1,2,3,5,6,7-hexahydro-1,1,2,3,3-pentamethyl-4H-inden-4-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 April, 1985 - 29 April 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3,5,6,7-hexahydro-1,1,2,3,3-pentamethyl-4H-inden-4-one

EC Number:

251-649-3

EC Name:

1,2,3,5,6,7-hexahydro-1,1,2,3,3-pentamethyl-4H-inden-4-one

Cas Number:

33704-61-9

Molecular formula:

C14H22O

IUPAC Name:

1,1,2,3,3-pentamethyl-2,3,4,5,6,7-hexahydro-1H-inden-4-one

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 Breeding Labs, Wilmington, Massachusetts
- Weight at study initiation: 150 - 280 grams
- Fasting period before study: 18 hours
- Housing: Individually in stainless steel wire mesh cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 C +/- 3 C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h light, 12h dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.25% methylcellulose

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg

DOSAGE PREPARATION (if unusual):
Dose level 2000 mg/kg: 6.0 grams test substance in final volume of 15 ml
Dose level 3200 mg/kg: 9.6 grams test substance in final volume of 15 ml
Dose level 4000 mg/kg: dosed as received
Dose level 5000 mg/kg: dosed as received

Doses:

2000, 3200, 4000, and 5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose (10 animals per dose group)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: fourteen days
- Frequency of observations and weighing: Immediately, one and four hours after dosing, and twice daily for 14 days thereafter
- Necropsy of survivors performed: yes, gross necropsy
- Other examinations performed: clinical signs, body weight, central nervous sytem (CNS) effects, mortality, gross necropsy

Statistics:

By the method of Litchfield and Wilcoxon, JPET 966: 99-114 (1949)

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 685 mg/kg bw

Based on:

test mat.

95% CL:

> 2 043 - < 3 529

Mortality:

2000 mg/kg: 0/5 males died and 1/5 females died
3200 mg/kg: 2/5 males died and 3/5 females died
4000 mg/kg: 4/5 males died and 5/5 females died
5000 mg/kg: 5/5 males died and 5/5 females died

Mortality occured at day 1, day 2 and day 3.

Clinical signs:

other: Decreased activity, diarrhea, salivation, lacrimation, ptosis, poor grooming, piloerection, decreased or increased muscle tone, abnormal stance, abnormal gait, dyspnea, tremors, convulsions, wet pelage (ventral surface), red discoloration (ventral surface

Gross pathology:

Necropsy of animals dying on study revealed: hemorrhagic lungs, discolored and fluid-filled intestines, distended stomachs and multiple lesions in the stomachs.

Other findings:

Necropsy showed non-descended testes in one animal.
No visible lesions were observed at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: not harmful in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The substance has an LD50 of > 2685 mg/kg bw in an OECD TG 401 test

Executive summary:

In an acute oral toxicity study (OECD TG 401), four groups of ten rats (five males and five females) were administered the test substance (test article 85-206-02) at dose levels of 2000, 3200, 4000 and 5000 mg/kg bw. The rats showed decreased activity, diarrhea, salivation, lacrimation, ptosis, poor grooming, piloerection, decreased or increased muscle tone, abnormal stance, abnormal gait, dyspnea, tremors, convulsions, wet pelage (ventral surface), red discoloration, writhing and prostration. 1 of 10 rats died at 2000 mg/kg, 5 of 10 died at 3200 mg/kg, 9 of 10 died at 4000 mg/kg and 10 of 10 died at 5000 mg/kg. Necropsy of the animals dying on the study revealed hemorrhagic lungs, discolored and fluid-filled intestines, distended stomachs and multiple lesions in the stomachs. The acute oral LD50 for the test substance in male and female rats was determined to be 2901 mg/kg bw with 95% CI of 2325 - 3619 mg/kg bw. The calculated LD50 for males was 3380 mg/kg bw (95% CI: 2907 - 3930 mg/kg bw). The calculated oral LD50 for females was 2685 mg/kg bw (95% CI: 2043 - 3529 mg/kg bw).