known human carcinogens tested are positive. In either interpretation, some known human carcinogens are not positive in the LRB, potentially allowing widespread human exposure to misidentified chemicals. Improving the predictive accuracy of the LRB and other tests for human carcinogenicity requires that test results be validated against the known human carcinogenicity of chemicals. This will require redirecting available resources from screening chemicals to validating carcinogenicity tests as well as a substantial investment in epidemiology to identify more known human carcinogens and presumed human non-carcinogens.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

RIVM report 340700001/2004 Transgenic mice as alternatives in carcinogenicity testing: current status

The correct prediction of human risk after exposure to chemical and physical compounds has long been a major challenge. For this, the lifetime bioassay using rats and mice is routinely used. However, over the years this assay has clearly come to reveal several drawbacks; for example, large numbers of animals are used, and the assays are slow, insensitive and expensive. On top of this, there is ...

متن کامل

Use of the Syrian hamster embryo cell transformation assay for carcinogenicity prediction of chemicals currently being tested by the National Toxicology Program in rodent bioassays.

The Syrian hamster embryo (SHE) cell transformation assay was used to predict the carcinogenicity of 26 chemicals currently being tested in the rodent bioassay by the National Toxicology Program as part of its program titled "Strategies for Predicting Chemical Carcinogenesis in Rodents." Of these 26 chemicals, 17 were found to be positive in the SHE cell transformation assay while 9 were negati...

متن کامل

Predicting the carcinogenicity of chemicals in humans from rodent bioassay data.

Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. We argue that it is always more useful to know a chemical's carcinogenic potency (with confidence limits) than to be able to say only qualitatively that it has been found to be a carcinogen. In a typical bioassay, a chemical is administered...

متن کامل

Prediction of rodent carcinogenesis: an evaluation of prechronic liver lesions as forecasters of liver tumors in NTP carcinogenicity studies.

The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in atte...

متن کامل

Predicting carcinogenicity in humans: The need to supplement animal-based toxicology

Traditional chemical carcinogenesis testing employs a 2-year rodent bioassay with nearly 900 animals for each chemical evaluation. In the interest of reducing, refining and replacing animals in testing, there is an immediate need for alternative methods of testing for carcinogenic compounds. Data analysis indicates human carcinogens may be detected as high as 90% but as low as 50% of the time w...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Regulatory toxicology and pharmacology : RTP

دوره 38 1  شماره 

صفحات  -

تاریخ انتشار 2003