Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-05-20 to 2009-07-02
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes
Test type:
up-and-down procedure

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-Methylenediphenyl diisocyanate, oligomers
EC Number:
500-040-3
EC Name:
4,4'-Methylenediphenyl diisocyanate, oligomers
Cas Number:
25686-28-6
Molecular formula:
C14 H10 N O [C29 H20 N4 O2]n NCO nmean = typical 0.04 – 0.23
IUPAC Name:
4,4'-Methylenediphenyl diisocyanate, oligomers

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: propylene carbonate - NF
Details on oral exposure:
The 175 mg/kg dose level was prepared at 35 mg/ml and dosed at 5 ml/kg
(dose volume). The 550, 2000 and 5000 mg/kg levels were dosed as received at 0.45, 1.6 or 4.1 ml/kg, respectively. The 175 mg of test article
was brought to a volume of 5 ml with the vehicle. Each preparation was
made daily on the day of dosing. The stock bottle was inverted several
times prior to dispensing. The 175 mg/kg formulation was described as a
clear liquid. The test article stock bottle was purged with nitrogen after use.
Doses:
The test article/dosing suspensions were
administered on Day 1 to each rat as a single
dose via oral gavage. Animals were fasted
overnight prior to dose administration. Each
animal received its designated dose based on
fasted body weight determined just prior to dosing.
The dose volumes were between 0.45 and 5 ml/kg
and were based on the specific density of
1.22 g/ml as per the MSDS.
Details on study design:
The first animal was dosed at an initial dose level of 175 mg/kg. Since this
animal survived, the second animal received a higher dose (550 mg/kg) and the
third received the test article at 2000 mg/kg. One animal followed by two
additional animals were dosed at 5000 mg/kg. The dose for each successive
animal was adjusted up or down, depending on the previous result. The test
continued based on the fixed time interval outcomes of all the animals up to that
point and until one of the stopping criteria was first met. There were three
possible stopping criteria.
• 3 consecutive animals survive at the limit dose;
• 5 reversals occur in any 6 consecutive animals test;
• or at least 4 animals have followed the first reversal and the specific likelihood-ratios exceed the critical value.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was not observed in any of the animals dosed at 175, 550, 2000 or
5000 mg/kg of the test article.
Clinical signs:
All animals appeared normal throughout the study at 550, 2000, 5000 mg/kg.
Clinical signs of soft stool and piloerection were observed in one animal at
175 mg/kg on Day 2.
Body weight:
No biologically significant effect was seen on body weights of animals on Days 8
and 15.
Gross pathology:
Terminal necropsy revealed no visible lesions in any of the animals at 175, 550
2000 or 5000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the oral LDso for the test material in rats was estimated to be greater than 5000 mg/kg.