2-ethylhexane-1,3-diol

Carcinogenicity

Description of key information

No site-specific increase in tumour formation was observed after dermal treatment of EHD over a lifetime in mice.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Experimental data in a peer-reviewed journal

Qualifier:

no guideline available

Principles of method if other than guideline:

Precedes establishment of OECD guideline. The method was used previously by Hartwell, JL, 1951, Survey of Compounds Which Have Been Tested for Carcinogenic Activity, PHS publication 149, U.S. Government Printing Office, Washington, DC, USA.

GLP compliance:

no

Remarks:

Precedes establishment of GLP

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Epply colony, Epply Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE, 68105, USA.
- Age at study initiation: 7 weeks
- Randomized; litter mates were separated.
- 10/cage, in plastic cages with commercial bedding (San-i-cel, Paxton Processing Company, Inc., Paxton, IL, USA)
- Food: ad libitum, commercial diet (Wayne, Allied Mills, Chicago, IL, U.S.A.)
- Water: ad libitum

Route of administration:

dermal

Vehicle:

acetone

Details on exposure:

0.20 ml of chemical was applied to the shaved dorsal skin of the flanks in a 1-inch square area on mice (25 g). The 100% dose represents 752 mg/kg bw. Given twice weekly (once every 3.5 days), the dose is approximately 215 mg/kg/d).

Analytical verification of doses or concentrations:

not specified

Frequency of treatment:

Twice per week

Remarks:

Doses / Concentrations:
10, 50 and 100%
Basis:
nominal conc.
in acetone.

No. of animals per sex per dose:

50 per dose group in the treatment group. 50 animals served as vehicle control and positive control. 135 untreated animals also served as controls.

Control animals:

yes, concurrent vehicle

Details on study design:

The animals were checked weekly and all lesions and tumours were recorded. Animals were allowed to die spontaneously or were killed when moribund.

Positive control:

Yes, 7,12-dimethylbenzanthracene

Observations and examinations performed and frequency:

Animals were observed twice weekly.

Sacrifice and pathology:

Complete autopsies were performed on all animals. Histological examination was undertaken on the treated skin from all animals, all grossly observed tumors and other lesions in the lungs, livers, kidneys, etc. of treated and control animals. Formalin-fixed, paraffin-embedded specimens were cut and stained with hemotoxylin-eosin and other stains when needed.

Statistics:

The statistical significance of results was evaluated using the methods of Armitage, 1971.

Details on results:

In the skin, a slight local inflammatory change was noted. The lifespan of the EHD-treated mice did not differ significantly from that of the controls. Tumour incidences were not elevated over that of the vehicle controls.

Relevance of carcinogenic effects / potential:

Relevant for dermal low-dose applications or exposures.

Dose descriptor:

other: tumour incidence

Effect level:

215 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No differences from vehicle controls, but slightly increased over untreated controls.

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

The tumour incidence (%) for 2 -ethyl-1,3 -hexanediol (EHD), at 46 -64%, was increased above the untreated controls (42%), but

not over vehicle controls.

The incidence of tumors over untreated controls was not site-specific. The authors conclude that EHD did not produce a statistically-significant increase in cutaneous tumour incidence compared with untreated and positive control animals.

Conclusions:

In a dermal carcinogenicity study with Swiss mice involving applications twice weekly for a lifetime, EHD did not produce a statistically-significant increase in cutaneous tumour incidence compared with untreated and positive control animals. In combination with mutagenicity data, the substance is not considered a genotoxic carcinogen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

215 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

adequate, when genotoxicity is included.

Justification for classification or non-classification

The data do not meet the criteria for classification according to Regulation EC No. 1272/2008.

Additional information

In this study, the tumour incidence (%) in the highest dose of EHD, was slightly increased above the untreated controls, but

not over vehicle controls. The incidence of tumors over untreated controls was not site-specific.

The authors conclude that EHD did not produce a statistically-significant increase in cutaneous tumour incidence compared with untreated and positive control animals. Analysis by the U.S. EPA in 1981 found a positive

linear trend, and a site-specific chi-squared test indicated a possible oncogenic potential for EHD. However, they determined

the study to be inadequate for the purposes of determining the carcinogenic potential of EHD.

Justification for selection of carcinogenicity via dermal route endpoint:
experimental result