1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-(2,6,6-trimethyl-2-cyclohexen-1-yl)butan-2-one

EC Number:

250-657-4

EC Name:

4-(2,6,6-trimethyl-2-cyclohexen-1-yl)butan-2-one

Cas Number:

31499-72-6

Molecular formula:

C13H22O

IUPAC Name:

4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one

Constituent 2

Reference substance name:

1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol

EC Number:

255-256-8

EC Name:

1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol

Cas Number:

41199-19-3

Molecular formula:

C13H22O

IUPAC Name:

2,5,5-trimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-ol

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited, Margate Kent
- Age at study initiation: 5-7 weeks
- Weight at study initiation: Male: 111-128 g; Females 121-130 g
- Fasting period before study: overnight
- Housing: 5 per cage per sex in grid bottomed cages
- Diet: Pelleted diet (SQC Rat and Mouse Maintenance Diet No. 1 Expanded, produced by Special Diets Services, Witham, Essex, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 47-65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The rats were observed approximately 30 minutes, 1, 2, and 4 hours after dosing and once daily for consecutive 14 days. On the day of dosing, all animals were weighed. They were weighed again on day 8 and day 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Four hours after dosing, 2 females were found to be hypoactive and ataxic. Breathing was slow in both animals and one animal was laterally recumbent. One hour and twenty minutes later both animals were prostrate with eyes half closed, exhibiting slight piloerection, red/black bilateral
periorbital staining and were suffering tremors. At this point they were killed.

Clinical signs:

other: Clinical signs observed in the surviving animals were mild and of short duration, most animals recovering within 24 hours of dosing. The following effects were observed - Male 1: No effects - Male 2: Hypoactivity at 4 hours - Male 3: Hypoactivity at 4 hou

Gross pathology:

The necropsy findings were considered to be either due to agonal changes or to be consistent with the background macroscopic pathology of this strain of rat.
- Male 1: Enlarged submandibular lymph nodes
- Male 2: No abnormalities detected
- Male 3: Enlarged submandibular lymph nodes. Moderate pelvic dilation in the right kidney. Minimal pelvic dilation in the left kidney.
- Male 4: Enlarged submandibular lymph nodes.
- Male 5: Lungs appeared reddened and did not collapse when thorax was opened.
- Female 1: Moderately distended uterus with fluid
- Female 2: No abnormalities detected
- Female 3: Distended stomach with brown/yellow oily material. Moderately distended uterus with fluid.
- Female 4: Enlarged submandibular lymph nodes
- Female 5: Distended stomach with brown/yellow oily material.

Applicant's summary and conclusion

Interpretation of results:

other: not acute harmful

Remarks:

according to EU CLP (EC 1272/2008 and its amendments)

Conclusions:

The substance has an LD50 of >2000 mg/kg bw in a OECD TG 401 study.

Executive summary:

The acute oral toxicity has been studied in an OECD TG 401 test following GLP principles. The substance was administered at a dose of 2000 mg/kg bw to 5 male and 5 female SD rats and animals were observed for 14 days. Two females were found to be hypoactive, ataxic and suffering tremors 5.5 hours after dosing and were killed in extremis. In the surviving animals, clinical signs were limited to brown peribuccal staining in 3 animals 30 minutes after dosing and hypoactivity in all animals 4 hours after dosing. Generally recovery had occurred by day 2. There were no adverse effects an bodyweight gain in animals of either sex. There were no treatment related necropsy findings. The acute oral toxicity (LD50) was determined to be >2000 mg/kg.