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Toxicological information

Acute Toxicity: oral

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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:
comparable to 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)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,2,3,3,6-hexamethylindan-5-yl methyl ketone
EC Number:
239-360-0
EC Name:
1,1,2,3,3,6-hexamethylindan-5-yl methyl ketone
Cas Number:
15323-35-0
Molecular formula:
C17H24O
IUPAC Name:
1-(1,1,2,3,3,6-hexamethyl-2,3-dihydro-1H-inden-5-yl)ethan-1-one
Test material form:
solid
Specific details on test material used for the study:
- Description: White waxy solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, the Netherlands
- Weight at study initiation: Males: 260-284g; Females: 154-184g
- Fasting period before study: In the overnight period before treatment till 4 hours after treatment
- Housing: Groups of 5 per sex in stainless steel cages with wire-screen bottom and front
- Diet: The Institute's cereal-based open formula diet for rats and mice, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 40-60
- Air changes (per hr): about 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: isopropyl myristate
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 17.5% (w/v)

DOSE VOLUME APPLIED: 4, 4.8, 5.76, 6.91, 8.29 mL/kg bw for the dose groups 700, 840, 1008, 1209, 1451 mg/kg bw, respectively
Doses:
700, 840, 1008, 1209, 1451 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed for signs of toxicity during the first 4 post-treatment hours and thereafter at least once daily. Individual body weights of the rats were recorded on day 0, 7, and 14.
- Necropsy of survivors performed: yes
Statistics:
LD50 was calculated according to the method of Weil, C.W. (Biometrics 8 (1952) 249-263)

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
797 mg/kg bw
Based on:
test mat.
95% CL:
>= 703 - <= 905
Mortality:
700 mg/kg bw: Males 1/5; Females 2/5
840 mg/kg bw: Males 2/5; Females 5/5
1008 mg/kg bw: Males 2/5; Females 5/5
1209 mg/kg bw: Males 3/5; Females 5/5
1451 mg/kg bw: Males 4/5; Females 5/5
Deaths occurred between 18 hours and 9 days after dosing.
Clinical signs:
Within a few hours after dosing the rats showed sluggishness and piloerection. Later on, haematuria was observed until 2 days after treatment. After a few days, moreover, encrustations around eyes and nostrils, and signs of emaciation were observed. These latter phenomena persisted in all surviving rats the first post-treatment week. In the second post-treatment week the survivors recovered gradually and looked quite healthy again at the end of the observation period.
Body weight:
The individual body weight of the survivors on day 7, revealed growth retardation or weight loss in all survivors. On day 14 the body weight of most of the rats in the higher dose groups were still lower or only slightly higher than the initial weight.
Gross pathology:
Macroscopic examination at autopsy of the rats that died on the first few post-treatment days revealed blood-stained urine in the bladder of all rats. In the rats that died thereafter and in those that survived the observation period no treatment-related gross alterations were found.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria