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EC number: 209-136-7 | CAS number: 556-67-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Specific investigations: other studies
Administrative data
Link to relevant study record(s)
Description of key information
There are a number of reliable studies that have mainly investigated the effects of D4 on the liver and induction of liver enzymes (Dow Corning Corporation, 1996d, 1998, 2002a,b, 2005a, Falany & Li, 2005, McKim et al., 2001b). There are also two reliable studies into the effects of D4 on the release of prolactin (Dow Corning Corporation, 2010a, b).
Additional information
Inhalation of D4 in rats lead to transient dose-dependent cell proliferation and sustained hypertrophy of the liver. Cell proliferation was at its maximum at Day 6 and then subsided until Day 27 of treatment. There was also an increase in thyroid weight and thyroid cell proliferation. These changes are similar to those observed with phenobarbital (Dow Corning Corporation, 2002b, McKim et al., 2001b).
There are five reliable studies that investigate hepatic enzyme activation by D4.
It has been demonstrated in vivo in rats that inhaled D4 acts like a phenobarbital-like inducer of hepatic microsomal enzymes in rats (Dow Corning Corporation, 1996d). This effect on hepatic enzymes has been further characterised in vitro (XenoTech, 1998) using human liver microsomes. D4 appeared to be a non-competitive inhibitor of human CYP2B6, CYP2D6 and CYP3A4/5; a competitive inhibitor of human CYP1A2; either a competitive or non-competitive inhibitor of CYP2C19. D4 had little or no capacity to inhibit rat CYP1A2 and human CYP2A6, CYP2C9 and CYP4A9/11 activity or to function as a metabolism-dependent (reversible or irreversible) inhibitor of any of the P450 enzymes examined, with the possible exception of rat CYP1A1/2 and human CYP3A4/5 which were weakly inhibited by D4 in a reversible metabolism-dependent manner. D4 appeared to be non-competitive inhibitor of rat CYP2B1/2. Another in vitro study noted that the constitutive androstane receptor (CAR) is a nuclear receptor that has been shown to be a key regulator in phenobarbital-induced up-regulation of CYP2B1/2 gene expression. and that the in vivo induction of CYP2B1/2 expression by D4 suggests the possibility that D4 is an activator of CAR in the rat (Dow Corning Corporation, 2005a). Species selectivity for the hepatic responses has been investigated in a study on rats and guinea pigs (Dow Corning Corporation, 2002a). It was shown that rats have an increase in liver weights following treatment with D4 or phenobarbital, but this was not the case for guinea pigs. The authors of the study concluded that in general, the findings of D4 in rat liver were similar to those observed with phenobarbital, but it was not clear if the effects of D4 were in response to D4, D4 metabolites or if the effects represent responses to D4-induced effects on some other organ system. It has also been demonstrated that D4 has different inductive properties in female rats of different ages and reproductive status, and that D4 administered to the pregnant dam is capable of inducing CYP expression in fetal liver and decreasing fetal body weight (Falany & Li, 2005).
There are two reliable studies that investigated the potential effects of D4 on serum prolactin concentrations (Dow Corning Corporation, 2010a, b). These studies showed that inhaled D4 did not decrease prolactin concentrations in Fischer 344 rats.
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