2-propylheptan-1-ol

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study (OECD) (No specific fertility study but treatment long enough to cover sperm maturation (no mating performed).)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 408 (Subchronic Oral Toxicity - Rodent: 90-day study, May 12, 1981)

Deviations:

no

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

2-propylheptan-1-ol

EC Number:

233-126-1

EC Name:

2-propylheptan-1-ol

Cas Number:

10042-59-8

Molecular formula:

C10H22O

IUPAC Name:

2-propylheptan-1-ol

Details on test material:

- Name of test material (as cited in study report): Propylheptanol
- Analytical purity: 99.5% (GC)
- Lot/batch No.: CIW/E, Reg. No. 20 595
- Test substance No.: 94/279
- Stability under test conditions: by reanalysis after the in-life phase of the study; the stability of the test substance in the vehicle over a period of 3 hours was proven before the start of the study (as the emulsions were prepared daily and administered within this time period, the stability was guaranteed)
- Homogeneity: proven by visual inspection
- Storage condition of test material: room temperature; protected from light

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH, Germany
- Age at study initiation: 42 days
- Weight at study initiation: the body weight of the males was in the range of 100 - 124 g (group mean: 110 g) and the body weight of the females was in the range of 85 - 101 g (group mean: 94 g)
- Housing: single
- Diet: ground Kliba maintenance diet rat/mouse/hamster, 343 meal, supplied by Klingentalmuehle AG, Kaiseraugst, Switzerland; ad libitum
- Water: drinking water (from water bottles) were available ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Cremophor EL(R) in bi-distilled water (approximately 5 mg/100 ml)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
To prepare the emulsion, Propylheptanol was weighed depending on the dose group, then the vehicle was filled up to the desired volume and subsequently mixed using an Ultra Turrax. During administration to the animals the test substance preparations were kept homogeneous with a magnetic stirrer. The test substance preparations were prepared daily.

The administration volume was 10 ml/kg body weight, based upon the latest individual body weight determination.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

At the beginning of the administration period the homogeneity of the test substance in the vehicle was checked at the low and high concentration; these analyses served also as concentration controls. Further concentration control analyses were carried out in samples from the mid dose drawn at the beginning of the administration period, and in samples from all doses drawn at the end of the administration period. Analytical checks of the concentrations revealed 89% - and 103% of the target concentrations. Although one value was only 89% of the target concentration (high dose at termination of the study), this was assessed as being acceptable.

Duration of treatment / exposure:

3 months

Frequency of treatment:

daily

Duration of test:

3 months

Doses / concentrations

Remarks:

Doses / Concentrations:
30, 150, 600 mg/kg bw/day
Basis:
nominal conc.

No. of animals per sex per dose:

10

Control animals:

other: yes, group #1: bi-distilled water, group #2: emulsifier (double distilled water with approx. 0.005% Cremophor EL)

Details on study design:

- Dose selection rationale:
Based upon the findings in a prenatal toxicity screening study with Propylheptanol (1580, 790 and 158 mg/kg body) the following doses were selected for the present study: 600 mg/kg body weight (as high dose with expected effects on body weight), 150 mg/kg body weight (as mid dose), 30 mg/kg body weight (as low dose)

Statistics:

Means and standard deviations of each test group were calculated. As two control groups were used in this study (groups 0 and 1), comparison was performed using either group 0 as the reference control group (with which groups 1 to 4 were compared) or group 1 was taken as the reference control group (with which groups 2 to 4 were compared).
Food consumption, body weight, body weight change, food efficiency: Parametric one-way analysis using the F-test (ANOVA) (two-sided). If the resulting p-value was equal or less 0.05, a comparison of each group with the control group using the DUNNETT's test (two-sided) was performed for the hypothesis of equal means.
Clinical pathology parameters, except differential blood count: Parametric one-way analysis using the F-test (ANOVA) (two-sided). If the resulting p-value was equal or less 0.05, a comparison of each group with the control group was performed using DUNNETT's tes (two-sided) for the hypothesis of equal means.
Urinalysis, except volume, color and turbidity: Pairwise comparison of each dose group with the control group using FISHER's exact test for the hypothesis of equal proportions.
Weight parameters: A comparison of each group with the control group using the DUNNETT's test (two-sided) was performed for the hypothesis of equal means.

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Remarks:

disregarding peroxisomal proliferation

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

2

Dose descriptor:

other: LOAEL disregarding peroxisomal proliferation

Effect level:

600 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: human hazard: impairment of food consumption/body weight/body weight change/terminal body weight, hematology, clinical chemistry, increase in squamous epithelial cells in the urine, histopathology

3

Dose descriptor:

NOAEL

Effect level:

30 mg/L air (nominal)

Based on:

test mat.

Sex:

female

4

Dose descriptor:

LOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: effects due to peroxisomal proliferation: increased mean relative liver weight, diffuse hypertrophy of the liver cells at 150 mg/kg bw

5

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

6

Dose descriptor:

LOAEL

Effect level:

600 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: impairment of food consumption/body weight parameters, hematology, clinical chemistry, urinalysis at 600 mg/kg bw, no effects on reproductive parameters; effects on liver due to peroxisomal proliferation

Observed effects

After a treatment period of 3 months covering the time of sperm maturation there was no effect on the reproductive organs examined by weight determinations and histopathological examinations.
Substance-related effects were seen at 600 mg/kg in both sexes and at 150 mg/kg in females, only. Main target organ was the liver, most probably related to a peroxisome proliferating potential of the test substance.