Division 5.3 Short-term toxicity

Short-term toxicity studies shall be designed to provide information as to the amount of the active substance that can be tolerated without adverse effects under the conditions of the study and to elucidate health hazards occurring at higher dose levels. Such studies provide useful data on the risks for those handling and using plant protection products containing the active substance, among other possible exposed groups. In particular, short-term studies provide an essential insight into possible repeated actions of the active substance and the risks to humans who may be exposed. In addition short-term studies provide information useful in the design of chronic toxicity studies.

The studies, data and information to be provided and evaluated, shall be sufficient to permit the identification of effects following repeated exposure to the active substance, and in particular to further establish, or indicate:

1. (a)

   the relationship between dose and adverse effects;

2. (b)

   toxicity of the active substance including where possible the No Observed Adverse Effect Level (NOAEL);

3. (c)

   target organs, where relevant (including immune, nervous and endocrine systems);

4. (d)

   the time course and characteristics of adverse effects with full details of behavioural changes and possible pathological findings at post-mortem;

5. (e)

   specific adverse effects and pathological changes produced;

6. (f)

   where relevant the persistence and reversibility of certain adverse effects observed, following discontinuation of dosing;

7. (g)

   where possible, the mode of toxic action;

8. (h)

   the relative hazard associated with the different routes of exposure;

9. (i)

   relevant critical endpoints at appropriate time points for setting reference values, where necessary.

Toxicokinetic data (that is to say blood concentration) shall be included in short term studies. In order to avoid increased animal use, the data may be derived in range finding studies.

If nervous system, immune system or endocrine system are specific targets in short term studies at dose levels not producing marked toxicity, supplementary studies, including functional testing, shall be carried out (see point 5.8.2).