Table 1. Classification of Studies According to How Well They Address the Read-Across Hypothesis.

Level	Exposure concentration	Endpoints	Internal concentration	Specific Pharmacological Effects	Comments
4	Measured	Mode of action related	Measured	Seen only at HTPCa	Experimental design has integrated information from mammalian data
3	Measured	Mode of action related	X	Cannot be related to HTPC
2	Measured	X	X	X	Experimental design is independent from mammalian data
1	X	X	X	X

^aH_TPC, human therapeutic plasma concentration. Only studies at Level 4 address all aspects of the read-across hypothesis, and can relate effects to the human therapeutic plasma concentration. Level 3 studies may be able to confirm that similar effects to those seen in humans occur in aquatic organisms, but without a measure of the internal concentration it is not possible to relate these effects to the human therapeutic plasma concentration, and therefore determine if an aquatic organism is more, or less, sensitive to a particular drug. Studies at Levels 1 and 2 provide little or no relevant information.