RC - What is RC? - Rotterdam Convention

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studies, the compound induced unscheduled DNA synthesis in Syrian
hamster embryo fibroblast cultures but not in rat hepatocyte
cultures. It induced unscheduled DNA synthesis in rats in vivo,
but did not induce sex-linked recessive lethal mutations in
Drosophila melanogaster.
In the only long-term (2 years) study, in which rats received
diet containing hexachlorobutadiene at doses of 0.2, 2 or 20 mg/kg
body weight per day, an increased incidence of renal tubular
neoplasms was observed only at the highest dose level.
1.7.4 Mechanisms of toxicity
The nephrotoxicity, mutagenicity and carcinogenicity of
hexachlorobutadiene is dependent on the biosynthesis of the toxic
sulfur conjugate 1-(glutathion- S-yl)-1,2,3,4,4-pentachloro-
1,3-butadiene (GPB). This conjugate is mainly synthesised in the
liver and is further metabolized in the bile, gut and kidneys to
1-(cystein- S-yl)-1,2,3,4,4-pentachloro-1,3-butadiene (CPB). The
activation of CPB, dependent on cysteine conjugate ß-lyase, to a
reactive thioketene in the proximal tubular cells finally results
covalent binding to cellular macromolecules.
1.8 Effects on humans
No pathogenic effects in the general population have been
described.
There have been two reports of disorders among agricultural
workers using hexachlorobutadiene as a fumigant, but they were also
exposed to other substances. An increased frequency of chromosomal
aberrations was found in the lymphocytes of peripheral blood of
workers engaged in the production of hexachlorobutadiene and
reported to be exposed to concentrations of 1.6-12.2 mg/m 3 .
1.9 Evaluation of human health risks and effects on the
environment
1.9.1 Evaluation of human health risks
As there have been very few human studies, the evaluation is
mainly based on studies in experimental animals. However, limited
human in vitro data suggest that the metabolism of
hexachlorobutadiene in humans is similar to that observed in
animals.
Hexachlorobutadiene vapour is considered to be irritating to
the mucous membranes of humans, and the liquid is corrosive. The
compound should also be regarded a sensitizing agent.
The main target organs for toxicity are the kidney and, to a
much lesser extent, the liver. On the basis of short- and long-term
oral studies in rats and mice, the NOAEL is 0.2 mg/kg body weight
per day. In one short-term inhalation study in rats (12 days,