(4R,6R)-4-Hydroxy-2,2,6-trimethylcyclohexanone / 60046-50-6

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09/10 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The test was in accordance with the OECD Guidelines for Testing of Chemicals, No. 423, "Acute Oral Toxicity", 1996., and the Directive 96/54/EEC, B.1 tris "Acute Toxicity-Oral-Acute Toxic Class Method", 1996.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexan-1-one

EC Number:

700-052-0

Cas Number:

60046-50-6

Molecular formula:

C9H16O2

IUPAC Name:

(4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexan-1-one

Details on test material:

- Name of test material (as cited in study report): Actinol
- Physical state: solid
- Analytical purity: 99.5 %
- Lot/batch No.: 410016
- Expiration date of the lot/batch: 31 July 2000
- Stability under test conditions: stable under storage conditions, dissolved stable for 5 days at room temperature
- Storage condition of test material: room temperature, protected from sun light
- Other:

Test animals

Species:

rat

Strain:

other: HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: females 10 weeks, males 8 weeks
- Weight at study initiation:
- Fasting period before study: Overnight prior to intubation
- Housing: groups of three males or three females in Makrolon type-4 cages with standard soft bedding ("Lignocel", Schill AG, Muttenz, Switzerland)
- Diet (e.g. ad libitum): pelleted standard Kliba 3433 ad libitum, batch no. 39/99 (Provimi Kliba AG, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): community tap water from Itingen, ad libitum
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 /12


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: bi-distilled water

Details on oral exposure:

Animals received a single dose of the test article n a mg/kg body weight basis by oral gavage following fasting for approximately 16 to 16.5 hours, but with free access to water. Food was provided again approximately 3 hours after dosing. The application volume was 10 mL/kg bodyweight. Oral route was chosen as this is one possible route of human exposure during manufacture, handling and use of the test substance.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

three

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Testing animals were checked four times for mortality and viability on day 1 and once daily during days 2 to 15. Bodyweights were determined on days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Each animal was examined for changes in appearance and behaviour five times during day 1 and once daily during days 2-15. A description of all abnormalities was recorded. Necropsy was performed by experienced prosectors. At the end of the observation period on day 15, all animals were sacrificed by intraperitoneal injection of NARCOREN at a dose of at least 2.0 mL/kg bodyweight. The animals were examined macroscopically and all abnormalities recorded.

Statistics:

No statistical analysis was used as no deaths occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No death occurred during the study.

Clinical signs:

Several clinical signs like slight to marked sedation, slight to moderate ataxia, ventral position and ruffled fur were observed on test day 1 in males and females. In one female, ventral position persisted until test day 2, whereas sedation, ataxia and hunched posture persisted until test day 3. Ruffled fur was observed in one female from test day 2 until test day 4. All clinical signs were reversible on test day 5.

Body weight:

The bodyweight of the animals was within the range of commonly recorded for this strain and age (Table 1).

Gross pathology:

No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

Table 1: Bodyweights of testing animals.

Bodyweight in grams
Sex	Animal number	Day of treatment	Day 8	Day 15
Female	1	182.0	208.4	214.7
	2	181.2	194.6	208.0
	3	178.6	194.6	207.4
Male	4	210.9	250.7	280.2
	5	211.9	259.0	278.0
	6	207.4	252.3	272.2

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of Actinol after single oral administration to rats of both sexes, observed over a period of 14 days, could not be determined as no deaths occurred. LD50rat: greater than 2000 mg/kg bodyweight.

Executive summary:

A test for the acute toxicity of the testing substance Actinol was carried out in three female and three male HanIbm: WIST (SPF) rats according to OECD Guideline for the Testing of Chemicals No. 423 and Directive 96/54/EEC, Annex B.1 tris. The testing animals received one single dose of Actionl by oral gavage. The test article was suspended in vehicle (bi-distilled water) at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg. The animals were examined for clinical signs five times during day 1 and once daily during days 2 -15. Mortality/viability were recorded together with clinical signs at the same time intervals. Bodyweights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No death occurred during the study.

Several clinical signs like sedation, ventral position and ruffled fur were observed on test day 1 in males and females. All clinical signs were reversible on test day 5.

The bodyweight of the animals was within the range commonly recorded for this strain and age.

No macrocopic findings were observed at necropsy.

The median lethal dose of Actinol after a single oral dose to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occurred.

LD50 rat: greater than 2000 mg/kg bodyweigth.