مجموعة أدوات تسجيل مبيدات الآفات

#617 Long-term oral toxicity

Objective of the study

The objective of a long-term, or chronic, oral toxicity study is to determine the effects of a substance in a mammalian species following prolonged and repeated exposure. More specifically, the long-term oral study aims to:
  • Identify the chronic toxicity of a chemical;
  • Identify target organs;
  • Characterise the dose-response relationship;
  • Identify a no-observed-adverse-effect level (NOAEL), or point of departure for establishment of a Benchmark Dose (BMD)
If possible, the long-term oral toxicity study should be combined with the carcinogenicity study
 

Circumstances under which the study is recommended to be required

The long-term oral toxicity study is recommended if either if:
  1. The use of the pesticide is likely to result in repeated human exposure over a considerable portion of the human lifespan; or
  2. The use requires a maximum residue limit or an exemption from the requirement of a maximum residue limit.
If it is claimed that such testing is unnecessary, that claim shall be fully justified.
 

Test organism

The long-term oral toxicity study is normally conducted with rats.
Studies designed to simultaneously fulfil the requirements of both the chronic oral and carcinogenicity 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.

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.
 

Test guidelines

The following test guidelines may be used for the long-term oral toxicity study:
•OECD Guidelines for the Testing of Chemicals. Test No. 452: Chronic toxicity studies.
•OECD Guidelines for the Testing of Chemicals. Test No. 453: Combined chronic toxicity/carcinogenicity studies.
•US EPA Health Effects Test Guidelines. OPPTS 870.4100. Chronic toxicity.
•US EPA Health Effects Test Guidelines. OPPTS 870.4300. Combined chronic toxicity/carcinogenicity.
•EC Testing Method B.30. Chronic toxicity test. Council Regulation (EC) No 440/2008.
•EC Testing Method B.33. Combined chronic toxicity/carcinogenicity test. Council Regulation (EC) No 440/2008.