Hexane-1,2,6-triol

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: oral

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Data source

Reference

Reference Type:

publication

Title:

Experimental Toxicity and Metabolism of 1,2,6-Hexanetriol

Author:

Smyth HF et al.

Year:

1969

Bibliographic source:

Toxicol. Applied Pharmacol., 15: 282-86

Materials and methods

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexane-1,2,6-triol

EC Number:

203-424-6

EC Name:

Hexane-1,2,6-triol

Cas Number:

106-69-4

Molecular formula:

C6H14O3

IUPAC Name:

hexane-1,2,6-triol

Test material form:

liquid

Details on test material:

QSAR method by using calculation

Test animals

Species:

rat

Strain:

other: CFN

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Strain: Rat / CFN
- Number and sex: 432 animals (216 males and 216 females)

ENVIRONMENTAL CONDITIONS:
- Diet: Purina ® Laboratory Chow Meal
- Water: tab water ad libitum
- Housing in groups of 4 animals of the same sex in wire-bottom galvanized cages

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

Food consumption was measured for each cage by 28-day periods.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 years

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.25 other: % in diet

Doses / concentrations 2

Dose / conc.:

0.5 other: % in diet

Doses / concentrations 3

Dose / conc.:

1 other: % in diet

Doses / concentrations 4

Dose / conc.:

2 other: % in diet

Doses / concentrations 5

Dose / conc.:

5 other: % in diet

No. of animals per sex per dose:

36 males and females per dose, 20 males and females per dose were treated for the full 2-year period

Control animals:

yes, concurrent no treatment

Details on study design:

Four to 8 of each sex at each dosage level were designated in advance for sacrifice after 6, 9, and 12 months. Twenty of each sex were maintained until death or for the entire period.

Examinations

Observations and examinations performed and frequency:

Rats were weighed biweekly for 1 month, then every 4 weeks. All animals dying were autopsied to judge cause of death. Hematocrit values were determined 6 times on 10 male rats receiving the 2 highest and the control dosages.

Sacrifice and pathology:

From rats dying spontaneously and from all rats sacrificed, sections of 17 tissues were taken for microscopic study. Tissues were fixed in buffered formalin. All tissues were studied only from control rats and those on 5 % diets. In addition to hematoxylin and eosin stain applied to all, selected liver and kidney sections were stained for lipoid droplets with Sudan IV, and with periodic acid-Schiff stain for reticulin fibers. Selected Iivers were stained with Best's carminic acid stain for glycogen. Selective spleen sections were stained with Turnbull Blue for hemosiderin, and pancreas tissues for beta-cell changes using the Liisberg chromotrope 2R-phosphotungstic acid technique.

Statistics:

All numerical data were evaluated by Student's t-test, analysis of variance, or chi square with Yate's correction for continuity as appropriate.

Results and discussion

Results of examinations

Mortality:

mortality observed, non-treatment-related

Description (incidence):

No rat died of toxic eff ect, evidence of a sufficient infection or accident being found for each victim.

Survivors among 40 rats in each group after an exposure period of 2 years were fewest among controls (15), greatest among those with 0.5 % test item in the diet (39), and intermediate at 5 % in the diet (22). Mean expectation of life at birth was not reduced by treatment, ranging from
633 and 694 days formale and female controls to 681 and 746 days at 5 % in the diet.

Body weight and weight changes:

not specified

Description (incidence and severity):

Body weight gain among males at 5 % in the diet was 90 % that of controls, a statistically significant reduction. Other groups did not differ from the controls.

Organ weight findings including organ / body weight ratios:

not specified

Description (incidence and severity):

After two years there was no significant difference from controls in mean weights ± standard deviations of liver or kidneys as a percentage of body weight.

However, there was a transient early effect on kidney but not liver weight, male kidneys being heavier than controls at 6, 9, and 12 months on 5% in the diet; female kidneys were heavier at 6, 9, and 12 months in 5%, 6 months at 2%, 6 and 9 months at 1%.

Histopathological findings: non-neoplastic:

not specified

Description (incidence and severity):

In the kidneys there was an increase in diffuse tubular cloudy swelling at 12 months in rats on 5, 2, and 1% not seen at other times or levels, and an increase in diffuse congestion of glomeruli at 12 months only in rats of the 5% group. In the livers there was diffuse parenchymatous cloudy swelling at 24 months in rats on 5 and 2% levels; and in the pancreas an increase in acinar cloudy swelling at 24 months on the 5% level.

Histopathological findings: neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Neoplasms were found in 44 of the 240 rats observed for 2 years of dosing or until earlier death. Twenty-one of these were the pituitary adenomas which were found increasingly often in CFN rats in different laboratories at the time (1960-62) the feeding study was done, 5 among controls, 2-4 in other groups. The remaining neoplasms were widely distributed in location and kind, equally among the dosage groups. The number of rats with neoplasms varied from 6 to 10 in the different dosage groups, 10 at the 5 % level, 9 in the control group.