ECHA - European Chemical Agency over D5; baarmoeder- en darmtumoren in ratten.
5 HUMAN HEALTH HAZARD ASSESSMENT >> link werkt niet meer
A review of information related to human health is included in EA (2009) and a more recent review by the Scientific Committee on Consumer Safety (SCCS, 2010) is also available. D5 is not classified on the basis of carcinogenicity, mutagenicity or reproductive toxicity. The carcinogenic potential of D5 was assessed in a single inhalation study using F344 rats (details of the study are summarised in EA, 2009). No neoplastic changes were reported in the respiratory tract or in the liver in the study (these sites were identified as target tissues in repeated exposure studies), but there was an increased incidence of uterine endometrial adenomas and adenocarcinomas and a NOAEL of 40 ppm was identified. Mechanistic studies indicated that the uterine tumours arise because D5 acts as a dopamine agonist. Differences in the reproductive ageing process between humans and rodents mean that this mechanism is not relevant to humans, but it could be relevant to other mammal and bird species. EA (2009) suggested that because the carcinogenic effect occurs late in life, it is not an effect that influences the sustainability of a population in a general sense, and therefore it was not necessary to take the carcinogenicity of D5 into account in a risk assessment for secondary poisoning of wildlife exposed via the food chain.
The main mammalian toxicological effect of concern identified for the secondary poisoning assessment was enlargement of the liver. This is thought to occur by a mechanism (a phenobarbital-type enzyme induction response) that is not relevant to humans, but the effects are considered relevant to wildlife (see EA (2009) for a detailed discussion). The NOAEL for these effects is thought to be around 19 mg/kg bw/day. No functional or histopathological changes to the liver accompany the liver weight changes.
(The highest concentrations of radioactivity (>30 μg equiv/g) immediately following exposure (0 hr) for male and female rats in the 160 ppm exposure group were in the small and large intestines, stomach, lung, adrenal gland, and liver. D5 was excreted in urine and faeces is approximately equal proportions. However, it appears that parent D5 is excreted in faeces, whereas excretion in the urine is of a metabolite (not identified).
Geen informatie over blootstelling van D5 bij mensen
Geen informatie over blootstelling van D5 bij mensen. Leververgroting bij ratten >>
4.4.5 Repeated dose toxicity
There is no information about the effects of repeated exposure to D5 on humans. Repeated exposure studies in animals are available for all relevant routes of exposure In relation to systemic effects, the main concern is liver enlargement and associated hypertrophy caused by phenobarbital-type enzyme induction (see Section 22.214.171.124). A NOAEL of 28 ppm (435 mg/m3) was identified for the inhalation route from a 90 day study in rats and a LOAEL of 25 mg/kg/day was identified for the oral route from a 14 day study in rats.
Memorandum Office of Environmental Health Hazard Assesment
OEHHA (2007, 2008a) concluded that concerns for potential carcinogenicity relevant to humans cannot be ruled out for D5. A rat-specific mechanism for the uterine tumors induced by D5 has been proposed by Dow Corning and the Silicones Environmental
Health and Safety Council (SEHSC). OEHHA found this mechanism, which hypothesizes dopamine agonism by D5, plausible but still uncertain (see OEHHA, 2007 and 2008a for a full discussion). OEHHA has found no new information that would alter our earlier findings. Concerns for the potential carcinogenicity of D5 remain. >>