RC - What is RC? - Rotterdam Convention

administration to experimental animals, but the rate of absorption
following inhalation or dermal exposure has not been investigated.
In rats and mice, the compound distributes mainly to the liver,
kidneys and adipose tissue. It is rapidly excreted. Binding to
liver
and kidney protein and nucleic acids has been demonstrated.
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The biotransformation of the compound in experimental animals
appears to be a saturable process. This process proceeds mainly
through a glutathione-mediated pathway in which hexachlorobutadiene
is initially converted to S-glutathione conjugates. These
conjugates can be metabolized further, especially in the
brush-border membrane of renal tubular cells, to a reactive sulfur
metabolite, which probably accounts for the observed nephrotoxicity,
genotoxicity and carcinogenicity.
1.6 Effects on organisms in the environment
Hexachlorobutadiene is moderately to very toxic to aquatic
organisms. Fish species and crustaceans were found to be the most
sensitive, 96-h LC50 values ranging from 0.032 to 1.2 and 0.09 to
approximately 1.7 mg/litre for crustaceans and fish, respectively.
The kidney was demonstrated to be an important target organ in fish.
Based on several long-term tests with algae and fish species,
no-observed-effect level (NOEL) of 0.003 mg/litre was established;
this classifies the compound as very toxic to aquatic species.
End-points investigated include general toxicity, neurotoxicity,
biochemistry, haematology, pathology, and reproductive parameters.
In one 28-day early-lifestage test with fathead minnows,
reproduction was unaffected at concentrations of up to
0.017 mg/litre, whereas increased mortality and a decreased body
weight were observed at 0.013 and 0.017 mg/litre. The NOEL was
0.0065 mg/litre.
Only one reliable test with terrestrial organisms has been
described. In a 90-day test with Japanese quail, receiving a diet
containing the compound at concentrations from 0.3 to 30 mg/kg diet,
the survival of chicks was decreased at 10 mg/kg diet only.
1.7 Effects on experimental animals and in vitro test systems
1.7.1 General toxicity
Hexachlorobutadiene is slightly to moderately toxic to adult
rats, moderately toxic to male weanling rats, and highly toxic to
female weanling rats following a single oral dose. The major target
organs are the kidney and, to a much lesser extent, the liver.
Based on animal data, the vapour of hexachlorobutadiene is
irritating to mucous membranes and the liquid is corrosive. The
substance should be regarded as a sensitizing agent.
In the kidneys of rats, mice and rabbits, hexachlorobutadiene
causes a dose-dependent necrosis of the renal proximal tubules.