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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

No Data on DIBC are available for the carcinogenicity endpoint. However data on a surrogate substance (MIBK) is available and this is discussed here.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
2 694 mg/m³
Study duration:
Quality of whole database:

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.

Additional information

The carcinogenicity of methyl isobutyl ketone (MIBK) was evaluated in 2-year carcinogenicity and chronic toxicity studies in rats and mice (NTP, 1987; Stout et al., 2008). These GLP studies were equivalent to OECD test guideline 451.

MIBK was administered by inhalation at nominal concentrations of 0, 450, 900, or 1800 ppm to F344N rats for 2 years, 6 hours/day, 5 days/week (50 rats/sex/group). On average, animals were necropsied at week 110. All animals underwent complete gross necropsy and microscopic examinations. Survival was decreased in the 1800 ppm males compared to control males. There were no differences in survival noted in females. Mean body weights in the 900 and 1800 ppm males rats were noted to be 6-8% and 5-8% less, respectively, after week 89 compared to controls; however, there were no differences in mean body weights noted in female rats. Chronic progressive nephropathy (CPN) similar to that which occurs in aged rats was observed in males and females in all groups, including controls, but increased in incidence in 1800 ppm male rats and in all MIBK-exposed female rats, and was more severe in all MIBK-treated male rats and 1800 ppm female rats. The incidence and severity of mineralization of the epithelium of the collecting ducts, a finding commonly accompanying CPN, were increased in male MIBK groups.   Hyperplasia of the transitional epithelium lining the renal pelvis was increased in treated males, achieving statistical significance at 900 and 1800 ppm. An increase in adenoma and adenoma or carcinoma (combined) was noted in male rats at 1800 ppm.  This increase in renal tubular tumors was considered possibly a result of the increase in severity of CPN and an alpha-2u-globulin-related mechanism by the study authors, the latter which is specific to male rats and is not considered relevant to humans. However, since CPN was exacerbated in females, additional mechanisms may be involved. The authors of the study also indicated that there is no human counterpart to CPN. Renal mesenchymal tumors were identified in 2 female rats in the 1800 ppm group. The relationship of the mesenchymal tumours to MIBK was uncertain. An increase in mononuclear cell leukemias in male rats was noted, achieving statistical significance and exceeding historical ranges for controls in the 1800 ppm group; however, the strength of the response (25/50 at 0 ppm vs 35/50 at 1800 ppm) made the finding uncertain. Adrenal medulla hyperplasia also was significantly increased in male rats at 1800 ppm (0 ppm, 13/50; 450 ppm, 18/48; 900 ppm, 18/50; 1800 ppm, 24/50). There also were exposure-related increases in benign or malignant pheochromocytoma (combined) of the adrenal gland in male rats (0 ppm, 8/50; 450 ppm, 9/48; 900 ppm, 11/50; 1800 ppm, 14/50). However, these increases were not significant and were within the historical ranges for chamber controls from inhalation studies fed NTP-2000 diet (69/398, 17±7%; range 10–28%), although the incidence in the 1800 ppm group was at the upper limit of the historical range. Based on these findings a NOAEC was not identified by the study authors. Review of the study data suggests that a NOAEC of 450 ppm can be derived for neoplastic and non-neoplastic lesions, based on the non-neoplastic lesions observed in the kidneys at higher dose levels and the irrelevance to humans of the tumour types observed in the kidneys of male rats. 

A subsequent study comparing the effects of 10-day oral administration of d-limonene (300 mg/kg bw/day), corn oil, or MIBK (1000 mg/kg bw/day) on Fisher 344 rat kidneys reported increased kidney weights and histological changes including hyaline droplet accumulation and increased alpha-2µ-globulin deposition in the renal cortex of male rats administered d-limonene or MIBK (Borghoff et al., 2009). These kidney findings were not observed in female rats. This study provides support that some of the renal findings in the Stout et al. (2008) study can be attributed to an alpha-2µ-globulin-related mechanism, which is not relevant to human risk assessment.


Supportive information on the carcinogenicity of MIBK was provided by the 2-year inhalational, carcinogenicity and chronic toxicity study in B6C3F1 mice, involving dose concentrations of 0, 450, 900, and 1800 ppm. No NOAEC was reported in this study due to dose-related histopathological findings of increased eosinophilic foci in the liver in MIBK-treated groups which achieved statistical significance at 450 and 1800 ppm. Treatment-related increases in multiple adenomas were noted in both male and female mice. Hepatocellular adenomas, and adenoma or carcinoma (combined) were increased in both sexes in the 1800 ppm group. As a result of these findings, a NOAEC was not reported by the study authors; however a review of the study data suggests that a NOAEC of 450 ppm can be derived for neoplastic and non-neoplastic lesions, based on the reported neoplastic effects in the liver of female mice at higher dose levels. Subsequent investigations (The Dow Chemical Company, 2009) reported that MIBK-related hepatocellular findings in mice may be due to induction of cytochrome P450 enzymes following activation of the mouse constitutive androstane receptor (CAR) in a manner that is similar to Phenobarbital-like compounds. The authors of the study noted that a carcinogenic effect in mice that can be attributed to Phenobarbital-like activation of CAR is not relevant to humans.

With respect to the other substances in this group ( MIBC, DIBC, DIBK), like MIBK they all have a complete set of genotoxicity data in vitro that demonstrate an absence of genotoxicity. As such, and as indicated above, the tumors observed in the above studies using MIBK appear to be initiated by a non-genotoxic mode of action (exacerbation of CPN, alpha 2u-globulin nephropathy, liver enzyme induction etc.). The relevance of these types of tumours to humans is limited due to species differences discussed above. Therefore it is not considered appropriate at this time to conclude that this group of substances represent a cancer risk to humans. In addtion, mode of action work is currently ongoing within the industry to re-affirm the lack of relevance of the tumors observed with MIBK in rats and mice to humans.

The NOAEC for cancer of 450ppm has been converted to mg/m3 for DIBC based on molecular wiehgt - the corrected NOEC is 2694 mg/m3.

Carcinogenicity: via inhalation route (target organ): digestive: liver