3,7-dimethyloctane-1,7-diol

Endpoint summary

Description of key information

The aim of the study was to obtain information on the toxicity of Hydroxycitronellol in rats when given by oral administration via gavage daily for 28 days. The rats were treated with 100, 300 or 1000 mg Hydroxycitronellol/kg b.w./day. The control animals received the vehicle (Labrasol). No deaths occurred during the course of the study. All animals survived until scheduled necropsy. No test item-related changes were observed in behaviour or external appearance, during detailed clinical observations or for any of the parameter of the neurological screening, the body weight, body weight gain and body weight at autopsy, the food and drinking water consumption, the haematological, coagulation and clinical chemistry parameters, the eyes or optic region, the auditory acuity, the relative and absolute organ weights and at macroscopic inspection at necropsy and at histopathological examination at any of the tested dose levels. The faeces of all animals were of a normal consistency throughout the study. In conclusion, under the present test conditions of this study, the NOAEL (No-Observed-Adverse-Effect-Level) is above 1000 mg Hydroxycitronellol/kg b.w./day when given by oral administration as a Labrasol formulation via gavage daily for 28 days.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017 to 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008-10

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Specific details on test material used for the study:

Designation: Hydroxycitronellol
Batch no.: BM 7/17
Lot no.: 239/17
Characteristics: Clear colourless, viscous liquid; floral, green, sweet odour
Expiry date: 2019-06-14
Content: 99.7% area GC

Species:

rat

Strain:

other: CD®

Details on species / strain selection:

The rat was selected because of its proven suitability in toxicology studies and to comply with regulatory requirements for testing in a rodent animal species.

Sex:

male/female

Details on test animals or test system and environmental conditions:

CD® rats supplied by Charles River Laboratories Germany GmbH were used in this study. The body weight range did not exceed 10% of the mean weight for each sex at the time of selection. An initial health check was performed upon delivery of the animals.
Species / Strain / Stock: Rat / CD® / Crl:CD(SD)
Breeder: Charles River Laboratories Germany GmbH, Sulzfeld, Germany
Body weight: 205 - 366 g
Age: 59 days
Adaptation period: 5 days
Diet: ad libitum
Water: ad libitum

The animals were kept singly in MAKROLON cages (type III plus).
Room temperature: 22°C ± 3°C
Relative humidity: 55% ± 10%
The rooms were lit and darkened for periods of 12 hours each.

Route of administration:

oral: gavage

Vehicle:

other: Labrasol

Details on oral exposure:

Administration volume: 2 mL/kg b.w./day
The administration formulations were freshly prepared every day by diluting the test item in the vehicle to the appropriate concentrations. Test item formulations were prepared with concentrations of 50, 150 or 500 mg Hydroxycitronellol/mL Labrasol.
The test item was administered orally at a constant volume per kilogram body weight once daily for 28 days. The dose of the test item was adjusted to each animal's body weight daily.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The results indicate that all test item formulations were correctly prepared by LPT, and were stable for at least 24 hours. The measured concentrations ranged from 92.0% to 101.5% in the test item formulation samples.

Duration of treatment / exposure:

28 consecutive days

Frequency of treatment:

Once daily for 28 consecutive days

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5 animals/sex/group

Control animals:

yes, concurrent vehicle

Details on study design:

The dose levels for this study were based on the results of a 7-day dose-range finding study (LPT Study No. 35127). In this study, the animals were treated orally with 100, 300 or 1000 mg Hydroxycitronellol/kg b.w. daily for 7 days. The control group was treated with the vehicle (Labrasol) in the same way. None of the animals died prematurely during the course of the study. All male and female rats treated orally with 100, 300, or 1000 mg Hydroxycitronellol/kg b.w. daily for 7 days revealed moderate salivation starting up to 5 minutes p.a. lasting 5 to 20 minutes from test days 4 onwards. The body weight and the food and drinking water consumption were not test item-relatedly influenced. At necropsy on test day 8, no macroscopic changes were observed.

Observations and examinations performed and frequency:

Clinical signs: daily
Neurological screening: at the end of the treatment period
Mortality: daily
Body weight: at group allocation (test day -5), on test day 1 (before first administration), and daily during the treatment period for dose adjustment
Food consumption: on a weekly basis throughout the experimental period
Water consumption: daily
Laboratory examinations (haematology, clinical chemistry): Blood samples were collected from all animals at the end of the treatment period on test day 29
Ophthalmological and auditory examinations: Examinations were performed predose and at the end of the treatment period (test day 25)

Sacrifice and pathology:

On test day 29 (approx. 24 hours after the last administration), the animals were euthanized and inspected macroscopically. The histopathological examination included all relevant organs of the control and high dose group.

Statistics:

Standard statistical methods were used.

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:

no effects observed

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):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

behaviour (functional findings)

body weight and weight gain

clinical biochemistry

clinical signs

food consumption and compound intake

food efficiency

gross pathology

haematology

histopathology: neoplastic

histopathology: non-neoplastic

mortality

ophthalmological examination

organ weights and organ / body weight ratios

water consumption and compound intake

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Conclusions:

Under the present test conditions of this study, the NOAEL is above 1000 mg Hydroxycitronellol/kg b.w./day when given by oral administration as a Labrasol formulation via gavage daily for 28 days.

Executive summary:

The aim of the study was to obtain information on the toxicity of Hydroxycitronellol in rats when given by oral administration via gavage daily for 28 days. The rats were treated with 100, 300 or 1000 mg Hydroxycitronellol/kg b.w./day. The control animals received the vehicle (Labrasol). No deaths occurred during the course of the study. All animals survived until scheduled necropsy. No test item-related changes were observed in behaviour or external appearance, during detailed clinical observations or for any of the parameter of the neurological screening, the body weight, body weight gain and body weight at autopsy, the food and drinking water consumption, the haematological, coagulation and clinical chemistry parameters, the eyes or optic region, the auditory acuity, the relative and absolute organ weights and at macroscopic inspection at necropsy and at histopathological examination at any of the tested dose levels. The faeces of all animals were of a normal consistency throughout the study. In conclusion, under the present test conditions of this study, the NOAEL (No-Observed-Adverse-Effect-Level) is above 1000 mg Hydroxycitronellol/kg b.w./day when given by oral administration as a Labrasol formulation via gavage daily for 28 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The aim of the study was to obtain information on the toxicity of Hydroxycitronellol in rats when given by oral administration via gavage daily for 28 days. The rats were treated with 100, 300 or 1000 mg Hydroxycitronellol/kg b.w./day. The control animals received the vehicle (Labrasol). No deaths occurred during the course of the study. All animals survived until scheduled necropsy. No test item-related changes were observed in behaviour or external appearance, during detailed clinical observations or for any of the parameter of the neurological screening, the body weight, body weight gain and body weight at autopsy, the food and drinking water consumption, the haematological, coagulation and clinical chemistry parameters, the eyes or optic region, the auditory acuity, the relative and absolute organ weights and at macroscopic inspection at necropsy and at histopathological examination at any of the tested dose levels. The faeces of all animals were of a normal consistency throughout the study. In conclusion, under the present test conditions of this study, the NOAEL (No-Observed-Adverse-Effect-Level) is above 1000 mg Hydroxycitronellol/kg b.w./day when given by oral administration as a Labrasol formulation via gavage daily for 28 days.