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Toxicological information

Acute Toxicity: oral

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007
Reference Type:
other: summary of toxicity studies
Title:
Unnamed
Year:
2007
Report Date:
2007
Reference Type:
publication
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no death occurred
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:
A decrease in spontaneous motor activity was observed; this was reversible on the day of administration.
Body weight:
Body weight gains were significantly suppressed following administration in males (days 1-14) and females (days 1-3).
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.