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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
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions: LD50 slightly outside range of doses

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Principles of method if other than guideline:
based on FDA (1959)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of 2,2,4-trimethylhexa-1,6-diyl diisocyanate and 2,4,4-trimethylhexa-1,6-diyl diisocyanate
EC Number:
915-277-1
Cas Number:
32052-51-0
Molecular formula:
C11H18N2O2
IUPAC Name:
Reaction mass of 2,2,4-trimethylhexa-1,6-diyl diisocyanate and 2,4,4-trimethylhexa-1,6-diyl diisocyanate
Test material form:
other: liquid
Details on test material:
2,2,4(2,4,4)-trimethylhexamethylenediisocyanate of Veba-Chemie AG (now part of Evonik Industries AG), pH 5.5, no data on purity

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ORGANISMS: 
- Strain: SPF Wistar
- Source: Winkelmann, Paderborn (Germany)
- Weight at study initiation: 150-200 g
- Controls: no
Environmental conditions: - Feed: complete feed for rats (Ssniff/Intermast)
- Water: tap water ad libitum
- Room temperature: 22°C
- Humidity: 45 - 55 %

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: no vehicle
Details on oral exposure:
ADMINISTRATION: 
- Doses: 5.0; 6.3; 7.9; 10.0 ml/kg bw
- Doses per time period: single dose (gavage)
Doses:
5050; 6363; 7979; 10100 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
EXAMINATIONS:
- Post dose observation period: 14 days
- Body weights: days 0 and 14 (only surviving animals)
- Clinical signs: 20 minutes, 1, 3, 24 hours, 7 and 14 days after dosing
- Mortality: 20 minutes, 1, 3, 24 hours, thereafter daily
- Necropsy: all animals (macroscopic)
Statistics:
Litchfield and Wilcoxon (1949), J. Pharmacol. Exp. Ther. 96, 99

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 800 mg/kg bw
Mortality:
- Number of deaths at each dose:   
5050 mg/kg bw: 3 males, 3 females died on day 2   
6363 mg/kg bw: 5 males, 4 females died on days 1 (1), 2 (6), 3 (2)   
7979 mg/kg bw: 5 males, 5 females died on days 1 (5), 2 (4), 3 (1)
10100 mg/kg bw: all animals died within 24 hours except 1 male on day 2   
LD50 = 4800 (4030-5710) mg/kg bw
Clinical signs:
CLINICAL SIGNS: Beginning about 20 minutes after treatment and lasting  for approximately 24 hours: Reduced activity, asynchronism, anomalous  
positions, diarrhea, cyanosis, reduced body temperature, piloerection.
Body weight:
Body weight development of of surviving animals was normal:  
 2 males 187.5 g (day 0), 245 g (day 14)  
 3 females 163 g (day 0), 183 g (day 14)
Gross pathology:
NECROPSY FINDINGS: Post mortem sections showed redness of  gastrointestinal mucosa which were severe in animals that died during the  study and slight in surviving animals. 
Other findings:
no other findings

Any other information on results incl. tables

no further information


Applicant's summary and conclusion

Conclusions:
In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item 2,2,4(2,4,4)-trimethylhexamethylene-
diisocyanate) is 4800 mg/kg of body weight. Under the conditions of this study the acute toxicity of 2,2,4(2,4,4)-trimethylhexamethylenediisocyanate afer oral application in rats is very low.
Executive summary:

In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item 2,2,4(2,4,4)-trimethylhexamethylenediisocyanate is 4800 mg/kg of body weight. The treated animals showed signs of toxicity beginning about 20 minutes after treatment and lasting  for approximately 24 hours: Reduced activity, asynchronism, anomalous positions, diarrhea, cyanosis, reduced body temperature, piloerection during the 14 day observation period. There was no influence on the increase in body weight. Post mortem sections showed redness of  gastrointestinal mucos a which were severe  in animals that died during the study and slight in surviving animals.  Under the conditions of this study the acute toxicity of 2,2,4(2,4,4)-trimethylhexamethylenediisocyanate after oral application in rats is very low.