Chloroform

Long-term toxicity to fish

Description of key information

Only one valid study on the long-term toxicity of chloroform to fish has been found, which is on the Japanese Medaka fish. The NOEC conncentration established for long-term exposure of Medaka fish to chloroform was 1.463 mg/L based on lesions found in the gallbladder and the bile duct.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

1.463 mg/L

Additional information

The discussion is mainly based on the draft of the European Union Environmental Risk Assessment for chloroform prepared by France (2007), section 3.2.1.1 (pages 87-88):

The chronic toxicity study of Toussaint et al. (2001) used 14-day old fry Japanese Medaka fish (Oryzias latipes) that were continuously exposed to chloroform in a flow-through system for 6 and 9 months. Test solution concentrations were analytically verified. Endpoints were growth, survival, hepatocarcinogenicity, hepatocellular proliferation, histopathology, and intrahepatic chloroform concentrations.

In Medaka exposed to chloroform concentrations from 0.017 to 1.463 mg/L, induction of liver neoplasms due to chloroform exposure was not significantly different in treated fish when compared to control fish, after 6 or 9 months of exposure, respectively. Chloroform was not hepatocarcinogenic to Medaka after 6 or 9 months of exposure, respectively.

Histopathological effects were seen after 6 and 9 months of exposure to 1.463 mg/L consisting of lesions of the gallbladder and abnormalities of the bile ducts. Males tended to be less sensitive to exposure to 1.463 mg/L for 6 months showing only significant increase in proliferation or hyperplasia of the bile ducts of the liver. At the same time point and exposure concentration, female fish exhibited nine significant findings in the bile ducts of the liver and the gallbladder (bile duct hyperplasia, bile duct epithelium hyperplasia, dilatation of the bile ducts, concretions in the lumen, inflammations around the bile ducts, concretions in the lumen of the gallbladder, gallbladder and cystic duct hyperplasia and cystic duct dilatation).

After 9 months of exposure, males exhibited higher incidence of dilatation of the cystic duct of the gallbladder and a tendency toward a significantly higher incidence of epithelium hyperplasia of the gallbladder. At exposure to 1.463 mg/L, females responded with a higher incidence for 3 of the 9 endpoints already significantly affected after 6 months of exposure plus a significant effect on the inflammation of the wall of the gallbladder. At exposure concentrations of 0.151 mg/L, these hepathological findings were not found to occur at such a high incidence (only bile duct dilatation was found at a higher incidence after 9 months of exposure).

Pathology findings were dissimilar between this study and other mammalian studies. As an example, biliary concretions that were observed in mammalians are usually caused by infection while in the case of fish, the reason for the occurrence of concretions in the gallbladder and the bile ducts is unknown. These dissimilarities could be attributed to the different routes of exposure, different exposed concentrations and to the choice of the animal model.

In conclusion, the study of Toussaint et al. (2001) demonstrated that a chronic exposure of Medaka fish to a chloroform concentration of 1.463 mg/L is causing significant effects on the histopathology of the gallbladder (lesions) and the bile ducts (abnormalities). Although these findings should be ecotoxicologically significant, this effect concentration will be considered as a NOEC because of the very specific effects that were observed at this concentration and the uncertainty about effects at the population level (it is not proven that there might be effects on population level with longer exposure periods).

In conclusion, the NOEC of 1.463 mg/L will be considered in this risk assessment to take into account the abnormalities and all other effects that occurred in the tested fish.