2-ethylhexane-1,3-diol

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published in a peer-reviewed journal

Data source

Reference

Reference 1

Reference Type:

other company data

Title:

Unnamed

Year:

1989

Report date:

1989

Reference 2

Reference Type:

publication

Title:

Toxicology Update 2-Ethyl-1,3-hexanediol

Author:

Ballantyne B

Year:

2005

Bibliographic source:

J. Appl. Toxicol 25: 248-259

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

dosed 5 days per week

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexane-1,3-diol

EC Number:

202-377-9

EC Name:

2-ethylhexane-1,3-diol

Cas Number:

94-96-2

Molecular formula:

C8H18O2

IUPAC Name:

2-ethylhexane-1,3-diol

Test material form:

liquid: viscous

Details on test material:

no data available

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data avaialble

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days, 21 doses

Frequency of treatment:

once daily, 5 days per week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1000 mg/kg bw/d
Basis:
no data

Doses / concentrations 2

Remarks:

Doses / Concentrations:
300 mg/kg bw/d
Basis:
no data

Doses / concentrations 3

Remarks:

Doses / Concentrations:
100 mg kg/bw/d
Basis:
no data

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

Administered intragastrically by gavage, 5 days per week for 21 treatments within 28 days.

Examinations

Observations and examinations performed and frequency:

Clinical signs, body weights, food consumption, hematology, clinical chemistry and gross and microscopic pathology

Sacrifice and pathology:

Gross pathology and histopathology examinations performed

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight gains for males in the 300 and 1000 mg/kg bw/d groups were lower but not statistically significantly; this amounte to a 9 and 6% lower weight gain. Body weights of females were unaffected

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption was slightly increased over the controls for the 100 and 1000 mg/kg bw/d groups.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Increased leukocyte counts in females at 300 and 1000 mg/kg bw/d. Differential leukocyte counts were unaffected. Platelet counts were significantly decreased in 1000 mg/kg bw/d females. No effects in males.

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Relative and absolute liver weights were increased for high dose females. Relative liver weights were increased for high dose males. Mean relative spleen weight was increased for high dose males.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Increased liver weights were not assoicated with any morphological or biochemical indications of organ damage.

Details on results:

There were no mortalities or signs of toxicity. Body weights of females were unaffected but mean body weights of the males of the 300 and 1000 mg/kg bw/d groups were lower, although not statistically significantly, than the controls on days 21 and 28. Body weight gains for these males were, respectively, 9% and 6% lower. Food consumption was slightly increased over the controls for the 100 and 1000 mg/kg bw/d groups. Leukocyte counts were higher in a dose-related manner for all female EHD groups, but with statistical significance only for the 300 and 1000 mg/kg bw/d groups; differential leukocyte counts were unaffected. Platelet counts were statistically significantly decreased for the 1000 mg/kg bw/d EHD females. Clinical chemistry was not affected compared with controls. Relative and absolute liver weights were increased for the 1000 mg/kg bw/d females and relative liver weights were increased for the 1000 mg/kg bw/d males. Mean relative spleen weight was increased, compared with the controls, for the 1000 mg/kg bw/d males. No dosage-related gross or microscopic pathology was seen. The increased liver weights were not associated with any morphological or biochemical indications of organ damage, and it is therefore most likely an adaptive response to the metabolism of EHD.

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Increased leukocyte counts, dose-related, in mid- and high-dose females; decreased platelet counts in high dose females. Liver weight effects in high dose females and males.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The repeated dose toxicity of oral 2-ethylhexane-1,3-diol dosing (100, 300 and 1000 mg/kg bw/d) was studied in rats for 28 days. No deaths or signs of significant toxicity, including histopathologic findings, occurred. The oral NOAEL was 100 mg/kg bw/d, based on the observation of liver weight changes and minor hematologic findings at 1000 mg/kg bw/d, and hematologic effects in mid- and high-dose females.