3,5,5-trimethylhexan-1-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study (see also: SIDS documents in section 13; Iuclid reference [27]; Reliability assigned: 1)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Reference 2

Reference Type:

other: summary of toxicity studies

Title:

Unnamed

Year:

2007

Report date:

2007

Reference 3

Reference Type:

publication

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,5,5-trimethylhexan-1-ol

EC Number:

222-376-7

EC Name:

3,5,5-trimethylhexan-1-ol

Cas Number:

3452-97-9

Molecular formula:

C9H20O

IUPAC Name:

3,5,5-trimethylhexan-1-ol

Details on test material:

- Analytical purity: 97.2 %
- Name of test material (as cited in study report): 3, 5, 5-trimethylhexan-1-ol
- Physical state: liquid
- Analytical purity: 97.2 %
- Source: Kyowa Yuka Ltd., Japan
- Lot/batch No.: 707173
- Stability under test conditions: confirmed
- Storage condition of test material: in the dark, air-tight containers, refrigerated

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan Charles River Co.
- Age at study initiation: 5-6 weeks old for both sexs
- Weight at study initiation: mean 156.7 g (149-165 g) for males; mean 133.9 g (126-144 g) for females
- Fasting period before study: 17 to 18 hours
- Housing: in groups of 5 animals in metal cages
- Accimatisation: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 3°C
- Humidity (%): 55 ± 10 %,
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 % test substance (w/v %)
- Amount of vehicle (if gavage): dose volume 5 mL/kg bw
- Lot/batch no. (if required):
- Purity: pharmaceutical grade (Japan Pharmacopoiea)


MAXIMUM DOSE VOLUME APPLIED:
5 mL/kg bw

Doses:

Definitive study: 2000 mg/kg bw
Selected based on results of preliminary study: 0, 500, 1000, and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily until day 14; animals were weighed on days 1, 3, 5, 10 and 14 after the drug was administered
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology (organs examined: liver, kidneys, spleen, heart, lungs, brain (cerebrum, cerebellum), stomach (anterior stomach, glandular stomach), duodenum, jejunum, ileum, cecum, colon, rectum and ovaries, testes, epididymis)

Statistics:

not needed

Results and discussion

Preliminary study:

There were no deaths in the preliminary study (i.e. LD50 was >2000 mg/kg bw); clinical sign (reduced movements) was seen after dosing, but was reversible within one day; significantly reduced body weight was seen in males throughout days 1-14, in females on days 1-3; there were no histopathological changes noted.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no death occurred

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no death occurred

Mortality:

No death occurred of either males or females

Clinical signs:

other: A decrease in spontaneous motor activity was observed; this was reversible on the day of administration.

Gross pathology:

No changes were detected on autopsy or histopathological examination.

Other findings:

- Histopathology: no changes noted
- Potential target organs: none identified

Any other information on results incl. tables

No deaths occurred of either males or females and the LD50 was estimated to be more than 2000 mg/kg bw. A reversible decrease in spontaneous motor activity was observed on the day of administration, and body weight gains were suppressed or tended to be suppressed from days 1 to 14 of administration in males and females. No changes were detected on autopsy or histopathological examination.

LD50: Male, > 2000 mg/kg bw; female, > 2000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 (oral, rat, 14 days) was >2000 mg/kg body weight. No target organ could be identified.

Executive summary:

The acute oral LD₅₀ (oral, rat, 14 days) of 3, 5, 5 -trimethylhexan-1-ol was >2000 mg/kg body weight in a study conducted according to OECD TG 401 and under GLP conditions using groups of 5 rats per sex and dose in a preliminary study (0, 500, 1000, 2000 mg/kg bw) and in the definitive study (2000 mg/kg bw).

No deaths occurred of either males or females. A reversible decrease in spontaneous motor activity was observed on the day of administration, and body weight gains were suppressed or tended to be suppressed from days 1 to 14 of administration in males and females. No changes were detected on autopsy or histopathological examination, i.e. a target organ could not be identified (Yoshimura et al., 2007).

The study is considered to be acceptable for assessment.