Pesticide Registration Toolkit

#618 Carcinogenicity (two rodent species)

Objective of the study

The objective of carcinogenicity study is to determine the carcinogenic effects of a substance in a mammalian species following prolonged and repeated exposure. More specifically, the carcinogenicity study aims to:
  • Identify the carcinogenic properties of a chemical, resulting in an increased  incidence of neoplasms, increased proportion of malignant neoplasms or a reduction in the  time to appearance of neoplasms, compared with concurrent control groups;
  • Identify target organ(s) of carcinogenicity;
  • Identify the time to appearance of neoplasms; 
  • Characterise the tumour dose-response relationship; 
  • Identify of a no-observed-adverse-effect level (NOAEL) or point of departure for establishment of a Benchmark Dose (BMD).
If possible, the carcinogenicity study should be combined with the long-term oral toxicity study 
 

Circumstances under which the study is recommended to be required

The carcinogenicity study is recommended  if:
  1. The use of the pesticide is likely to result in significant human exposure over a considerable portion of the human lifespan which is significant in terms of either frequency, duration or magnitude of exposure; or
  2. The use requires a maximum residue limit or an exemption from the requirement of a maximum residue limit; or
  3. The active ingredient, metabolite, degradate, or impurity (a) is structurally related to a recognized carcinogen, or (b) causes mutagenic effects as demonstrated by in vitro or in vivo testing, or (c) produces a morphologic effect in any organ (e.g. hyperplasia, metaplasia) in sub-chronic studies that may lead to a neoplastic change.
If it is claimed that such testing is unnecessary, that claim shall be fully justified.
 

Test organism

The carcinogenicity study is normally conducted in two rodent species; rat and mouse are preferred.
Studies designed to simultaneously fulfil the requirements of both the carcinogenicity and the chronic oral studies (i.e. a combined study) may be conducted. Minimum acceptable study durations are: 
  1. Chronic rodent study (food use): 24 months. 
  2. Chronic rodent study (non-food use): 12 months. 
  3. Mouse carcinogenicity study: 18 months. 
  4. Rat carcinogenicity study: 24 months.
If comparative metabolism data indicate that either rat or mouse is an inappropriate model for human cancer risk assessment, an alternative species should be considered.
 

Test substance

  • Technical grade active ingredient
 

Typical endpoints of the study

The No Observed Adverse Effect Level (NOAEL) is reported whenever possible.
Other typical endpoints of the study include, but are not limited to: survival, body weight, toxic response, necropsy findings, histopathological findings.
Conventional histopathological terminology such as that published by the International Agency for Research on Cancer (IARC) should be used in the nomenclature and reporting of tumours.
 

Test guidelines

The following test guidelines may be used for the long-term oral toxicity study: