4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with cyclohex-1,2-ylenediamine

Acute Toxicity: oral

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[(2-aminocyclohexyl)amino]-3-{4-[2-(4-{3-[(2-aminocyclohexyl)amino]-2-hydroxypropoxy}phenyl)propan-2-yl]phenoxy}propan-2-ol

Molecular formula:

C33H52N4O4

IUPAC Name:

1-[(2-aminocyclohexyl)amino]-3-{4-[2-(4-{3-[(2-aminocyclohexyl)amino]-2-hydroxypropoxy}phenyl)propan-2-yl]phenoxy}propan-2-ol

Constituent 2

Reference substance name:

1-[(2-aminocyclohexyl)amino]-3-(4-{2-[4-(3-{4-[2-(4-{3-[(2-aminocyclohexyl)amino]-2-hydroxypropoxy}phenyl)propan-2-yl]phenoxy}-2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)propan-2-ol

Molecular formula:

C51H72N4O7

IUPAC Name:

1-[(2-aminocyclohexyl)amino]-3-(4-{2-[4-(3-{4-[2-(4-{3-[(2-aminocyclohexyl)amino]-2-hydroxypropoxy}phenyl)propan-2-yl]phenoxy}-2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)propan-2-ol

Constituent 3

Reference substance name:

Cyclohex-1,2-ylenediamine

EC Number:

211-776-7

EC Name:

Cyclohex-1,2-ylenediamine

Cas Number:

694-83-7

Molecular formula:

C6H14N2

IUPAC Name:

cyclohexane-1,2-diamine

Constituent 4

Reference substance name:

unknown

Molecular formula:

unknown

IUPAC Name:

unknown

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Animals were received from Charles River (Stone Ridge, NY, and Raleigh, NC), on 13 Apr 2017,
09 May 2017, and 16 May 2017. Following an acclimation period of at least five days, six healthy,
non-pregnant and nulliparous female and three male Sprague Dawley rats were assigned to treatment
groups without conscious bias.
The female animals were born on 15 Feb 2017, 13 Mar 2017, and 20 Mar 2017, and the male animals were
born on 20 Mar 2017. The pretest body weight range was 310 - 327 grams for males and 185 - 216 grams
for females. The weight variation of the animals used did not exceed ±20% of the mean body weight of
the previously dosed animals within a sex.
The animals were identified by cage notation and indelible body marks, and housed in suspended wire
cages; five per sex per cage prior to dosing and three per sex per cage following dosing. Absorbent
paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat
Chow (Diet No. 5012) was freely available except for 16-20 hours prior to dosing. Water was available ad
libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a
12-hour light/dark cycle, and was kept clean and vermin free.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

ethanol

Details on oral exposure:

A single dose was administered orally by syringe and dosing needle at a dose level of 2000 mg/kg to
three female rats, at a dose level of 300 mg/kg to three female rats, and at a dose level of 1000 mg/kg to
three female rats and three male rats.

Doses:

300-1000-2000 mg/kg b.w.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Type and Frequency of Observations
In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for
toxicity and pharmacological effects and twice daily for mortality. Body weights were recorded
immediately pretest, weekly, at death and at termination in the survivors.
Post Mortem – All animals were humanely sacrificed using CO2 and were examined for gross pathology
following study termination.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female rat survived following a single 2000 mg/kg oral dose. Two female rats were found dead by Day 3 following the single 2000 mg/kg oral dose.
Three female rats and two male rats survived following a single 1000 mg/kg oral dose. One male rat was found dead by Day 2 following the single 1000 mg/kg oral dose. All three female rats survived following a single 300 mg/kg oral dose.

Clinical signs:

other: 2000 mg/kg Abnormal physical signs including piloerection, lethargy, ataxia, flaccid muscle tone, hunched posture, wetness and red staining of the nose/mouth area, diarrhea, soiling and yellow staining of the anogenital area, chromorhinorrhea, and chromod

Gross pathology:

2000 mg/kg
The gross necropsy of the decedents revealed red and brown staining of the nose/mouth area, wetness and brown and yellow staining of the anogenital area, darker than normal liver, dark areas on the kidneys, and abnormalities of the gastrointestinal tract. The gross necropsy of the surviving animal
revealed no observable abnormalities.
1000 mg/kg
The gross necropsy of the decedent revealed red staining of the nose/mouth area, soiling of the anogenital area, darker than normal lungs, and abnormalities of the gastrointestinal tract. The gross necropsy of the surviving animals revealed no observable abnormalities.
300 mg/kg
The gross necropsy revealed no observable abnormalities.

Applicant's summary and conclusion

Conclusions:

The oral LD50 of 4,4’-Isopropylidenediphenyl, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with cyclohex-1,2-ylenediamine is greater than 1000 mg/kg but less than 2000 mg/kg of body weight in rats.

Executive summary:

The oral LD50 of 4,4’-Isopropylidenediphenyl, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with cyclohex-1,2-ylenediamine is greater than 1000 mg/kg but less than 2000 mg/kg of body weight in rats.