Name: COMPLETE / SUBSTANCE : 4,4&#39;-isopropylidenediphenol, propoxylated /37353-75-6 Fri, 16 Dec 2022, 13:50:19+0900 /Legal entity owner: National Institute of Health Sciences
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iTable of Contents
0/0 ............................................................................................................................. 1
National Institute of Health Science ..................................................................... 2
4,4'-isopropylidenediphenol, propoxylated ............................................................. 3
CORE .......................................................................................................... 3
1 General information .......................................................................... 3
1.10 Assessment approach (assessment entities) ......................... 3
Assessment approach (assessment entities) ........................ 3
OECD .......................................................................................................... 4
D Health Effects .................................................................................. 4
60 Acute toxicity: oral .................................................................. 4
Acute toxicity: oral.001 ........................................................ 4
67 Repeated dose toxicity: oral .................................................... 8
Repeated dose toxicity: oral.001 ........................................... 870 Genetic toxicity in vitro ......................................................... 16
Genetic toxicity in vitro.001 ................................................ 16
Genetic toxicity in vitro.002 ................................................ 22
73 Toxicity to reproduction ........................................................ 26
Toxicity to reproduction.001 ............................................... 26
DOMAIN .................................................................................................... 35
Substance ......................................................................................... 35
Substance ................................................................................ 35
References ................................................................................................................ 36
Reference Substances ...................................................................................... 36
4,4'-isopropylidenediphenol, propoxylated ................................................... 36
Test Materials .................................................................................................. 37
4,4'-isopropylidenediphenol, propoxylated ................................................... 37
Literatures ....................................................................................................... 38
A combined repeated dose/reproductive developmental toxicity study of
4,4'-isopropylidenediphenol, propoxylated by oral administration in rats. ........ 38
In Vitro Chromosomal Aberration Test of Poly[oxy(methyl-1,2-ethanediyl)],alpha,alpha'-[(1-methylethylidene)di-4,1-phenylene]bis[omega-hydroxy- on
Cultured Chinese Hamster Cells ................................................................. 39
Reverse Mutation Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'[(1-methylethylidene)di-4,1-phenylene]bis[omega-hydroxy- on Bacteria. ......... 40
Single Dose Oral Toxicity Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1-methylethylidene)di-4, 1-phenylene]bis[omega-hydroxy- in Rats ...... 41
Legal Entities ................................................................................................... 42
National Institute of Health Sciences .......................................................... 42ii

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Dossier subject
4,4'-isopropylidenediphenol, propoxylated / 37353-75-6
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National Institute of Health Science
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LEGAL_ENTITY: National Institute of Health
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General information
Legal entity nameNational Institute of Health Science2

4,4'-isopropylidenediphenol, propoxylated
CORE
General information
Assessment approach (assessment entities)
FIXED_RECORD: Assessment approach

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OECD
Health Effects
Acute toxicity: oral
ENDPOINT_STUDY_RECORD: Acute toxicity: oral.001

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Administrative data
Endpoint
acute toxicity: oral
Type of information
experimental study
Adequacy of study
key study
Robust study summary
true
Used for classification
false
Used for SDS
false
Reliability
1 (reliable without restriction)
Rationale for reliability incl. deficiencies
guideline study
Reliability 1

Data source
Reference
Single Dose Oral Toxicity Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha, alpha'-[(1-methylethylide /MHLW (Ministry of Health, Labour and Welfare), Japan / study report
Data accessdata published

Materials and methods
4Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance
yes
Test type
acute toxic class method
Limit test
yes

Test material
Test material information
4,4'-isopropylidenediphenol, propoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-isopropylidenediphenol, propoxylated- Lot No.: L3-6S005-A (Sanyo Chemical Industries, Ltd.)- Purity: >99%
- Solubility: insoluble in water- Physical state: Colorless liquid- Storage condition of test material: in cool (2-6 ℃) and dark place

Test animals
Speciesratcommon species
Strain
Crj: CD(SD)rat
Sex
femaleDetails on test animals or test system and environmental conditions
TEST ANIMALS- Source: Charles River Japan Inc.
- Age at the time of purchase: 9 weeks old- Weight at dosing: 229-246 g– Used animal number: A total of 12 females (3 animals/step)- Housing: Three animal/cage- Diet (e.g. ad libitum): Ad libitum- Water (e.g. ad libitum): Ad libitum- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS- Temperature (°C): 22±3
- Humidity (%): 55±105- Ventilation (per hr): >10 times- Photoperiod (hrs light / hrs dark): 12/12

Administration / exposure
Route of administration
oral: gavage
Vehiclewater
Details on oral exposure
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg b.w.
Doses
2000 mg/kg bw (1st and 2nd steps)
No. of animals per sex per dose
3 females/doseControl animals
noDetails on study design- Duration of observation period following administration: 14 days
- Frequency of observations: for one hour after dosing, and 2 h, 4h, and 6 h after dosing. Twice a dayon the next day of dosing. Thereafter once a day.
- Frequency of weighing: Days 1 (before administration), 4, 8 and 15- Necropsy of survivors performed: Yes
Statistics
Not used

Results and discussion
Effect levels
Key result
true
Sex
female
Dose descriptor
LD50
Effect level>2000

mg/kg bw

Based onact. ingr.
Mortality
No deaths were observed in the first and second dosing groups.
Clinical signs
other:
6

Salivation in 1 animal (1st dosing) and restlessness in 3 and 2 animals (1st and 2nd dosing) wereobserved immediately after dosing but recovered within 30 min. Decreased locomotor activity wasobserved in all animals and diarrhea in 4 animals from 1 hour after administration, and decreased
locomotor activity was observed even at 6 hours after administration. Soiled fur was observed fromthe day after administration to up to 5 days.
Gross pathology
There were no changes related to the test substance.

Applicant's summary and conclusion
Conclusions
The acute oral LD50 of 4,4'-isopropylidenediphenol, propoxylated was >2000 mg/kg bw in female rats
based on the study conducted according to the OECD TG 423 .

7

Repeated dose toxicity: oral
ENDPOINT_STUDY_RECORD: Repeated dose toxicity: oral.001

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Author:Date: 2022-12-16T13:18:52.498+09:00
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Administrative data
Endpoint
repeated dose toxicity: oral, otherType of information
experimental study
Adequacy of study
key study
Robust study summary
false
Used for classification
false
Used for SDS
false
Reliability
1 (reliable without restriction)
Rationale for reliability incl. deficiencies
guideline study
Reliability 1
Cross-reference
Reason / purpose for cross-reference
reference to same study
Related information
OECD / Toxicity to reproduction / Toxicity to reproduction.001 / 4,4&#39;-isopropylidenediphenol,
propoxylated / 37353-75-6

Data source
Reference
A combined repeated dose/reproductive developmental toxicity study of 4,4'-isopropylidenediphenol,p / Ministry of Health, Labor and Welfare, Japan / study report
Data accessdata published

Materials and methods
8Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction /Developmental Toxicity Screening Test)
Deviationsno
GLP compliance
yes
Limit test
no

Test material
Test material information
4,4'-isopropylidenediphenol, propoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-isopropylidenediphenol, propoxylated- Analytical purity: > 99%- Storage condition of test material: at a cold (temperature 2-6 °C) and dark place, with airtightstopper.
- Stability under test conditions: The stability of test material was identified by analysis of the remainder.

Test animals
Speciesratcommon rodent species
Strainother: Crl:CD(SD)Sexmale/female
Details on test animals or test system and environmental conditions
TEST ANIMALS- Source: Charles River Japan, Inc., Tsukuba Breeding Center.
- Age at study initiation: 10 weeks old- Weight at study initiation: male 361 g (329-385 g), female 228 g (199-253 g)- Housing: Animals were individually housed in bracket-type metallic wire-mesh cages (265W × 426D ×200H mm), Dams were bred individually or with individual littermates in polycarbonate cages with flat
floors (265W x 426D x 200H mm) and standard bedding.
- Diet: Solid feed (MR stock: Nosan Corporation) was given ad libitum.
- Water: Tap water was given ad libitum.
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 22±3 (actual temperature: 22.2-25.0 °C)- Humidity (%): 55±10% (actual humidity: 45-58%)- Air changes (per hr): >10- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light (light: 7:00~19:00)

9Administration / exposure
Route of administration
oral: gavage
Vehicleolive oil
Details on oral exposure- Amount of vehicle (if gavage): 5 mL/kg- Dosing volume: 5 mL/kg
Analytical verification of doses or concentrations
yes
Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating(P)Females: 42-53 days including 14 days pre-mating, mating and gestation periods and the days
until day 4 of lactation
Female (no mating, satellite group): 42 days
Frequency of treatment
Once/day, 7 days/week
Doses / concentrations
Dose / conc.
0mg/kg bw/day (actual dose received)

Dose / conc.
30

mg/kg bw/day (actual dose received)

Dose / conc.
120

mg/kg bw/day (actual dose received)

Dose / conc.
500

mg/kg bw/day (actual dose received)

No. of animals per sex per dose
Main group:12 animals/sex/dose
Satellite (Recovery) group: 5 males/dose and 5 females/dose (0 and 500 mg/kg bw/day)Control animals
yes, concurrent vehicle
Details on study design- Dose selection rationale: Based on the results of a 14-day preliminary study, the highest dose of 500
mg/kg bw/day was selected as an expected obvious toxic dose, and the lowest dose of 30 mg/kg
bw/day was selected as an expected no toxic dose. The middle dose levels of 120 mg/kg bw/day
were selected.
10

- Rationale for animal assignment (if not random): Body weight-balanced randomization[14-day preliminary study]
A 14-day repeated dose oral toxicity test (Crl:CD(SD) rats, doses: 0 (olive oil), 50, 100, 200, 500 or
1000 mg/kg bw/day). At 100 mg/kg bw/day or more, Salivation, tendency of suppress weight gain, hi
gh value trend of total cholesterol were observed. At 500 mg/kg bw/day or more, High value of liver
and adrenal gland weight, total protein, albumin, and calcium, and reduced prothrombin time wereobserved. At 1000 mg/kg bw/day, changes of general condition, obvious suppression of weight gain,
death of one male and two females were observed.

Examinations
Observations and examinations performed and frequency
CAGE SIDE OBSERVATIONS: Yes- Time schedule: 3 times/day (am: before and after administration; pm) during the administration
period. 2 times/day (am and pm) during the recovery period.
DETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: Once before the start of administration, and once every week by the end of the study
period.
BODY WEIGHT: Yes- Time schedule for examinations:
Males were weighed on Day 1, 7, 14, 21, 28, 35, and 42 of administration, and weighed on Day 7 and
14 of recovery.
Female satellite groups were weighted same frequencies to male recovery groups.
Females in the main groups were weighed on Day 1, 7 and 14 of administration and copulated
females were weighed on Day 0, 7, 14 and 20 of gestation, and days 0 and 4 of lactation.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption: Yes
Measurement of food consumption was conducted on all animals at the following frequencies:
Males in the main and recovery groups; on Day 1, 7, 14, 21, 28, 35, and 41 of administration, and on
Day 7 and 13 of recovery.
Female satellite groups were weighted same frequencies to male recovery groups.
Females in the main group; on Day 1, 7 and 14 of administration and copulated females were weighedon Day 0, 7, 14 and 20 of gestation, and days 0 and 3 of lactation.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes- Time schedule for collection of blood: At the end of administration period, or at the end of recovery
period in both sexes- Anaesthetic used for blood collection: ether- Animals fasted: Yes- How many animals: 5 animals/sex/group- Parameters examined included RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelet, ret
iculocyte, PT, APTT, WBC and differential WBC.
CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: At the end of administration period, or at the end of recovery
period in both sexes- Animals fasted: Yes- How many animals: 5 animals/sex/group- Parameters examined included total protein, albumin, A/G ratio, total bilirubin, glucose, total cho
lesterol, triglyceride, phospholipid, AST, ALT, LDH, ChE, ALP, gamma-GTP, BUN, creatinine, Na, K, Cl,
Ca and IP.
11

URINALYSIS OF MALES: Yes- Time schedule for collection of urine (male only): On Day 37 of administration, and on Day 9 of recovery.
- Metabolism cages used for collection of urine: Yes- How many animals: 5 animals/group- Parameters examined included color, cloudy, urine volume, specific gravity, pH, protein, glucose, ketone body, bilirubin, occult blood and urobilinogen.
NEUROBEHAVIOURAL EXAMINATION: Yes- Time schedule for examinations: On week 6 of the administration period, and on week 2 of therecovery period- Dose groups that were examined: All dose groups (5 animals/sex/group)- Battery of functions tested: sensory activity (hearing reaction, eye sight reaction, sense of touch
reaction, pain reaction, pupil reflex, righting reflex), grip strength, motor activity
Sacrifice and pathology
GROSS PATHOLOGY: Yes
ORGAN WEIBHT: Yes [brain, thymus, heart, liver, kidney, adrenal gland, spleen, seminal vesicle, testis,
epididymis, pituitary, thyroid]
HISTOPATHOLOGY: Yes, [brain, pituitary, spinal cord, thyroid, parathyroid, heart, thymus, trachea, lung, liver, kidney, adrenal, spleen, stomach, small intestine, large intestine, sciatic nerve, bone, bonemarrow, lymph nodes (mesenteric and cervical lymph nodes), urinary bladder, testis, seminal vesicle,
prostate, epididymis, mammary gland, ovary, uterus and gross abnormalities site.]
Statistics
As for parametric data (grip strength, locomotor activity, body weight, body weight gain, food consu
mption, hematology and clinical chemistry data, organ weights, quantitative urinalysis data, numberof corpora lutea, number of implantation sites, number of pups born, number of pups alive, number ofstillborn), the values of means and standard deviations were calculated per group. When more than
three groups exist in the test group, Bartlett test for variance was done, and if the variance was ho
mogenous, ANOVA was applied. If the variance was not homogenous or data was non-parametric(differential WBC percentage, qualitative urinalysis data, stages of spermatogenesis, length of the
estrous cycle, implantation index, delivery index, live birth index, viability index,), Kruskal-Wallis rank s
um test was used. Consequently, if the result was significant, Dunnett multiple comparison or Dunnett typed method was used for detection of statistical significance against control group. When the nu
mber of the test group was two, F-test was used as for parametric data.
Then, student's t-test or Aspin-Welch's t-test was applied depending on the result of homogeneity ofvariance. While, as for non-parametric data, Man-Whitney's U-test was applied. Furthermore, as fo
r categorized data (incidence of abnormal findings in clinical observation, detailed observation, sensory functional examination, necropsy and histopathology, copulation index, fertility index, gestationindex), Fischer's exact test was used. In any tests, level of significance was set at 5%.

Results and discussion
Results of examinations
Clinical signs
effects observed, treatment-related
Description (incidence and severity)[treatment-related effect]:
Slight ptosis was observed in two males at 500 mg/kg bw/day. Moderate decrease in locomotor
activity and emaciation were observed in one male at 500 mg/kg bw/day.
12

Slight emaciation was observed in one female at 500 mg/kg bw/day.
[non-treatment-related]:
Salivation was observed in eleven males and eleven females at 120 mg/kg bw/day, in all males andfemales at 500 mg/kg bw/day. This finding was considered to be repelling reaction to administration
liquid and not to be related to toxicity of the test substance.
Mortality
mortality observed, treatment-related
Description (incidence)
One female died at 500 mg/kg bw/day on gestation day 22.
Body weight and weight changes
effects observed, treatment-related
Description (incidence and severity)
Depression of body weight gains were observed in males at 500 mg/kg bw/day.
Food consumption and compound intake (if feeding study)
effects observed, non-treatment-related
Description (incidence and severity)
Increased food consumption was observed in males at 500 mg/kg bw/day and in females at 120 mg/
kg bw/day on Day 14 of administration only. These variation were without dose-related trends. Th
erefore, these variation were considered to be incidental and not to be related to treatment of the test
substance.
Food efficiency
not examined
Water consumption and compound intake (if drinking water study)
not examined
Ophthalmological findings
not examined
Haematological findings
effects observed, non-treatment-related
Description (incidence and severity)
Decreased MCH and PT were observed in male at 500 mg/kg bw/day. At decreased MCH, however,this variation was within ranges of historical control data, and erythrocyte count and hemoglobin concentration showed no changes. Therefore, this variation was considered to be incidental and not
to be related to treatment of the test substance. At decreased PT, however, this variation was not ext
ensible and was not seen in females. Therefore this variation was toxicologically meaningless change.
At the end of recovery period, decreased neutrophil ratio in differentiation of leukocyte was observedin males at 500 mg/kg bw/day and decreased APTT was observed in females at 500 mg/kg bw/day.
However, these variation was within ranges of historical control data, and were not present at the endof the administration period. Therefore, these variation were considered to be incidental and not to berelated to treatment of the test substance.
Clinical biochemistry findings
effects observed, treatment-related
Description (incidence and severity)
Decreased total protein was observed in males at 120 and 500 mg/kg bw/day. Decreased albumin
was observed in males at 500 mg/kg bw/day and increased total cholesterol was observed in both sexes at 500 mg/kg bw/day.
13

Urinalysis findings
effects observed, non-treatment-related
Description (incidence and severity)
At the end of recovery period, decreased K value was observed in females at 500 mg/kg bw/day.
This value was within range of historical control data. Therefore, this variation was considered to beincidental and not to be related to treatment of the test substance.
Behaviour (functional findings)
no effects observed
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Description (incidence and severity)[treatment-related effect]:
At the end of administration period, increases in absolute and relative liver weights were observed inmales at 500 mg/kg bw/day and increases in relative liver weight was observed in females at 500
mg/kg bw/day.
[non-treatment-related]:
Increases in relative kidney weight and relative brain weight were observed in males at 500 mg/kg
bw/day. However, these changes were considered due to the reduction in terminal body weights.
Therefore these changes were no toxicological meaning.
Gross pathological findings
effects observed, treatment-related
Description (incidence and severity)
Slight enlargement of liver was observed in both sexes at 500 mg/kg bw/day.
Histopathological findings: non-neoplastic
effects observed, treatment-related
Description (incidence and severity)
Liver: Slight hypertrophy of centrilobular hepatocyte was observed in four males and five females at
500 mg/kg bw/day.
Small intestine: Dilatation of lacteal was observed in two males and one female at 120 mg/kg bw/
day, and five males and five females at 500 mg/kg bw/day.
Histopathological findings: neoplastic
not examined

Effect levels
Key result
true
Dose descriptor
NOAEL
Effect level30

mg/kg bw/day (actual dose received)

Based ontest mat.
14

Sex
male/female
Basis for effect level
clinical biochemistry
Decreased total protein was observed in males at 120 and 500 mg/kg bw/day.
histopathology: non-neoplastic
Small intestine: Dilatation of lacteal was observed in two males and one female at 120 mg/kg bw/
day, and five males and five females at 500 mg/kg bw/day.

Any other information on results incl. tables
Figures and Tables (in English) are available in the following full report of the study.
http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF37353-75-6d.pdf

Applicant's summary and conclusion
Executive summary
In the combined repeated dose and reproductive/developmental screening test, SD rats were treatedorally with the test substance at the doses of 0, 30, 120 and 500 mg/kg bw/day, Males were dosed for
42 days including 14-days pre-mating and mating periods. Females were dosed during the periods ofpre-mating, mating, gestation and days until day 4 of lactation. As a result, decreased total protein wasobserved in males at 120 and 500 mg/kg bw/day. Dilatation of lacteal on small intestine was observed in
two males and one female at 120 mg/kg bw/day, and five males and five females at 500 mg/kg bw/day.
On the basis of these effects, NOAEL for repeated-dose toxicity was determined to be 30 mg/kg bw/
day in male and female rats.

15

Genetic toxicity in vitro
ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.001

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Author:Date: 2022-12-16T13:21:44.575+09:00
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Administrative data
Endpoint
in vitro gene mutation study in bacteria
Type of information
experimental study
Adequacy of study
key study
Robust study summary
true
Used for classification
false
Used for SDS
false
Reliability
1 (reliable without restriction)
Rationale for reliability incl. deficiencies
guideline study
Reliability 1

Data source
Reference
Reverse Mutation Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1-methylethylidene)di-4,1- /MHLW (Ministry of Health, Labour and Welfare), Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
16Guideline
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
in vitro gene mutation study in bacteria
Qualifieraccording to guideline
Guideline
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
genetic toxicity in vitro, other
GLP compliance
yesType of assay
bacterial reverse mutation assay
in vitro gene mutation study in bacteria

Test material
Test material information
4,4'-isopropylidenediphenol, propoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-isopropylidenediphenol, propoxylated or Bis
phenol A-PO
- Lot No.: L3-6S005-A (Sanyo Chemical Industries, Ltd.)- Purity: >99%
- Solubility: insoluble in water- Physical state: Colorless liquid- Storage condition of test material: in cool (2-6 ℃) and dark place

MethodSpecies / strain
Species / strain / cell typeS. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2bacteria
Metabolic activation
with and without
Metabolic activation system
S9 mix; SD male rat liver, induced by phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose
Preliminary test+/- S9 mix: 0, 20, 50, 100, 200, 500, 1000, 2000, 5000 μg/plate
Main test+/- S9 mix:0, 156, 313, 625, 1250, 2500, 5000 μg/plate
Vehicle / solvent
DMSO
17

Controls
Untreated negative controls
yes
Negative solvent / vehicle controls
yes
Positive control substance
9-aminoacridine
9-aminoacridine hydrochloride (-S9 mix: TA1537)
sodium azide(-S9 mix: TA1535)
other: -S9 mix: 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA 100, TA98 and WP2 uvrA/pKM101), +S9
mix: 2-aminoanthracene (all strains)
Details on test system and experimental conditions
METHOD OF APPLICATION: Preincubation
DURATION- Preincubation period: 20 min at 37°C
- Exposure duration:48 hrs
NUMBER OF PLATES: 3
NUMBER OF REPLICATIONS: 2
DETERMINATION OF CYTOTOXICITY- Method: other: growth inhibition
Evaluation criteria
A chemical was judged to be mutagenic when the mean number of revertant colonies per plateincreased more than twice that of the negative control and when the dose-related and reproducible increase was observed.
Statistics
Not used

Results and discussion
Test results
Key result
false
Species / strain
S. typhimurium TA 1535
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Untreated negative controls validity
valid
18

Positive controls validity
valid
Key result
false
Species / strain
S. typhimurium TA 1537
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Untreated negative controls validity
valid
Positive controls validity
valid
Key result
false
Species / strain
S. typhimurium TA 98
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Untreated negative controls validity
valid
Positive controls validity
valid
Key result
false
Species / strain
S. typhimurium TA 100
bacteria
19

Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Untreated negative controls validity
valid
Positive controls validity
valid
Key result
false
Species / strain
E. coli WP2 uvr A pKM 101
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Untreated negative controls validity
valid
Positive controls validityvalid

Any other information on results incl. tables
Figures and Tables (in Japanese) are available in the following full report of the study.http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF37353-75-6e.pdf
Tables (in English) are attachted to this document. Please download the export file to see the Tables.

Applicant's summary and conclusion
Conclusions
Interpretation of results' negative
Executive summary20

In a bacterial reverse mutation assay using Salmonella typhimurium TA100, TA1535, TA98, and TA1537,
and Escherichia coli WP2uvrA/pKM101 (OECD TG 471), 4,4'-isopropylidenediphenol, propoxylated was
negative with or without metabolic activation.

21

ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.002

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Dossier UUID:
Author:Date: 2022-12-16T13:22:50.229+09:00
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Administrative data
Endpoint
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information
experimental study
Adequacy of study
key study
Robust study summary
true
Used for classification
false
Used for SDS
false
Reliability
1 (reliable without restriction)
Rationale for reliability incl. deficiencies
guideline study
Reliability 1

Data source
Reference
In Vitro Chromosomal Aberration Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1-methyleth /MHLW (Ministry of Health, Labour and Welfare), Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)in vitro cytogenicity / chromosome aberration study in mammalian cells

22Qualifieraccording to guideline
Guideline
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
genetic toxicity in vitro, other
GLP compliance
yesType of assay
in vitro mammalian chromosome aberration testin vitro cytogenicity / chromosome aberration study in mammalian cells

Test material
Test material information
4,4'-isopropylidenediphenol, propoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-isopropylidenediphenol, propoxylated or Bis
phenol A-PO
- Lot No.: L3-6S005-A (Sanyo Chemical Industries, Ltd.)- Purity: >99%
- Solubility: insoluble in water- Physical state: Colorless liquid- Storage condition of test material: in cool (2-6 ℃) and dark place

MethodSpecies / strain
Species / strain / cell typeother: Chinese hamster lung(CHL/IU) cells
Metabolic activation
with and without
Metabolic activation system
S9 mix; SD male rat liver, induced by phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose
Cell growth inhibition study
short-term treatment (-S9 mix): 0, 46.88, 93.75, 187.5, 375, 750, 1500, 3000 μg/mL
short-term treatment (+S9 mix): 0, 46.88, 93.75, 187.5, 375, 750, 1500, 3000 μg/mL
continuous treatment (24 hrs and 48 hrs): 0, 46.88, 93.75, 187.5, 375, 750, 1500, 3000 μg/mL
Main study
short-term treatment-S9: 0, 12.5, 25, 50, 75, 100 μg/mL+S9: 0, 25, 50, 100, 150, 200 μg/mL+S9: 0, 100, 125, 150 μg/mL (confirmation test)
Contentious treatment-S9: 0, 6.25, 12.5, 25, 50, 100 μg/mL-S9: 0, 50, 60, 75, 100 μg/mL (confirmation test)

23

Vehicle / solvent
DMSO
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
Positive controls
yes
Positive control substancebenzo(a)pyrene+S9 mix
mitomycin C-S9 mix
Details on test system and experimental conditions
METHOD OF APPLICATION: Exposure duration:short-term treatment:6 hrs + 18 hr
contentious treatment: 24 hrs
SPINDLE INHIBITOR: Colcemid
STAIN: Giemsa stain for 20 min.
NUMBER OF REPLICATIONS: 3
NUMBER OF CELLS EVALUATED: 200 cells /concentration (100 cells/plate x 2)
DETERMINATION OF CYTOTOXICITY- Method: relative total growth
Evaluation criteria
For the evaluation of the frequencies of structural aberrations and of polyploidy induced, statisticalanalysis was employed. When significant deference (<5%) was obtained by the multiple chi-square
test, Fisher’s exact test was employed to compare the vehicle control group and each concentrationgroup. When frequencies of chromosomal aberrations were significantly increased in >=2 conce
ntration groups, and when concentration dependent increase was observed, it was judged to be positive.

Results and discussion
Test results
Key result
false
Species / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
with
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity (at 75 and 100 μg/mL)24

Vehicle controls validity
valid
Positive controls validity
valid
Key result
false
Species / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity (short-term treatment: at 150 and 200 μg/mL, contentious treatment: at 60, 75, 100 ug/
mL)
Vehicle controls validity
valid
Positive controls validityvalid

Any other information on results incl. tables
Figures and Tables (in Japanese) are available in the following full report of the study.
http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF37353-75-6f.pdf
Tables (in English) are attachted to this document. Please download the export file to see the Tables.

Applicant's summary and conclusion
Conclusions
Interpretation of results: negative with and without metabolic activation
Executive summary
The in vitro chromosomal aberration test using CHL/IU cells (OECD TG 473) was negative with andwithout metabolic activation.

25

Toxicity to reproduction
ENDPOINT_STUDY_RECORD: Toxicity to reproduction.001

UUID: 5205a094-5fbf-456c-86b0-764132010499
Dossier UUID:
Author:Date: 2022-12-16T13:25:32.894+09:00
Remarks:

Administrative data
Endpoint
reproductive toxicity, other A combined repeated dose/reproductive developmental toxicity study
Type of information
experimental study
Adequacy of study
key study
Robust study summary
false
Used for classification
false
Used for SDS
false
Reliability
1 (reliable without restriction)
Rationale for reliability incl. deficiencies
guideline study
Reliability 1
Cross-reference
Reason / purpose for cross-reference
reference to same study
Related information
OECD / Repeated dose toxicity: oral / Repeated dose toxicity: oral.001 / 4,4&#39;isopropylidenediphenol, propoxylated / 37353-75-6

Data source
Reference
A combined repeated dose/reproductive developmental toxicity study of 4,4'-isopropylidenediphenol,p / Ministry of Health, Labor and Welfare, Japan / study report
Data accessdata published26

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction /Developmental Toxicity Screening Test)
Deviationsno
GLP compliance
yes
Limit test
no

Test material
Test material information
4,4'-isopropylidenediphenol, propoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-isopropylidenediphenol, propoxylated- Analytical purity: > 99%- Storage condition of test material: at a cold (temperature 2-6 °C) and dark place, with airtightstopper.
- Stability under test conditions: The stability of test material was identified by analysis of the remainder.

Test animals
Speciesrat
Strainother: Crl:CD(SD)Sexmale/female
Details on test animals or test system and environmental conditions
TEST ANIMALS- Source: Charles River Japan, Inc., Tsukuba Breeding Center.
- Age at study initiation: 10 weeks old- Weight at study initiation: male 361 g (329-385 g), female 228 g (199-253 g)- Housing: Animals were housed individually, bracket-type metallic wire-mesh cages (265W × 426D ×200H mm) , Dams were bred individually or with individual littermates in polycarbonate cages withflat floors (265W x 426D x 200H mm) and standard bedding.
- Diet: Solid feed (MR stock: Nosan Corporation) was given ad libitum.
- Water: Tap water was given ad libitum.
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 22±3 (actual temperature: 22.2-25.0 °C)
27

- Humidity (%): 55±10% (actual humidity: 45-58%)- Air changes (per hr): >10- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light (light: 7:00~19:00)

Administration / exposure
Route of administration
oral: gavage
Vehicleolive oil
Details on exposure- Amount of vehicle (if gavage): 5 mL/kg- Dosing volume: 5 mL/kg
Analytical verification of doses or concentrations
yes
Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating (P)Females: 42-53 days including 14 days p
remating, mating and gestation periods and the days until day 4 of lactation
Female (no mating, satellite group): 42 days
Frequency of treatment
Once/day, 7 days/week
Doses / concentrations
Dose / conc.
0mg/kg bw/day (actual dose received)

Dose / conc.
30

mg/kg bw/day (actual dose received)

Dose / conc.
120

mg/kg bw/day (actual dose received)

Dose / conc.
500

mg/kg bw/day (actual dose received)

No. of animals per sex per dose
Main group:12 animals/sex/dose
Satellite (Recovery) group: 5 males/dose and 5 females/dose (0 and 300 mg/kg bw/day)28

Control animals
yes, concurrent vehicle
Details on study design- Dose selection rationale: Based on the results of a 14-day preliminary study, the highest dose of 500
mg/kg bw/day was selected as an expected obvious toxic dose, and the lowest dose of 30 mg/kg
bw/day was selected as an expected no toxic dose. The middle dose levels of 120 mg/kg bw/day
were selected.
- Rationale for animal assignment (if not random): Body weight-balanced randomization[14-day preliminary study]
A 14-day repeated dose oral toxicity test (Crl:CD(SD) rats, doses: 0 (olive oil), 50, 100, 200, 500 or
1000 mg/kg bw/day). At 100 mg/kg bw/day or more, Salivation, tendency of suppress weight gain, hi
gh value trend of total cholesterol were observed. At 500 mg/kg bw/day or more, High value of liver
and adrenal gland weight, total protein, albumin, and calcium, and reduced prothrombin time wereobserved. At 1000 mg/kg bw/day, changes of general condition, obvious suppression of weight gain,
death of one male and two females were observed.

Examinations
Parental animals: Observations and examinations
CAGE SIDE OBSERVATIONS: Yes- Time schedule: 3 times/day (am: before and after administration; pm) during the administration
period. 2 rimes/day (am and pm) during the recovery period.
DETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: Once before the start of administration, and once every week by the end of the study
period.
BODY WEIGHT: Yes- Time schedule for examinations:
Males were weighed on Day 1, 7, 14, 21, 28, 35, and 42 of administration, and weighed on Day 7 and
14 of recovery.
Female satellite groups were weighted same frequencies to male recovery groups.
Females in the main groups were weighed on Day 1, 7 and 14 of administration and copulated
females were weighed on Day 0, 7, 14 and 20 of gestation, and days 0 and 4 of lactation.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption: Yes
Measurement of food consumption was conducted on all animals at the following frequencies:
Males in the main and recovery groups; on Day 1, 7, 14, 21, 28, 35, and 41 of administration, and on
Day 7 and 13 of recovery.
Female satellite groups were weighted same frequencies to male recovery groups.
Females in the main group; on Day 1, 7 and 14 of administration and copulated females were weighedon Day 0, 7, 14 and 20 of gestation, and days 0 and 3 of lactation.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes- Time schedule for collection of blood: At the end of administration period, or at the end of recovery
period in both sexes- Anaesthetic used for blood collection: ether- Animals fasted: Yes- How many animals: 5 animals/sex/group- Parameters examined included RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelet, ret
iculocyte, PT, APTT, WBC and differential WBC.
29

CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: At the end of administration period, or at the end of recovery
period in both sexes- Animals fasted: Yes- How many animals: 5 animals/sex/group- Parameters examined included total protein, albumin, A/G ratio, total bilirubin, glucose, total cho
lesterol, triglyceride, phospholipid, AST, ALT, LDH, ChE, ALP, gamma-GTP, BUN, creatinine, Na, K, Cl,
Ca and IP.
URINALYSIS OF MALES: Yes- Time schedule for collection of urine (male only): On Day 37 of administration, and on Day 9 of recovery.
- Metabolism cages used for collection of urine: Yes- How many animals: 5 animals/group- Parameters examined included color, cloudy, urine volume, specific gravity, pH, protein, glucose, ketone body, bilirubin, occult blood and urobilinogen.
NEUROBEHAVIOURAL EXAMINATION: Yes- Time schedule for examinations: On week 6 of the administration period, and on week 2 of therecovery period- Dose groups that were examined: All dose groups (5 animals/sex/group)- Battery of functions tested: sensory activity (hearing reaction, eye sight reaction, sense of touch
reaction, pain reaction, pupil reflex, righting reflex), grip strength, motor activity
Oestrous cyclicity (parental animals)
Vaginal smears were collected from all females in the main groups and microscopically examined
every day from the day after
the start of administration until the day copulation was confirmed.
Sperm parameters (parental animals)
Parameters examined in all P male parental generations: testis weight, epididymis weight, histopatho
logical examinations for testes, epididymides, seminal vesicle including coagulating gland and ventral
prostate.
Litter observations
PARAMETERS EXAMINED: The following parameters were examined in F1 offspring: number and sexof pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physicalor behavioral abnormalities.
Postmortem examinations (parental animals)
METHOD OF SACRIFICED: All animals were sacrificed by exsanguination under ether anesthesia.
SACRIFICE: Male animals: On Day 42, Maternal animals: on Day 5 of lactation, and Male recovery andfemale satellite animals: on next Day 14 of recovery.
GROSS PATHOLOGY: Yes
ORGAN WEIBHT: Yes [brain, thymus, heart, liver, kidney, adrenal gland, spleen, seminal vesicle, testis,
epididymis, pituitary, thyroid]
HISTOPATHOLOGY: Yes, [brain, pituitary, spinal cord, thyroid, parathyroid, heart, thymus, trachea,
lung, liver, kidney, adrenal, spleen, stomach, small intestine, large intestine, sciatic nerve, bone, bonemarrow, lymph nodes (mesenteric and cervical lymph nodes), urinary bladder, testis, seminal vesicle,
prostate, epididymis, mammary gland, ovary, uterus and gross abnormalities site.]
Postmortem examinations (offspring)
SACRIFICE- The F1 offspring were sacrificed at 4 days of age.
30

GROSS NECROPSY- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, andabdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGTHS- Not examined.
Statistics
As for parametric data (grip strength, locomotor activity, body weight, body weight gain, food consu
mption, hematology and clinical chemistry data, organ weights, quantitative urinalysis data, numberof corpora lutea, number of implantation sites, number of pups born, number of pups alive, number ofstillborn), the values of means and standard deviations were calculated per group. When more than
three groups exist in the test group, Bartlett test for variance was done, and if the variance was ho
mogenous, ANOVA was applied. If the variance was not homogenous or data was non-parametric(differential WBC percentage, qualitative urinalysis data, stages of spermatogenesis, length of the
estrous cycle, implantation index, delivery index, live birth index, viability index,), Kruskal-Wallis rank s
um test was used. Consequently, if the result was significant, Dunnett multiple comparison or Dunnett typed method was used for detection of statistical significance against control group. When the nu
mber of the test group was two, F-test was used as for parametric data.
Then, student's t-test or Aspin-Welch's t-test was applied depending on the result of homogeneity ofvariance. While, as for non-parametric data, Man-Whitney's U-test was applied. Furthermore, as fo
r categorized data (incidence of abnormal findings in clinical observation, detailed observation, sensory functional examination, necropsy and histopathology, copulation index, fertility index, gestationindex), Fischer's exact test was used. In any tests, level of significance was set at 5%.
Reproductive indices
Estrous cycle: Mean days from metaeatrus I (III) to next III.
Copulation index (%) = (No. of pairs with successful copulation/No. of pairs mated) × 100
Fertility index (%) = (No. of pregnant females/No. of pairs with successful copulation) × 100
Gestation index (%) = (No. of females with live pups/No. of pregnant females) × 100
Implantation index (%) = (No. of implantation sites/No. of corpora lutea) × 100
Delivery index (%) = (No. of pups born/No. of implantation sites) × 100
Live birth index (%) = (No. of live pups on day 0/No. of pups born) × 100
Sex ratio =Total number of male pups/Total number of female pups
Offspring viability indices
Viability index (%) = (No. of live pups on day 4/No. of live pups on day 0) × 100

Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
Clinical signs
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Mortality
mortality observed, treatment-related
Description (incidence)See 7.5.1 Repeated dose toxicity: oral.001
Body weight and weight changes
effects observed, treatment-related31Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Food consumption and compound intake (if feeding study)
effects observed, non-treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Food efficiency
not examined
Water consumption and compound intake (if drinking water study)
not examined
Ophthalmological findings
not examined
Haematological findings
effects observed, non-treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Clinical biochemistry findings
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Urinalysis findings
effects observed, non-treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Behaviour (functional findings)
no effects observed
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Immunological findings
not examined
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Gross pathological findings
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Neuropathological findings
not examined
Histopathological findings: non-neoplastic
effects observed, treatment-related
32

Description (incidence and severity)
See 7.5.1 Repeated dose toxicity: oral.001
Histopathological findings: neoplastic
not examined

Reproductive function / performance (P0)
Reproductive function: oestrous cycle
effects observed, treatment-related
Description (incidence and severity)
Disorder of estrous cycle was observed in five females at 500 mg/kg bw/day.
Reproductive function: sperm measureseffects observed, non-treatment-related
Description (incidence and severity)
Increase the number of spermatogonia in seminiferous epithelia at Stage XII in males at 500 mg/kg b
w /day. However, test substance related histopathological changes were not observed in testis. Therefore, these variation were considered to be incidental and not to be related to treatment of the test
substance.
Reproductive performanceno effects observed

Effect levels (P0)
Key result
true
Dose descriptor
NOAEL
Effect level120

mg/kg bw/day (actual dose received)

Based ontest mat.
Sexmale/female
Basis for effect level
reproductive function (oestrous cycle)
Disorder of estrous cycle was observed in five females at 500 mg/kg bw/day.

Results: F1 generation
General toxicity (F1)Clinical signs
no effects observed
Mortality / viability
no mortality observed
33

Body weight and weight changes
effects observed, treatment-related
Description (incidence and severity)
Decrease of body weight in offsprings at 500 mg/kg bw/day.
Sexual maturation
no effects observed
Gross pathological findings
no effects observed

Effect levels (F1)
Key result
true
Dose descriptor
NOAEL
Generation
F1
Effect level120

mg/kg bw/day (actual dose received)

Based ontest mat.
Sexmale/female
Basis for effect level
body weight and weight gain
Decrease of body weight in offsprings at 500 mg/kg bw/day.

Any other information on results incl. tables
Figures and Tables (in English) are available in the following full report of the study.
http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF37353-75-6d.pdf

Applicant's summary and conclusion
Executive summary
In the combined repeated dose and reproductive/developmental screening test, SD rats were treatedorally with the test substance at the doses of 0, 30, 120 and 500 mg/kg bw/day, Males were dosed for
42 days including 14-days pre-mating and mating periods. Females were dosed during the periods ofpre-mating, mating, gestation and days until day 4 of lactation. As a result, decrease of body weight
in offsprings at 500 mg/kg bw/day. Disorder of estrous cycle was observed in five females at 500
mg/kg bw/day. On the basis of these effects, NOAEL for reproductive and developmental toxicity wasdetermined to be 120 mg/kg bw/day in parental animals and F1 offspring.

34

DOMAIN
Substance
SUBSTANCE: 4,4'-isopropylidenediphenol, propoxylated
UUID: 8e317b70-f413-4fe3-ae86-c2452462eff0
Dossier UUID:
Author:Date: 2022-12-16T13:49:52.558+09:00
Remarks:
Substance name
4,4'-isopropylidenediphenol, propoxylated
Other substance identifiers
Identifiercommon nameIdentity
propoxylated bisphenol A
Legal entity
National Institute of Health Sciences / Kawasaki / Japan

Identification of substance
Reference substance
4,4'-isopropylidenediphenol, propoxylated / 37353-75-6
EC number

EC name

CAS number

CAS name

37353-75-6

Poly[oxy(methyl-1,2-ethanediyl)],alpha,
methylethylidene)di-4, 1-phenylene]bis[omega-hydroxy-

IUPAC nameRole in the supply chain
Manufacturer
false
Importer
false
Only representativefalse
Downstream user
false

35

alpha'-[(1-References
Reference Substances
REFERENCE_SUBSTANCE: 4,4'-isopropylidenediphenol,
propoxylated
UUID: 837cba43-f251-440d-9b53-5dad38755d76
Dossier UUID:
Author:Date: 2022-12-16T13:15:57.211+09:00
Remarks:
Reference substance name
4,4'-isopropylidenediphenol, propoxylated

Inventory
CAS number
37353-75-6
CAS name
Poly[oxy(methyl-1,2-ethanediyl)], alpha, alpha'-[(1-methylethylidene)di-4, 1-phenylene]bis[omega-hyd
roxy-

Synonyms
Synonyms
Identifiercommon nameIdentity
propoxylated bisphenol A

Molecular and structural information
Structural formula

Remarks
n=a: 0.0%, n=2: 5.7%, n=3: 11.4%, n=4: 22.1%, n=5: 24.9%, n=6: 18.1%, n=7: 10.2%, n>=8: 7.6%

36

Test Materials
TEST_MATERIAL_INFORMATION: 4,4'isopropylidenediphenol, propoxylated
UUID: d1071874-285f-4e11-a1ef-104305f8c05b
Dossier UUID:
Author:Date: 2022-12-16T13:13:10.739+09:00
Remarks:Name
4,4'-isopropylidenediphenol, propoxylated

37

Literatures
LITERATURE: A combined repeated dose/
reproductive developmental toxicity study of 4,4'isopropylidenediphenol, propoxylated by oral
administration in rats.
UUID: 09124065-e91d-43d9-b827-dde035e817a6
Dossier UUID:
Author:Date: 2018-03-23T10:30:59.000+09:00
Remarks:

General information
Reference Typestudy report
Title
A combined repeated dose/reproductive developmental toxicity study of 4,4'-isopropylidenediphenol,
propoxylated by oral administration in rats.
Author
Ministry of Health, Labor and Welfare, Japan
Testing facility
Research institute for animal science in biochemistry and toxicology (RIAS)
Study number
06-11938

LITERATURE: In Vitro Chromosomal Aberration Testof Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1methylethylidene)di-4,1-phenylene]bis[omega-hydroxyon Cultured Chinese Hamster Cells
UUID: 22376bec-6ca3-41c1-be78-2055d7a999e2
Dossier UUID:
Author:Date: 2018-08-27T11:19:37.000+09:00
Remarks:

General information
Reference Typestudy report
Title
In Vitro Chromosomal Aberration Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1-methyleth
ylidene)di-4,1-phenylene]bis[omega-hydroxy- on Cultured Chinese Hamster Cells
AuthorMHLW (Ministry of Health, Labour and Welfare), Japan
Year
2010
Bibliographic source
Japan Existing Chemical Data Base (JECDB) http://dra4.nihs.go.jp/ mhlw_data/jsp/SearchPageENG.jsp
Testing facility
Research Institute for Animal Science in Biochemistry and Toxicology
Report number
06-11739

LITERATURE: Reverse Mutation Test of
Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1methylethylidene)di-4,1-phenylene]bis[omega-hydroxyon Bacteria.
UUID: bc242e28-071f-4dd3-86ef-4d2a968eb55a
Dossier UUID:
Author:Date: 2018-08-27T11:18:57.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Reverse Mutation Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha,alpha'-[(1-methylethylidene)di-4,1phenylene]bis[omega-hydroxy- on Bacteria.
AuthorMHLW (Ministry of Health, Labour and Welfare), Japan
Year
2010
Bibliographic source
Japan Existing Chemical Data Base (JECDB) http://dra4.nihs.go.jp/mhlw_data/jsp/SearchPage
ENG.jsp
Testing facility
Research Institute for Animal Science in Biochemistry and Toxicology
Report number
06-11640

LITERATURE: Single Dose Oral Toxicity Test of
Poly[oxy(methyl-1,2-ethanediyl)], alpha, alpha'-[(1methylethylidene)di-4, 1-phenylene]bis[omega-hydroxyin RatsUUID: ad2bcf2a-f8b2-4095-ae57-0ca84ab65616
Dossier UUID:
Author:Date: 2018-08-27T11:17:48.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Single Dose Oral Toxicity Test of Poly[oxy(methyl-1,2-ethanediyl)], alpha, alpha'-[(1-methylethylidene)di-4, 1-phenylene]bis[omega-hydroxy- in Rats
AuthorMHLW (Ministry of Health, Labour and Welfare), Japan
Year
2010
Bibliographic source
Japan Existing Chemical Data Base (JECDB) http://dra4.nihs.go.jp/ mhlw_data/jsp/SearchPage
ENG.jsp
Testing facility
Research Institute for Animal Science in Biochemistry and Toxicology
Report number
06-11841

Legal Entities
LEGAL_ENTITY: National Institute of Health Sciences
UUID: IUC4-b036ff75-0f3c-323b-b200-ed5f46cf5101
Dossier UUID:
Author:Date: 2022-11-07T15:49:29.000+09:00
Remarks:

General information
Legal entity nameNational Institute of Health Sciences
Remarks
Disclaimer: The contents in this document were created based on the MHLW (Ministry of Health,Labour and Welfare) peer reviewed study reports (in Japanese) in JECDB (Japan Existing Chemical
Database) at http://dra4.nihs.go.jp/mhlw_data/jsp/SearchPageENG.jsp. Authorship is in the Divisionof Risk Assessment, the National Institute of Health Sciences, and the contents do not reflect any official MHLW opinions or any other regulatory policies.

Address
Address 1
Tonomachi 3-25-26
Address 2
Kawasaki-ku
Postal code
210-9501
Town
KawasakiRegion / State
Kanagawa
CountryJapan
JP

Identifiers
Other IT system identifiers
IT system
LEO
ID
10767
IT systemIUCLID442

ID
16558402024DIV750

43