Diisodecyl sebacate

Carcinogenicity

Description of key information

No standard carcinogenicity studies are available on DIDS (or DIDA, DEHS or DOS). However, in a limited study, no treatment-related increase in the incidence of gross or microscopic lesions or abnormalities was seen in rats receiving about 10 mg DOS/kg bw/day (the study NOAEL) from the diet for up to 19 months (Le Breton, 1952-7). No evidence of tumour promoting activity was seen with DEHS in rats (Oesterle and Deml, 1988). 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

No data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study on a read-across compound, reported in the secondary literature (limited reporting). Only one (relatively low) dose level tested (about 10 mg/kg bw/day) (at least three dose levels are recommended by the OECD guideline) and testing conducted for up to 19 months (less than the recommended 24 months for rats)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats were fed for up to 19 months with DOS at 200 mg/kg via the diet. Only one (relatively low) dose level tested (about 10 mg/kg bw/day). Unspecified organs were examined for gross and/or microscopic lesions at necropsy. Possibly performed as part of a four-generation study; animals may have also been mated and/or exposed in utero over the course of the study.

GLP compliance:

no

Remarks:

predates GLP

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Up to 19 months

Frequency of treatment:

Presumably daily (given in the diet)

Post exposure period:

No data in citing sources

Remarks:

Doses / Concentrations:
200 mg/kg diet
Basis:
nominal in diet
(equivalent to about 10 mg/kg bw/day for adult rats, and 20 mg/kg bw/day for young rats)

No. of animals per sex per dose:

No data in citing sources

Control animals:

yes

Relevance of carcinogenic effects / potential:

No treatment-related increase in tumour incidence was observed. But only a single, relatively low, dose of 10 mg/kg bw was tested (3 dose levels are recommended by the relevant OECD guideline), and rats were only treated for up to 19 months (as opposed to the recommended 24 months).

Dose descriptor:

NOAEL

Effect level:

ca. 10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Conclusions:

Secondary sources briefly describe a pre-GLP chronic dietary study on DOS, a structurally-related read-across compound for DIDS. No treatment-related increase in the incidence of gross or microscopic lesions or abnormalities was seen in rats recieving about 10 mg/kg bw/day (the study NOAEL) from the diet for up to 19 months.

Executive summary:

A pre-GLP chronic dietary study has been conducted on DOS, a structurally-related read-across compound for DIDS, and is briefly reported in the secondary literature.

 

Wistar rats were fed DOS at the relatively low level of 200 mg/kg diet (about 10 mg/kg bw/day) for up to 19 months [no further details in citing sources; OECD guidelines recommend treatment with at least 3 dose levels for 2 years in rats].

 

Animals were subject to gross and histological examination upon necropsy [although the extent of this examination is not given]. No increased incidence of gross or microscopic lesions was reported, and the authors concluded that DOS lacked carcinogenic action.

 

The no-observed-adverse-effect level for carcinogenicity can therefore be considered about 10 mg/kg bw/day in this limited study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

No relevant carcinogenicity data were available on laboratory animals given repeated oral treatment with DIDS. Regarding read-across data, a limited chronic study with DOS is available, as is a tumour-promotion study on DEHS.

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

No data were available on DIDS (or DIDA), although QSAR analysis predicts that DIDS is not carcinogenic. In addition, no carcinogenic effects were seen in a limited study in which rats received DOS at about 10 mg/kg bw/day from their diet for 19 months, and no tumour promotion activity was seen for DEHS in a rat liver foci test . These findings indicate that DIDS does not warrant classification as a carcinogen under CLP Regulation (EC) 1272/2008 or the Dangerous Substances Directive 67/548/EEC.

Additional information

No standard carcinogenicity studies are available on DIDS (or DIDA, DEHS or DOS).

The OECD QSAR Toolbox identified no structural alerts for genotoxic or non-genotoxic carcinogenicity (by ISS) for DIDS. No carcinogenicity was predicted by QSAR models from the Danish EPA DB in male and female rats and mice (with TD₅₀ values of 1000 mg/kg bw/day) (OECD, 2012).

Relevant read-across data:

A pre-GLP chronic dietary study conducted on DOS is briefly reported in the secondary literature. Wistar rats were fed DOS at the relatively low level of 200 mg/kg diet (about 10 mg/kg bw/day) for up to 19 months [no further details in citing sources; OECD guidelines recommend treatment with at least 3 dose levels for 2 yr in rats]. Animals were subject to gross and histological examination upon necropsy [although the extent of this examination is not given]. No increased incidence of gross or microscopic lesions was reported, and the authors concluded that DOS lacked carcinogenic action. The NOAEL for carcinogenicity can therefore be considered about 10 mg/kg bw/day in this limited study (Le Breton, 1952-7).

No evidence of tumour promotion activity was seen in a rat liver foci test in which DEHS was orally administered to rats (5/sex/group) at 500 mg/kg bw, on three occasions per wk for 11 wk, following pre-treatment with a single oral administration of a known carcinogen (Oesterle and Deml, 1988).

References

Oesterle D and Deml E (1988). Promoting activity of di(2 -ethylhexyl) phthalate in rat liver foci bioassay. Journal of Cancer Research and Clinical Oncology 114, 133 -13

Justification for selection of carcinogenicity via oral route endpoint:
Limited chronic study on a read-across compound.