Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-05-23 - 1989-06-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Limit test
Deviations:
yes
Remarks:
acclimatisation period only 4 days
Qualifier:
according to
Guideline:
other: Richtlinie 84/449/EWG (Amtsblatt der Europäischen Gemeinschaften Nr. L 251 vom 19.09.1984, S.96)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Triisopropyldiisocyanatobenzol
- Synonyms: Triisopropylbenzoldiisocyanat
- CAS name: 2,4-Diisocyanato-1,3,5-tris (1-methylethyl)-benzene
- Physical state: yellowish liquid
- Analytical purity: 98.6 %
- Boiling point: ca. 230°C
- Vapour pressure: 5 mbar at 20°C
- Storage condition of test material: room temperature, dry, storable until 31 JAN 1989

Test animals

Species:
rat
Strain:
other: Wistar (Strain Bor: WISW (SPF Cpb))
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen,
- Age at study initiation: 7 weeks (male), 10 weeks (female),
- Weight at study initiation: ca. 171 g (male), ca. 166 g (females, which were nulliparous and not pregnant),
- Fasting period before study: 16 hours before and up to 4 hours post application the animals did not receive any food (before and after this period the standard diet was given ad libitum).
- Housing: conventionally in cages equipped on low dust wood granules,
- Other: all animals in this study were housed in one room. In cases animals from other toxicological studies were housed in the same room. However appropriate organisational measures were taken to exclude confusion or any interference. The animal room was disinfected once weekly and 1 to 3 times a year a pest control was undertaken. In these occasions a contamination of the diet or any contact to the animals was excluded. The cage racks were cleaned in regular intervals and drinking bottles, lid of cages and feeding dishes were exchanged regularly. The complete cage was cleaned with hot water.
- Diet (e.g. ad libitum): "Fixed-formula"-standard diet (Altromin® 1324 Pellets (producer: Altromin GmbH und Co KG, Lage)). For feeding mangers the lids in the cage were used. The standard diet was regularly controlled and analysed for its nutritive composition and degree of contaminant with spot samples.
- Water (e.g. ad libitum): Drinking water ad libitum, the drinking bottles comprised a volume of 700 ml and were out of polycarbonate.
- Acclimation period: 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C,
- Humidity: ca. 50 ± 10%,
- Air changes: ca. 10-times air change per hour,
- Photoperiod: 12-hour light dark cycle (artificial illumination from 6 to 18 o'clock MEZ).

All animals were marked with pricrinic acid (fur, chronologically numbered), the cages were marked with: substance name, type of animal, dosing, study number, application type, sex and number of animals.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Remarks:
DAB0 - (Oleum Arachidis) Henry Lamotte, Charge 5917
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
Doses:
2000 mg/kg bw.
According to the OECD - Guideline 401 (1987), it is sufficient to characterize the acute oral toxicity with doses up to 2000 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were made twice daily (on day 0 of application observations were made several times, only daily on weekends and official holidays), the bodyweights were determined weekly
- Necropsy of survivors performed: yes (All remaining animals were sacrificed at the end of observation period after inhalation of diethylether. Every animal was submitted to a gross pathology and the findings were recorded individually.)
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
If a calculation of the mean (median) lethal dose (LD50) was possible, it was conducted via a computer assisted maximum-likelihood-method. When the results would show 0 and 100 % mortality, the geometric mean will be used as an approximate LD50 value.
If values of 0 % and 100 % of mortality appeared, the geometric mean was taken as approximate LD50.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Only one female died
Mortality:
Within the 14 day observation period, only one female animal died.
Clinical signs:
Day 0: After application of 2000 mg/kg bw all animals showed piloerection.
Day 1: the surviving animals showed collectively increased urine production.
Day 2: all surviving animals were symptom free.
In the female rat which died 3 hours after application also hypersalivation and laboured breathing was noted.
Body weight:
The body weight gain was not affected in the surviving animals (males and females).
Gross pathology:
The gross pathology investigation of the female rat (died on the day of application) revealed: hyperaemic lung and stomach.
All animals sacrificed at the end of the observation period were pathologically and anatomically normal.
Other findings:
No other findings were reported

Any other information on results incl. tables

Table 1: summary of clinical symptoms and death

Intensity and occurrence of symptoms and death
males  
Doses (mg/kg) 2000
Application volume (ml/kg) 10
Way of application PON
Number-dead animals 0
Number- animals with symptoms 5
Number- used animals 5
   
Starting time of symptoms 15'
Free of symptoms from... On 2d
Occurrence of death from ---
Occurrence of death till ---
   
  Number of animals / highest intensity
piloerection 5/2
polyuria 5/*
   
females  
Doses (mg/kg) 2000
Application volume (ml/kg) 10
Way of application PON
Number-dead animals 1
Number- animals with symptoms 5
Number- used animals 5
Starting time of symptoms 15'
Free of symptoms from... On 2d 
Occurrence of death from 3h
Occurrence of death till ---
  Number of animals / highest intensity
piloerection 5/2
hypersalivation 1/2
laboured breathing 1/1
polyuria 4/*
* observation without specifying intensity

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD TG401 with only minor deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material did not induce treatment-related mortality. The clinical signs were piloerection and increased urine production. The test material was considered to be relatively non-toxic under the conditions of the test. The LD50 was identified to be >2000 mg/kg body weight.
Executive summary:

A study on the acute oral toxicity of 2,4-Triisopropylbenzoldiisocyanat for male and female Wistar rats (Bomhard, 1990) was conducted according to the OECD Guideline 401 - standard acute method with the only deviation that the acclimatisation period was only 4 days. This deviation is not judged to influence the results of the study significantly. As dose 2000 mg/kg bw of the test substance was administered via gavage to the rats. Observations were made for a period of 14 days. No treatment-related mortalities or signs of systemic toxicity, beside piloerection during the first 24 hours following administration and an increased urine production on the following day were observed. One female rat died 3 hours after application, there as clinical signs also hypersalivation and laboured breathing were noted. No treatment-related body weight changes were reported. In the one female rat pathological abnormalities (hyperaemic lung and stomach), in all other animals, sacrificed at the end of the observation period no pathological findings were noted. The acute oral median lethal dose (LD50) of the test material in rats of both sexes observed over a period of 14 days was estimated to be greater than 2000 mg/kg bw.