Registration Dossier

Diss Factsheets

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:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
4,4'-Methylenediphenyl diisocyanate, oligomers, reaction products with 2-ethylhexan-1-ol
IUPAC Name:
4,4'-Methylenediphenyl diisocyanate, oligomers, reaction products with 2-ethylhexan-1-ol
Constituent 2
Reference substance name:
Desmodur MT
IUPAC Name:
Desmodur MT
Details on test material:
- Name of test material (as cited in study report): Desmodur MT
- Physical state: liquid
- Purity: 100 % (as indicated by the sponsor)
- Lot/batch No.: LL6-077
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Harlan-Winkelmann GmbH (Borchen, Germany)
- Age at study initiation: approx. 10-12 weeks
- Weight at study initiation: 176 -188 g
- Fasting period before study: 16-24 hours
- Housing: in groups
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil with the aid of 10 % acetone (dried with molecular sieve)
Details on oral exposure:
RATIONALE FOR THE SELECTION OF THE STARTING DOSE:
As described in the flow charts of Annex 2, OECD guideline 423, the starting dose level should be that which is most likely to produce mortality in
some of the dosed animals. Therefore, the limit dose 2000 mg/kg bw was chosen as starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
ADMINISTRATION
- Application volume: 10 ml/kg bw
- Post dose observation period: 14 days

EXAMINATIONS
- Clinical observations were made several times on the day of dosing and at least once a day during the 14 day observation period. Body
weights were recorded immediately prior to dosing and on days 7 and 14. Gross pathological examination was carried out on all animals.
Statistics:
none (limit test)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
other: LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All 6 animals survived the treatment.
Clinical signs:
No clinical signs were observed.
Body weight:
Body weight development was not affected.
Gross pathology:
No gross pathological findings were observed.
Other findings:
None

Any other information on results incl. tables

NOEL: 2000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category V
Remarks:
Migrated information
Executive summary:

A single oral dose of 2000 mg/kg body weight was tolerated by female rats without mortalities, clinical signs, effects on weight gain and gross pathological findings. According to OECD guideline 423 the LD50 cut-off of Desmodur MT is >= 5000 mg/kg bw. for rats (Category 5 / unclassified of the Globally Harmonized Classification System).