3-cyano-3,5,5-trimethylcyclohexanone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-10-21 to 1985-11-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according 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:

3-cyano-3,5,5-trimethylcyclohexanone

EC Number:

411-490-4

EC Name:

3-cyano-3,5,5-trimethylcyclohexanone

Cas Number:

7027-11-4

Molecular formula:

C10H15NO

IUPAC Name:

3-cyano-3,5,5-trimethylcyclohexanone

Details on test material:

isophorone nitrile of Hüls AG, purity 99.3 %; impurity isophorone (78-59-1) 0.33 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Strain: Bor: WISW (SPF TNO)
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation: 5 males mean 121 g, 5 females mean 110 g
- Fasting period before study: 16 hours
- Diet: ad libitum, R10 special diet for rats, SSniff R
- Water: ad libitum, tab water
- Acclimation period: 4 - 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 °C
- Humidity (%): 60 +/- 5 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
- Air changes (per hr): 15 per hour

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: corn oil

Details on oral exposure:

ADMINISTRATION: 
- Preparation of test substance: melting at 80 °C and added to warm (50°C) corn oil
- Doses per time period: single dose (gavage)
- Volume administered or concentration: 10 ml/kg bw, 1.25-1.99 %
- Post dose observation period: 14 days

Doses:

125; 158; 199 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXAMINATIONS:
- Body weights: before, and 1, 7, 14 days post dosing
- Clinical signs and mortality: within 6 hours after dosing, thereafter  daily
- Necropsy: all animals (macroscopic)

Statistics:

LD50 is generally determined according to Litchfield and Wilcoxon, reported with 95 % confidence limits.
Means of body weights were calcultated

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

178 mg/kg bw

95% CL:

158 - 201

Remarks on result:

other: no remarks

Mortality:

MORTALITY: 
- Number of deaths at each dose:    
125 mg/kg bw: no deaths   
158 mg/kg bw: 3 males, 1 female dead within 20 hours   
199 mg/kg bw: 2 males, 4 females dead within 15 hours   

Clinical signs:

CLINICAL SIGNS: 
- 2-10 minutes after dosing: saltatory, rotatory, and extension spasms as  well as tonic spasms with vocalization (in part), distinct opisthotonos 
 and exophthalmos, salivation, bleeding eyes and nose, ruffled fur
- later: prone or lateral position, gasping breathing or increased  breathing rate, crouched posture and, from time to time, tremor
- 30-60 minutes after dosing: additionally slight sedation and ataxia in  some animals
- 4-6 hours after dosing: ruffled fur and crouched posture frome time to  time left in some animals
- 24 hours after dosing: no more signs of toxicity

Body weight:

BODY WEIGHT: Body weight gain was not affected

Gross pathology:

NECROPSY FINDINGS: 
- animals that died during the study: hyperemia of the gastric mucosa and  reddish stomach contents in some animals, light flecks on liver 
in 1  animal
- terminal sacrifice: No evidence of macroscopically discernible organ  changes 

Other findings:

no other findings

Any other information on results incl. tables

no further remarks

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: other: EU Directive 67/548/EEC

Conclusions:

According to this study the LD50 value (oral) was determined to be 178 mg/kg bw in rats for the test item isophoronnitrile.

Executive summary:

The test item Isophoronnitrile was applied once to 3 dose-groups of rats (5 male and 5 female Wistar rats per dose-group) in doses of 125, 158, 199 mg/kg bw as solution in corn oil. The observation period was 14 days. Animals died within 15 hours after oral application of the test item. Clinical signs were 2-10 minutes after dosing saltatory, rotatory, and extension spasms as  well as tonic spasms with vocalization (in part), distinct opisthotonos and exophthalmos, salivation,  bleeding eyes and nose, ruffled fur. Later they showed prone or lateral position, gasping breathing or increased  breathing rate,  crouched posture and, from time to time, tremor. After 24 hours all animals were free of signs of toxicity. Post mortem dessection revealed hyperaemia of the gastric mucosa and reddish stomach contents in some animals. Dissection at the end of the experiment revealed no evidence of mactoscopically descernible organ changes. According to this study the LD50 value (oral) was determined to be 178 mg/kg bw in rats for the test item isophoronnitrile.