[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

EC Number:

275-156-8

EC Name:

[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Cas Number:

71048-82-3

Molecular formula:

C13H20O

IUPAC Name:

[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Test material form:

liquid

Test animals

Species:

mouse

Strain:

other: BLU: Ha (ICR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Blue Spruce Farms, Inc., Altamont, NY
- Weight at study initiation: between 15 - 36 grams
- Fasting period before study: The animals were fasted overnight (approximately 18 hours) prior to dosing
- Housing: plastic cages with wood shavings as bedding, in groups of five
- Diet: Charles River pelleted RMH 3000 supplied ad libitum after dosing
- Water: supplied ad libitum after dosing
- Acclimation period: at least three days prior to test initiation

ENVIRONMENTAL CONDITIONS
- Temperature: 70 ± 3°F

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test material was administered as a corn oil solution at varying concentrations, at a constant volume of 20 mL/kg.

Doses:

940, 1346, 1475, 1600, 1902, 2025, 2150, 2225, 2350, and 2692 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Animals were observed for 14 days following administration of the test material. Toxic effects and mortality were recorded throughout the duration of the test period.

Statistics:

First the LD50 was calculated by the methos of Knudsen and Curtis; only three to four dose levels were used and the resulting 95% confidence intervals appeared to be smaller than felt the data warranted. Recalculation was done by Finney Probit analysis (December 7, 1979). However, results obtained by the Finney analysis appeared incorrect (e.g. calculated LD50 greater than highest dose tested while 90% mortality occurred below the highest dose). Therefore, the final calculations were made using the Litchfield-Wilcoxon method.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 400 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 085 - <= 1 806

Remarks on result:

other: based on a calculation with the Litchfield-Wilcoxon method.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 850 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% CL cannot be calculate from this data; based on a calculation with the Litchfield-Wilcoxon method.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 625 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 332 - <= 1 990

Remarks on result:

other: based on a calculation with the Litchfield-Wilcoxon method.

Mortality:

Male;
940 mg/kg bw: 2/5 animals
1346 mg/kg bw: 0/5 animals
1475 mg/kg bw: 2/5 animals
1600 mg/kg bw: 4/5 animals
1902 mg/kg bw: 4/5 animals
2025 mg/kg bw: 4/5 animals
2150 mg/kg bw: 4/5 animals
2225 mg/kg bw: 3/5 animals
2350 mg/kg bw: 4/5 animals
2692 mg/kg bw: 4/5 animals

Female;
940 mg/kg bw: 0/5 animals
1346 mg/kg bw: 0/5 animals
1475 mg/kg bw: 1/5 animals
1600 mg/kg bw :4/5 animals
1902 mg/kg bw: 5/5 animals
2025 mg/kg bw: 5/5 animals
2150 mg/kg bw: 4/5 animals
2225 mg/kg bw: 3/5 animals
2350 mg/kg bw: 5/5 animals
2692 mg/kg bw: 5/5 animals

Clinical signs:

other: - Males: All animals at all doses showed decrease of activity. Ataxia at all dose levels, not with all animals. Salivation at dose 1600 with 3 animals. Urinary incontinence at all doses (except 1475 and 2692), not all animals. Tremors at all doses >16

Gross pathology:

Summary of Necropsy Findings (Combined Data Males and Females):
Dose 940 mg/kg bw: Intestines: vascularized.
Dose 1346 mg/kg bw: No deaths.
Dose 1475 mg/kg bw: Lungs: dark. Liver: pale. Spleen: pale, pale and granular; appears large. Kidneys: pale. G.I. Tract: filled with brown fluid. Intestines: white. Stomach: fluid filled.
Dose 1600 mg/kg bw: Lungs: pale. Liver: pale. Kidneys: pale. Spleen: dark. G.I. Tract: containing yellow like substance. Stomach: full.
Dose 1902 mg/kg bw: Lungs: dark. Liver: pale. Kidneys: pale and mottled. Spleen: dark.
Dose 2025 mg/kg bw: Lungs: dark. Liver: pale. Kidneys: pale and mottled. Spleen: pale.
Dose 2150 mg/kg bw: Lungs: pinkish gray. Liver: pale. Kidney: pale and mottled. Spleen: dark.

Applicant's summary and conclusion

Interpretation of results:

other: Harmful

Remarks:

In accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The acute oral LD50 for the substance in male and female mice was determined to be between 300 and 2000 mg/kg bw (1400 mg/kg bw). Based on this result, the test material shall be classified for acute oral toxicity and is acute toxic 4, using the phrase: Harmful if swallowed.

Executive summary:

The oral acute toxicity of the test substance was evaluated in mice, performed similar to OECD Guideline 401, predating GLP. Five albino mice per sex per dose were administered the substance orally as a corn oil solution at a constant volume of 20 mL/kg bw at the following concentrations: 940, 1346, 1475, 1600, 1902, 2025, 2150, 2225, 2350, 2692 mg/kg bw. Animals were observed for 14 days following administration of the test material. Toxic effects and mortality were recorded throughout the duration of the test period.

Clinical signs included: decrease of activity, ataxia, salivation, urinary incontinence, tremors. Mortality was observed at all dose levels (except at 1346 mg/kg bw). Macroscopic changes were evident in the lungs, spleen, kidneys, G.I. tract and stomach.

The LD50's for males, females and the two sexes combined were calculated using the Litchfield-Wilcoxon method: males 1400 mg/kg bw; females 1850 mg/kg bw; combined 1625 mg/kg bw.