Alcohols, C16-17-branched and linear

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

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

Adequacy of study:

supporting study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions, on a related material. Report in German language, English summary page.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1985

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1999

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:

(no neurobehavioural testing; limited range of endpoints assessed in other examinations)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecan-1-ol

EC Number:

253-149-0

EC Name:

Hexadecan-1-ol

Cas Number:

36653-82-4

Molecular formula:

C16H34O

IUPAC Name:

hexadecan-1-ol

Details on test material:

- Name of test material (as cited in study report): hexadecan-1-ol (tradename Lanette 16)
- Molecular formula (if other than submission substance): C16-H34-O
- Molecular weight (if other than submission substance): 242.444
- Smiles notation (if other than submission substance): C(CCCCCCCC)CCCCCCCO
- InChl (if other than submission substance): 1/C16H34O/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17/h17H,2-16H2,1H3
- Structural formula attached as image file (if other than submission substance): see Fig 1
- Substance type: no data
- Physical state: no data
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: M 84-98 g; F 81-93g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
- no data

VEHICLE
- Justification for use and choice of vehicle (if other than water): not stated
- Concentration in vehicle: 0, 2, 10 or 20%
- Amount of vehicle (if gavage): 5 ml/kg bw
- Lot/batch no. (if required): no data
- Purity: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 500, and 1000 mg/kg bw
Basis:
other: nominal conc.

No. of animals per sex per dose:

10 (main study) + 5 (satellite groups)

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: reversibility
- Post-exposure recovery period in satellite groups: 28 days
- Section schedule rationale (if not random): no data

Positive control:

none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: clinical signs and mortality

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: Yes
- Time schedule for examinations: daily

FOOD EFFICIENCY: No data

WATER CONSUMPTION: Yes
- Time schedule for examinations: weekly

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: at end of study
- Dose groups that were examined: no data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 21/22 daily doses
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters examined.: Haematocrit, MCV, Hb, RBC, WBC, Thrombocytes, differential white count.

CLINICAL CHEMISTRY: Yes 
- Time schedule for collection of blood: After 21/22 daily doses
- Animals fasted: No data
- How many animals: No data
- Parameters examined: Serum urea, creatinine, Na, K, calcium, alkaline phosphatase, ALAT, ASAT, GT, bilirubin, chloride, albumin, total protein, cholesterol

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: thyroid, adrenals, thymus, kidney, spleen, heart, brain, testes, liver

HISTOPATHOLOGY: Yes, all organs from the control and top dose animals were examined plus the animals from the reversibility study.

Statistics:

T-test. U-test for organ weights

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No effects on mortality
Unremarkable other than top dose females appearing rather defensive when handled

BODY WEIGHT AND WEIGHT GAIN
No effects

FOOD CONSUMPTION
No effects

FOOD EFFICIENCY
No data

WATER CONSUMPTION
No effects

OPHTHALMOSCOPIC EXAMINATION
No effects

HAEMATOLOGY
No differences between treated and control animals other than an increase in neutrophils containing rodlike bodies observed in top dose females (confidence level 95%*). Values obtained (% rod like cells) were controls 2.5, low dose 3.3, mid dose 2.9, high dose 5.3*

CLINICAL CHEMISTRY
Statistically significant changes (*95% ** 99% confidence) in some clinical chemistry parameters were noted as follows:
- 500 mg/kg bw/day males increased potassium*,
- 500 mg/kg/day females increased GGT*, cholesterol** and chloride*
- glucose was elevated in top dose males (mmol/l): Control 6.03, Low  6.20, Mid 6.25, High 7.28**
These changes were not dose and/or sex related and not correlated with any histopathological findings and are therefore not considered of toxicological significance.

URINALYSIS
No effects

NEUROBEHAVIOUR
No data

ORGAN WEIGHTS
Both absolute and relative organ weights were essentially comparable in treated and control animals.
Sporadic changes were observed as follows (*95% ** 99% confidence):
- increase in absolute male kidney weight at 500 mg/kg/day*
- increase in absolute testis weight at 1000 mg/kg/day*; mean relative (absolute) testis weight: Control 0.856 (3.207), Low 0.839 (3.186), Mid 0.908 (3.455), High 0.893 (3.474*)
- the only change in relative organ weight was an increase in male adrenal weight at 1000 mg/kg/day*; mean relative (absolute) adrenal weight: Control 0.013 (0.050), Low  0.014 (0.054), Mid 0.014 (0.055), High 0.015* (0.058)

GROSS PATHOLOGY
No effects

HISTOPATHOLOGY: NON-NEOPLASTIC
No treatment related histopathological changes in test, control or reversibility groups.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not applicable

HISTORICAL CONTROL DATA (if applicable)
No data

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a reliable study, performed according to a protocol similar to OECD guideline 407, a 28-day oral NOAEL of 1000 mg/kg bw/day was determined in the rat. The study was performed in compliance with GLP.

Executive summary:

[In view of the structural and chemical similarities, it is considered that the results of this study can be used for read-across to Alcohols C16 -17 branched and linear.]