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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, no classification is warranted for carcinogenicity.

Considering the available data of the substance's constituents BPA and DEA there is insufficient evidence to suggest that the substance would be a human carcinogen. For BPA the recent EFSA evaluation (EFSA 2015) assessed the likelihood level for carcinogenic effects as equivocal ("unlikely to - as likely as not -"); previous evaluations (SCOEL 2014, EU RAR 2003/2008) came to the conclusion that there is no convincing evidence for carcinogenicity of BPA. With respect to DEA increased incidences of liver neoplasms and renal tubule adenoma were observed in mice only; in rats no oncogenic potential was revealed. The findings in mice might be caused by a non-genotoxic mode of action involving choline depletion. For the substance itself, recently conducted genotoxicity tests (bacterial and mammalian cell mutation assays (Ames and HPRT) and in vitro mammalian cell micronucleus test) revealed no indication for a genotoxic potential. Overall, based on the classification criteria (Reg. (EC) No 1272/2008) a classification for carcinogenicity would at current not be justified.

Additional information

Although carcinogenicity data are no standard requirement, an assessment of carcinogenicity is performed based on read across to the two main constituents of the substance 2,2'-iminodiethanol (DEA; CAS No 111-42-2) and 2,2-bis(4-hydroxyphenyl)propane (BPA; CAS No 80-05-7). These account for approx. 55 % of the substance (BPA ca. 15 %, DEA ca. 40 %). Two reaction products of DEA, formaldehyde and BPA (i.e. Mannich Bases) account for further 39 % of the substance (Mannich Base 1 ca. 26 %, Mannich Base 2 [two isomers] ca. 13 %). These Mannich Bases are structurally similar to BPA, but are larger molecules (i.e. BPA with one or two diethanolaminomethyl-substituents attached to the aromatic ring). A QSAR analysis (OECD toolbox, version revealed for these reaction products no specific finding except a predicted estrogen receptor binding based on the BPA core-structure. Overall, carcinogenicity data of BPA and DEA are considered relevant for the toxicological assessment of the substance and are discussed in the following.


For BPA and DEA summaries on carcinogenicity exist based on peer-reviewed chemical risk assessments, e.g. EU Risk Assessment Report and OECD SIDS Initial Assessment Report, respectively. These are taken into account in the following.


Concerning BPA the 2003 EU RAR concluded with respect to carcinogenicity: "There are no human data contributing to the assessment of whether or not BPA is carcinogenic, but a dietary carcinogenicity study in rats and mice concluded that BPA was not carcinogenic in either species because the tumour findings were not considered toxicologically significant. No inhalation or dermal carcinogenicity studies were available, although in repeat exposure inhalation toxicity studies, BPA did not exhibit properties that raised concern for potential carcinogenicity. Taking into account all the animal data available, it was concluded that the animal evidence suggests that BPA does not have carcinogenic potential."

The 2008 updated EU RAR concluded: "The new information on the potential carcinogenic and/or promoting effects of BPA in prenatal and neonatal rat models supports the original conclusion from the published report that BPA does not possess any significant carcinogenic potential."

Furthermore SCOEL 2014 concluded: "Thus, there is currently no convincing evidence of the carcinogenicity of BPA when exposed either during the adulthood or perinatally. However, as concluded by EFSA (2014) there are some data (including the data by Delclos et al 2014; see chapter Toxicity to reproduction) to raise some concern on BPA effects on mammary gland cell proliferation after pre- and perinatal exposure. Whether this is linked to increased cancer incidence at later life or not remains to be shown."

The EFSA Scientific Opinion (EFSA Journal 2015, 13 (1), 3978) concluded with respect to proliferative and morphological changes potentially related to carcinogenesis:

"Earlier evidence for BPA effects on cell proliferation and differentiation in the mammary gland and other tissues (e.g. prostate or testis) has been supported by recent studies. The proliferative changes in the mammary gland reported in these new studies, including a non-human primate study, are however insufficient to conclude that there is a link to cancer development, although there might be a possible role of BPA in increasing the susceptibility to mammary gland carcinogenesis in later life."

• "The proliferative responses and possibly enhanced sensitivity to mammary gland carcinogens seen in animal studies might be of relevance for human health and are therefore included in the risk assessment."

• "Using a WoE approach, the CEF Panel assigned a likelihood level of “likely” to BPA induced proliferative changes in the mammary gland. Therefore, this endpoint was brought forward for hazard characterisation and for uncertainty analysis."

• "The CEF Panel considered that the evidence for proliferative changes induced by BPA in other organs (e.g. prostate or testis) is currently too limited to reach any conclusion."

With respect to carcinogenicity EFSA concluded:

“Very few epidemiological studies published to date have investigated a possible association between exposure to BPA and incidence of certain cancers, specifically breast cancer and meningioma. These studies do not allow any conclusion to be drawn regarding the carcinogenicity of BPA in humans."

• "BPA was not carcinogenic in two standard oral carcinogenicity studies in rats and mice. In a more recent study, female but not male mice, exposed to approximately 10 mg/kg bw per day BPA from in utero up to postnatal day (PND) 21, developed significantly more hepatocellular tumours (adenomas and carcinomas together) with or without preneoplastic lesions after a stop-exposure period of 10 months. Additional rodent studies on perinatal exposure to BPA investigated the potential carcinogenic effect in mammary gland. Due to weaknesses in these studies the results do not provide convincing evidence that BPA is carcinogenic to the liver during adult life or in mammary gland following perinatal exposure."

• "Using a WoE approach, the CEF Panel assigned a likelihood level of “unlikely to - as likely as not -” to carcinogenic effects of BPA. Since the likelihood level for this endpoint is less than "as likely as not” (...), this endpoint was not taken into account in the evaluation of uncertainty for hazard characterisation and risk characterisation."


The carcinogenicity potential of the second constituent DEA is summarized in OECD SIDS, 2007/last updated in 2008:

"DEA formulated in ethanol showed no oncogenic potential in the rat after unoccluded daily dermal exposure for 2 years. In the dermal mouse carcinogenicity study using similar exposure techniques, there was an increased incidence of liver neoplasms in males and females at all doses tested and an increased incidence of renal tubule adenomas in males at the high dose level only. The liver tumours in mice were considered to be directly related to the observed increase in the cellular proliferation rate, which is due to the observed enzyme induction, weak peroxisome proliferation and choline depletion with subsequent disturbance of its metabolism. ..... Benign kidney tumours (adenomas) were only observed in male mice at the high dose level at a low incidence, when using serial sections. Based on the increased S-phase synthesis observed in this organ, it is conceivable that a similar non-genotoxic mode of action involving choline deficiency is responsible for the renal tubular adenomas.

In short term tests on carcinogenicity, DEA was not carcinogenic, when tested in the Tg.Ac transgenic mouse model up to topical dose levels exceeding the MTD. .....

Various mechanistic in vitro and in vivo studies identified that DEA induced choline depletion is the key event in the toxic mode of action. DEA decreased gap junctional intracellular communication in primary cultured mouse and rat hepatocytes, but all these events were prevented with choline supplementation. .....

..... Apparent differences in the susceptibility of two different mice strains (B6C3F1 > C57BL) were noted. B6C3F1 mice are extremely sensitive to non-genotoxic effects and are known to possess a relatively high incidence of spontaneous liver tumours. Moreover, chronic stimulation and compensatory adaptive changes of hepatocyte hypertrophy and proliferation are able to enhance the incidence of common spontaneous liver tumours in the mouse by mechanisms not relevant to humans."

A recent IARC evaluation (2013) listed DEA as possibly carcinogen to humans (Group 2B) and came to the conclusion that "there is inadequate evidence in humans for the carcinogenicity of diethanolamine."


Overall, there is insufficient evidence to suggest that the substance would be a human carcinogen. Additionally, no indication for a genotoxic potential at all was revealed for the substance, when recently tested in bacterial and mammalian cell mutation assays (Ames, HPRT) and in an in vitro mammalian micronucleus test (see chapter "Genetic toxicity").

Justification for selection of carcinogenicity via oral route endpoint:
None of the available read-across studies is selected here, since all are relevant for the assessment of carcinogenicity.