Registration Dossier

Diss Factsheets

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: The study was conducted according to OECD TG 423 (Acute Oral toxicity - Acute Toxic Class Method) under GLP conditions. The study is sufficient for endpoint evaluation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3,7,11-trimethyldodecyn-3-ol
EC Number:
216-510-3
EC Name:
3,7,11-trimethyldodecyn-3-ol
Cas Number:
1604-35-9
Molecular formula:
C15H28O
IUPAC Name:
3,7,11-trimethyldodec-1-yn-3-ol
Details on test material:
- Name of test material (as cited in study report): 3,7,11-trimethyldodecyn-3-ol
- Physical state: not reported
- Analytical purity: 99.0 area% (for details see analytical report No. 05L00028).
- Impurities (identity and concentrations):
- Purity test date: nor reported
- Lot/batch No.: 05-0001
- Stability under test conditions: The stability under storage conditions was confirmed by reanalysis (for details see analytical report No. 05L001 78).
- Storage condition of test material: not reported

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HanRcc:WIST(SPF) from RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland; female animals were nulliparaus and non-pregnant
- Age at study initiation: female animais approx 8- 12 weeks)
- Weight at study initiation: ± 20% of the mean weight
- Fasting period before study: Feed was withdrawn from the animais at least 16 hours before administration, but water was available ad libitum.
- Housing: in fully air-conditioned rooms; Stainless steel wire mesh cages, type DK-lll (Becker & Co., Castrop-Rauxel, FRG); Single housing
- Diet: ad libitum (Kliba-Labordiät (Maus 1 Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland,)
- Water: ad libitum (Tap water)
- Acclimation period: Acclimatization for at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 h /12 h (6.00 a.m. - 6.00 p.m. 1 6.00 p.m. - 6.00 a.m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/kg bw (10 g/100 mL substance); 2000 mg/kg bw (40 g/100 mL substance)
- Amount of vehicle (if gavage): 500 mg/kg bw (2 mL/kg); 2000 mg/kg bw (5 mL/kg)
- Justification for choice of vehicle: Olive oil Ph.Eur./DAB had to be used to ensure homogeneity of the preparation.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected. Therefore, a starting dose of 2,000 mg/kg bw body weight has been chosen in the first step with 3 female animals. As two of those animals died, 500 mg/kg bw were administered to 3 female animals in a second step. Because all animals survived the second step, 500 mg/kg bw have been tested in athird step with 3 female animals, finally.
Doses:
500 and 2000 mg/kg bw
No. of animals per sex per dose:
9 animals:
- 3 female animals at 2,000 mg/kg bw
- 6 female animais at 500 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Mortality:
- Two animais of the 2,000 mg/kg administration group were found dead on study days 3 and 5 respectively.
- No mortality occurred in the 500 mg/kg administration groups.
Clinical signs:
- Clinical observation in the 2,000 mg/kg bw administration group revealed impaired and poor general state, dyspnoea, lateral position, staggering, piloerection, smeared fur, diarrhea and lacrimation and were observed from hour 2 until including study day 3 after administration.
- Clinical observation in the 500 mg/kg bw administration group revealed impaired general state,
dyspnoea, staggering, piloerection and diarrbea and were observed from hour 1 until
including hour 5 after administration.
Body weight:
- The mean body weights of the 500 mg/kg bw administration groups increased throughout the study period.
- The body weight of the surviving animal of the 2,000 mg/kg bw administration group increased during the first post exposure observation week but did not increase during the second week.
This effect is observed at times in the rat strain used, because in the required age range the
female animals have already reached the phase of slow growth.
Gross pathology:
- The following macroscopic pathologic findings were observed in the animals that died: Few (2-5), black erosions/ulcers in the glandular stomach, diameter up to 4 mm (2,000 mg/kg bw: 1 female) and moderate, dark red or red discoloration of contents of small intestine (2,000 mg/kg bw: 2 females).
- No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study (2,000 mg/kg bw: 1 female; 500 mg/kg bw: 6 females).
Other findings:
- Organ weights:
- Histopathology:
- Potential target organs:
- Other observations:

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study the median lethal dose of 3,7,1 1-trimethyldodecyn-3-ol after oral administration was found to be greater than 500 mg/kg and less than 2,000 mg/kg bw in rats.
Executive summary:

The study was conducted according to OECD TG 423 (Acute Oral toxicity - Acute Toxic Class Method) under GLP conditions. The study is sufficient for endpoint evaluation. Acute oral toxicity was tested in female Wistar rats (3 per treatment group) via gavage.

Single doses of 2,000 and 500 mg/kg bw of test material preparations in olive oil were given to three administration groups of three fasted female animals, each, (2,000 mg/kg bw in 3 females, 500 mg/kg bw in 6 females) by gavage in a sequential manner. Two animals of the 2,000 mg/kg bw administration group were found dead from study day 3 until including study day 5. No mortality occurred in the 500 mg/kg bw administration groups.

Clinical observation in the 2,000 mg/kg bw administration group revealed impaired and poor general state, dyspnoea, lateral position, staggering, piloerection, smeared fur, diarrhea and lacrimation. Findings were observed from hour 2 until including study day 3 after administration. Clinical observation in the 500 mg/kg bw administration groups revealed impaired general state, dyspnoea, staggering, piloerection and diarrhea. Findings were observed from hour 1 until including hour 5 after administration. The mean body weights of the 500 mg/kg bw administration groups increased throughout the study period. The body weight of the surviving animal of the 2,000 mg/kg bw administration group increased during the first post exposure observation week but did not increase during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.

During necropsy findings in the animals that died in the 2,000 mg/kg bw administration group comprised few black erosions/ulcers in the glandular stomach and red or moderate dark red discoloration of contents of small intestine.

No macroscopic pathologic abnormalities were noted in the animals of the 500 mg/kg bw administration groups and in the surviving animal of the 2,000 mg/kg bw administration group examined at the end of the observation period.

Under the conditions of this study the median lethal dose of 3,7,1 1-trimethyldodecyn-3-ol after oral administration was found to be greater than 500 mg/kg and less than 2,000 mg/kg bw in rats.

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