Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 237-159-2
CAS number: 13674-87-8
The results obtained in a two year carcinogenicity study (Stauffer Chemical Company, 1981a; Freudenthal, R.I. and Henrich, R.T., 2000) indicate possible concern for man due to the development of adenomas (renal, hepatocellular and adrenal) in addition to Leydig cell tumours in rats.
TDCP is classified as Carc. Cat. 2 H351 " suspected
causing cancer” based on the results of the above carcinogenicity study
further supported by a non-genotoxic mode of action for carcinogenic
effects for TDCP.
In a 2-year carcinogenicity study, in which groups of 60 male and
60 females rats were fed diets containing TDCP to achieve dose levels of
0, 5, 20 and 80 mg/kg/day, there was a significant increase in the
incidence of renal cortical adenomas in mid and high dose animals at 24
months. There was no increase at 12 months. The incidence of benign
testicular interstitial cell tumours was also increased in the mid- and
high-dose animals at both 12 and 24 months. Hepatocellular adenomas and
adrenal cortical adenomas were statistically increased in the high dose
animals at 24 months.
In the testes, there was an
increased incidence of Leydig cell tumours in the mid and high dose
males at both 12 and 24 months. The mechanism by which TDCP induces such
tumours is not known. It is reported that one non-genotoxic mode of
action by which chemicals can induce such tumours is attributed to
alterations in the Hypothalmus-Pituitary-Testis (HPT) Axis which results
in elevated levels of luteinising hormone (LH). Increases in LH levels
have been shown to be necessary for the induction of Leydig cell tumours
through chronic stimulation of the Leydig cells. There are seven known
non-genotoxic hormonal mechanisms which have the potential to disrupt
the HPT axis leading to Leydig cell tumour induction. Two of these modes
of action are not considered of relevance to humans (GnRH antagonism and
dopamine agonism) (Clegg et al.,1997). However, the other five
mechanisms, (5 α-reductase inhibition, androgen receptor antagonism,
inhibition of testosterone biosynthesis, aromatase inhibition and
exogenous oestrogen agonism) have been considered to be potentially
relevant to humans.
Overall, while the mode of
action by which these tumours are induced cannot be identified, there
may be some concern for man regarding their formation.
A LOAEL of 5 mg/kg/day is
based on the hyperplasia of the convoluted tubule epithelium with
increased incidences observed in all treated male animals and in high
dose females at 24 months. Hyperplasia was observed from the lowest dose
tested. Hyperplasia is often considered as a pre-neoplastic lesion,
which can lead to tumour formation. The study report does not provide
enough detailed information to conclude whether the hyperplasia observed
following treatment with TDCP would progress to cancer or whether the
tumours observed with TDCP arise through a different mechanism. However,
it is not unreasonable to assume that the tumours have developed through
There is some evidence to
suggest that TDCP is mutagenic in vitro. However, in vivo
mutagenicity studies were negative, indicating that, in vivo,
TDCP is non-genotoxic. This indicates that TDCP may be assumed to be a
In a study carried out to
look at the mortality experience of worker in a TDCP manufacturing
plant, there was a higher than expected number of lung cancers among
male workers. However, the report concluded that there was no evidence
linking these lung cancers with exposure to TDCP. There were no other
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Sellel veebilehel kasutatakse küpsiseid, et tagada lehe parim kasutus.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again