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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-10-08 to 1985-10-25
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)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2,4(or 2,4,4)-trimethylhexanedinitrile
EC Number:
283-810-9
EC Name:
2,2,4(or 2,4,4)-trimethylhexanedinitrile
Cas Number:
84713-17-7
Molecular formula:
C9H14N2
IUPAC Name:
2,2,4-trimethylhexanedinitrile; 2,4,4-trimethylhexanedinitrile
Details on test material:
2,2,4(or 2,4,4)-Trimethylhexanedinitrile of Hüls AG, purity 96.5 %, main impurity 1-cyano-2-imino-3,5,5-trimethylcyclopentane = 2.42 %

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 124 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, tap water
- Acclimation period: 4 - 8 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 1 °C
- Humidity: 60 +/- 5 %
- Photoperiod: 12 hours artificial light, 12 hours dark
- Air changes: 15 per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
ADMINISTRATION: 
- Doses per time period: single dose (gavage)
- Volume administered or concentration: 0.273-0.432 ml/kg bw, undiluted  
- Post dose observation period: 14 days
Doses:
251; 283.5; 316; 398 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:
290 mg/kg bw
95% CL:
>= 254 - <= 331
Mortality:
- Number of deaths at each dose:    
251 mg/kg bw: 2 males, 0 females dead within 80 minutes   
283.5 mg/kg bw: 3 males, 2 females dead within 90 minutes   
316 mg/kg bw: 5 males, 2 females dead within 105 minutes   
398 mg/kg bw: 4 males, 4 females dead within 135 minutes
Clinical signs:
- 3 to 7 minutes after dosing: Tonic and clonic convulsions with  vocalization and marked opisthotonos and exophthalmos, salivation, bloody  
eyes and noses, lateral or prone position, heavy breathing 
- 24 hours after dosing: Surviving animals were symptom-free.
Body weight:
Body weight gain was not affected.
Gross pathology:
- animals that died during the study: Hyperemia of the small intestinal  mucosa, and hyperemia and swelling of the mucosa of the stomach
- terminal sacrifice: Only one animal showed hyperemia of the ileum. 
Other findings:
no other findings

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
harmful
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 290 mg/kg bw in rats for 2,2,4(or 2,4,4)-trimethylhexanedinitrile. Thus the substance is considered to be harmful.
Executive summary:
The test item 2,2,4(or 2,4,4)-trimethylhexanedinitrile was applied once to 4 dose-groups of rats (5 male and 5 female Wistar rats per dose-group) in doses of 251; 283.5; 316; 398 mg/kg bw as suspension in water. The observation period was 14 days. Animals died within 80 - 135 minutes after oral application of the test item. Clinical signs started 3 to 7 minutes after application and were discribed as tonic and clonic convulsions with  vocalization and marked opisthotonos and exophthalmos, salivation, bloody eyes and noses, lateral  or prone position, heavy breathing. Surviving animals were symptom-free 24 hours after dosing. Animals that died during the study showed hyperemia of the small intestinal  mucosa and hyperemia and swelling of the mucosa of the stomach. Dissection at the end of the experiment revealed only one animal with hyperemia of the ileum.  According to this study the LD50 value (oral) was determined to be 290 (254 - 331) mg/kg bw in rats for the test item 2,2,4(or 2,4,4)-trimethylhexanedinitrile.