Alcohols, C9-11-iso-, C10-rich

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

1992

Reference 2

Reference Type:

publication

Title:

Human health risk assessment of long chain alcohols

Author:

Veenstra G, Webb C, Sanderson H, Belanger SE, Fisk P, Nielsen A, Kasai Y, Willing A, Dyer S, Penney D, Certa H, Stanton K, Sedlak R.

Year:

2009

Bibliographic source:

Ecotoxicology and Environmental Safety

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

not specified

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dodecan-1-ol

EC Number:

203-982-0

EC Name:

Dodecan-1-ol

Cas Number:

112-53-8

Molecular formula:

C12H26O

IUPAC Name:

dodecan-1-ol

Constituent 2

Reference substance name:

1-Dodecanol

IUPAC Name:

1-Dodecanol

Details on test material:

Dodecanol is a 12 carbon long chain alcohol.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Male rats were exposed for a 37 days including the mating period.

Females rats were exposed from prior to mating through natural littering. Exposure ended at final sacrifice at day 5 postnatally.

Frequency of treatment:

Continuous

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1500 ppm (100 mg/kg/bw/day)
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
7500 ppm (500 mg/kg/bw/day)
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
30000 ppm (2000 mg/kg/bw/day)
Basis:
nominal in diet

No. of animals per sex per dose:

12

Control animals:

yes

Results and discussion

Results of examinations

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

reduction in mean white blood cell count for male rats (15%, 38%, and 32% reduction in the low-, mid-, and high-dose groups, respectively)

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

38% decrease in free cholestrol reported for mid-dose males; a 46% decrease in triglycerides in high-dose males)

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

1

Dose descriptor:

NOEL

Effect level:

< 1 500 ppm

Basis for effect level:

other: hematological (WBC) changes

2

Dose descriptor:

NOAEL

Effect level:

<= 30 000 ppm

Sex:

male/female

Basis for effect level:

other: No effect in macroscopic and histological examinations. No effect on BW, weight gain, food consumption and food efficiency.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Veenstra et al (2009) indicated the effects on white blood cell counts were of uncertain toxicologic significance because no alterations in differential cell counts were observed.

The observed changes in plasma chloesterol in mid-dose males were attributed to chance based on two outlier values included in the calculation of plasma cholestrol.

Veentra et al speculated the marginal effects on plasma cholestrol and triglyceride may be indicative of some biological effect on liver, but also indicated diet composition differences may have confounded some measured parameters.

Applicant's summary and conclusion

Executive summary:

24 rats (12 male and 12 female) were used in each dose group, which received 1-Dodecanol in the diet in concentrations of 0, 1500, 7500, and 30000 ppm (ca. 0, 100, 500 and 2000 mg/kg/bw/day) for a period of 37 days or longer. 1-Dodecanol had no influence on body weight, weight gain, food consumption and food efficiency in either sex at the doses employed. All pathological and histopathological findings were considered incidental, and not related to the dosing. The total number of white blood cells was reduced dose dependently, but no differences in differential count of the white blood cells could explain this effect. Mean white blood cell counts were 7.0 in the control group, 5.9 at 100 mg/kg, 4.3 (P<0.001) at 500 mg/kg and 4.7 (P<0.01) in the 2000 mg/kg groups. A statistically significant reduction was observed in plasma free cholesterol in the 500 mg/kg/bw/day group (from a mean of 0.18 in controls to 0.11 (P<0.05), and in triglyceride in the 2000 mg/kg/bw/day group( from a mean of 0.58 in controls to 0.31 (P<0.01). The reduction in free cholesterol seen in the 500 mg/kg group may be explained by two outliers with much lower concentrations than the remainder of that group.