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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:
3rd January 2001 to 5th March 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1'-[isopropylidenebis(p-phenyleneoxy)]bis[3-[[2-[(2-aminoethyl)amino]ethyl]amino]-2-propanol
Cas Number:
108248-15-3
Molecular formula:
C29H50N6O4
IUPAC Name:
1,1'-[isopropylidenebis(p-phenyleneoxy)]bis[3-[[2-[(2-aminoethyl)amino]ethyl]amino]-2-propanol
Constituent 2
Chemical structure
Reference substance name:
3,3'-[iminobis(ethane-2,1-diylimino)]bis{1-[4-(2-{4-[3-({2-[(2-aminoethyl)amino]ethyl}amino)-2-hydroxypropoxy]phenyl}propan-2-yl)phenoxy]propan-2-ol}
Molecular formula:
C54H87N9O8
IUPAC Name:
3,3'-[iminobis(ethane-2,1-diylimino)]bis{1-[4-(2-{4-[3-({2-[(2-aminoethyl)amino]ethyl}amino)-2-hydroxypropoxy]phenyl}propan-2-yl)phenoxy]propan-2-ol}
Constituent 3
Chemical structure
Reference substance name:
3-[4-(2-{4-[3-({2-[(2-aminoethyl)amino]ethyl}amino)-2-hydroxypropoxy]phenyl}propan-2-yl)phenoxy]propane-1,2-diol
Molecular formula:
C25H39N3O5
IUPAC Name:
3-[4-(2-{4-[3-({2-[(2-aminoethyl)amino]ethyl}amino)-2-hydroxypropoxy]phenyl}propan-2-yl)phenoxy]propane-1,2-diol
Constituent 4
Reference substance name:
Polymeric Adducts of 2,​2'-​[(1-​methylethylidene)​bis(4,​1-​phenyleneoxymethylen​e)​]​bis-oxirane and N1-​(2-​aminoethyl)​-1,​2-ethanediamine
IUPAC Name:
Polymeric Adducts of 2,​2'-​[(1-​methylethylidene)​bis(4,​1-​phenyleneoxymethylen​e)​]​bis-oxirane and N1-​(2-​aminoethyl)​-1,​2-ethanediamine
Constituent 5
Reference substance name:
Unknown components
IUPAC Name:
Unknown components
Specific details on test material used for the study:
Sponsor's identification : DETA BADGE Polymer Adduct
Description : solid block
Batch number : 18026-43-1
Date received : 23 November 2000
Storage conditions : room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female Sprague-Dawley CD (Crl: CD'" (SD) IGS BR) strain rats were supplied by
Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to
cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least
five days the animals were selected at random and given a number unique within the study by
indelible ink-marking on the tail and a number written on a cage card. At the start of the study the
males weighed 226 to 245 g, and the females 21 0 to 239 g, and were approxin~ately eight weeks
of age.
The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished
with woodflakes. With the exception of an overnight fast immediately before dosing and for
approximately three to four hours after dosing, free access to mains drinking water and food (Rat
and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was
allowed throughout the study. The diet, drinking water and bedding were routinely analysed and
were considered not to contain any contaminants that would reasonably be expected to affect the
purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25OC and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:OO
to 18:OO) and twelve hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
For the purpose of the study the test material was freshly prepared. as required, as a solution at the
appropriate concentration in distilled water.
Determination by analysis of the concentration, homogeneity and stability of the test material
preparations was not appropriate because it was not specified in the Study Plan and is not a
requirement of the Test Guideline.
Doses:
2000 mg/kg
200 mg/kg
200 mg/kg
500 mg/kg
No. of animals per sex per dose:
2000 mg/kg dose level 3 female rats
200 mg/kg dose level 3 female and 3 male rats
500 mg/kg dose level 3 female rats
Control animals:
not specified
Details on study design:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated
syringe. The volume administered to each animal was calculated according to the fasted
bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was
allowed between each sex and each dose level to confirm the survival of the previously dosed
animals.
The animals were observed for deaths or overt signs of toxicity %, 1, 2 and 4 hours after dosing
and subsequently once daily for up to fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment
or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All
animals were subjected to gross necropsy. This consisted of an external examination and opening
of the abdominal and thoracic cavities for examination of major organs. The appearance of any
macroscopic abnormalities was recorded. No tissues were retained

Results and discussion

Preliminary study:
No details specified
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No confidence levels stated.
Mortality:
All animals treated at dose levels of 2000 or 500 mglkg were found dead during the day of dosing.
There were no deaths noted at a dose level of 200 mgkg.
Clinical signs:
Signs of systemic toxicity noted at a dose level of 2000 mglkg were ataxia, pallor of the
extremities, hunched posture, lethargy, ptosis, decreased respiratory rate, laboured respiration and
loss of righting reflex. Signs of systemic toxicity noted at a dose level of 500 mglkg were
hunched posture and ataxia. There were no signs of systemic toxicity noted at a dose level of
200 mgkg
Body weight:
The surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were abnormally red lungs,
dark liver or patchy pallor of the liver, dark kidneys, haemorrhage and sloughing of the gastric
mucosa, haemorrhage andlor sloughing of the non-glandular epithelium of the stomach and
haemorrhage of the small and large intestines. A pale appearance of the kidneys was noted at
necropsy of one male treated with 200 mglkg that was killed at the end of the study. No
abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LDS0) of the test material in the Sprague-Dawley strain rat was estimated to be in the range of 200 - 500 mgikg bodyweight.
Executive summary:

The acute oral median lethal dose (LD50) of the test material in the Spra~ue-DawlevC D (Crl: CD@

JSD) IGS BR) strain rat was estimated to be in the range of 200 - 500 mgntg: bodvweight. Mortalities

were noted at dose levels of 2000 and 500 mgke bodwei~ht. No mortalities were noted in animals

treated with 200 mag: bodweight.

A group of three fasted females was treated with 2000 mgkg bodyweight. Based on the results fiom this

dose level a further group of fasted male and female animals was treated at a dose level of 200 m a g

bodyweight. At the request of the study sponsor, an additional group of three fasted females was treated

with 500 mgkg bodyweight. Dosing was performed sequentially.

The test material was administered orally as a solution in distilled water. Clinical signs and bodyweight

development were monitored during the study. All animals were subjected to gross necropsy.

All animals treated at dose levels of 2000 or 500 mgkg were found dead during the day of dosing. There

were no deaths at 200 mgkg.

Signs of systemic toxicity noted at a dose level of 2000 m a g were ataxia, pallor of the extremities,

hunched posture, lethargy, ptosis, decreased respiratory rate, labored respiration and loss of righting reflex.

Signs of systemic toxicity noted at a dose level of 500 mgkg were hunched posture and ataxia. There were

no signs of systemic toxicity noted at a dose level of 200 m a g .

The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of the animals that died during the study were abnormally red lungs, dark

liver or patchy pallor of the liver, dark kidneys, hemorrhage and epithelial sloughmg of the gastric mucosa,

hemorrhage andlor sloughmg of the non-glandular epithelium of the stomach and hemorrhage of the small

intestines. A pale appearance of the kidneys was noted at necropsy of one male treated with 200 mgkg that

was killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were

9 killed at the end of the study.