Name: COMPLETE / SUBSTANCE : 4,4&#39;-Isopropylidenediphenol, ethoxylated /32492-61-8 Fri, 16 Dec 2022, 13:07:30+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, ethoxylated ............................................................... 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 .................................................... 7
Repeated dose toxicity: oral.001 ........................................... 770 Genetic toxicity in vitro ......................................................... 15
Genetic toxicity in vitro.001 ................................................ 15
Genetic toxicity in vitro.002 ................................................ 20
73 Toxicity to reproduction ........................................................ 24
Toxicity to reproduction.001 ............................................... 24
DOMAIN .................................................................................................... 33
Substance ......................................................................................... 33
Substance ................................................................................ 33
References ................................................................................................................ 35
Reference Substances ...................................................................................... 35
4,4'-Isopropylidenediphenol, ethoxylated ..................................................... 35
Test Materials .................................................................................................. 36
4,4'-Isopropylidenediphenol, ethoxylated ..................................................... 36
Literatures ....................................................................................................... 37
A combined repeated dose/reproductive developmental toxicity study of
4,4'-Isopropylidenediphenol, ethoxylated by oral administration in rats. .......... 37
In Vitro Chromosomal Aberration Test of poly(oxy-1,2ethanediyl),alpha,alpha'- [(1-methylethylidene)di-4,1-phenylene]bis[omegahydroxy- on Cultured Chinese Hamster Cells ............................................... 38
Reverse Mutation Test of poly(oxy-1,2-ethanediyl),alpha,alpha'- [(1methylethylidene)di-4,1-phenylene]bis[omega-hydroxy- ................................. 39
Legal Entities ................................................................................................... 40
National Institute of Health Sciences .......................................................... 40ii

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4,4'-Isopropylidenediphenol, ethoxylated / 32492-61-8
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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, ethoxylated
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
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

Materials and methods
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
4Test material information
4,4'-Isopropylidenediphenol, ethoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-Isopropylidenediphenol, ethoxylated- Lot No.: L3-6S004-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
femaleAdministration / 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 2h, 4h, and 6h 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 discussion5Effect levels
Sexfemale
Dose descriptor
approximate LD50
Effect level5000

mg/kg bw

Mortality
No mortality observed.
Clinical signs
other:
Restlessness and decreased locomotor activity were observed on on the day of administration.
Soiled fur was observed the day after administration.
Body weight
other body weight observations No effects observed/
Gross pathology
No abnormarities were observed.

6

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

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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,
ethoxylated / 32492-61-8

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

Materials and methods
7

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, ethoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-Isopropylidenediphenol, ethoxylated- Analytical purity: > 99%- Storage condition of test material: at a cold (temperature 2-6°C) and dark place, with airtight stopper.
- 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., Atsugi Breeding Center.
- Age at study initiation: 10 weeks old- Weight at study initiation: male 361 g (334-396 g), female 235 g (216-260 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: 22.1-25.0°C)- Humidity (%): 55±10% (actual humidity: 46-60%)- Air changes (per hr): >108

- 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 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: 42-47 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)

Dose / conc.
1000

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 1000 mg/kg bw/day)9

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 of1000 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 and 500 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 500 mg/kg bw/day or more, salivation, low value trend of urinary ketone
bodies, high value trend of total cholesterol and liver weight were observed. At 1000 mg/kg bw/day,high value trend of blood calcium, and reduced prothrombin time 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
10

- 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
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, bone marrow, lymph nodes (mesenteric and cervical lymph nodes), urinary bladder, testis, seminal vesicle, prostate, epididymis, mammary gland, ovary and uterus.]

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
11

Results of examinations
Clinical signs
effects observed, non-treatment-related
Description (incidence and severity)
Transient salivation was observed in all males and females at 500 and 1000 mg/kg bw/day.
Mortality
no mortality observed
Body weight and weight changes
effects observed, treatment-related
Food consumption and compound intake (if feeding study)no effects observed
Food efficiency
not examined
Water consumption and compound intake (if drinking water study)
not examined
Ophthalmological findings
not examined
Haematological findings
effects observed, treatment-related
Clinical biochemistry findings
effects observed, treatment-related
Urinalysis findings
no effects observed
Behaviour (functional findings)
no effects observed
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Gross pathological findings
no effects observed
Histopathological findings: non-neoplastic
effects observed, treatment-related
Histopathological findings: neoplastic
not examined
Details on results
CLINICAL SIGNS AND MORTALITY:
Mortality: There was no death.
Clinical signs: Transient salivation was observed in all males and females at 500 and 1000 mg/kg bw/
day.
DETAILED CLINICAL OBSERVATIONS, MANIPULATIVE TEST, GRIP STRENGTH TEST AND LOCOMOTOR ACTIVITY MEASUREMENT: There were no changes related to the test substance.
BODY WEIGHT:
12

[At the dosing period]
Depression of body weight gains were observed in males at 1000 mg/kg bw/day.
[At the recovery period]
There were no changes related to the test substance in any groups.
FOOD CONSUMPTION: There were no changes related to the test substance in any groups at the dosing and recovery periods.
HAEMATOLOGY:[At the end of dosing period]: Decrease in RBC, hemoglobin concentration and hematocrit value, andincreases in reticulocyte count were observed in females at 1000 mg/kg bw/day.
[At the end of recovery period]: There were no changes related to the test substance in any groups.
CLINICAL CHEMISTRY:[At the end of dosing period]: Increases in total cholesterol and Ca were observed in males at 500 mg/
kg bw/day. Increase in total cholesterol were observed in males and females at 1000 mg/kg bw/day.
Increase in ALT and Ca were observed in females at 1000 mg/kg bw/day.
[At the end of recovery period]: There were no changes related to the test substance in any groups.
URINALYSES OF MALES: There were no changes related to the test substance in any groups at thedosing and recovery periods.
ORGAN WEIGHTS:[At the end of dosing period]
Increase in absolute and relative liver weights were observed in females at 500 and 1000 mg/kg bw/
day. Increase in relative liver weights were observed in males at 500 and 1000 mg/kg bw/day groups.
Increase in absolute and relative kidney weights were observed in males at 500 mg/kg bw/day. Increase in relative kidney weights were observed in males at 1000 mg/kg bw/day.
[At the end of recovery period]: There were no changes related to the test substance in any groups.
GROSS PATHOLOGY: There were no changes related to the test substance in any groups at the end of
dosing and recovery periods.
HISTOPATHOLOGY: NON-NEOPLASTIC:[At the end of dosing period]
Liver: Slightly centrilobular hypertrophy hepatocyte was observed in two males and three females at
500 mg/kg bw/day and three males and five females at 1000 mg/kg bw/day.
Kidney: Moderately basophilic change in the proximal tubule was observed in one male at 500 mg/kg
bw/day and two males at 1000 mg/kg bw/day.
[At the end of recovery period]: There were no changes related to the test substance in any groups.

Effect levels
Key result
true
Dose descriptor
NOAEL
Effect level120

mg/kg bw/day (actual dose received)
13Based on
test mat.
Sexmale/female
Basis for effect level
histopathology: non-neoplastic
Liver: Centrilobular hypertrophy hepatocyte was observed in males and females at 500 mg/kg bw/
day or more.
organ weights and organ / body weight ratios
Increase in liver weight was observed in males and 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/PDF32492-61-8d.pdf

Applicant's summary and conclusion
Executive summary
A combined repeated-dose toxicity study with a reproduction/developmental toxicity screening test
was performed in accordance with OECD TG422. Male and female rats (12 animals/sex/dose) wereadministered 4,4'-isopropylidenediphenol, ethoxylated at 0 (vehicle: olive oil), 30, 120, 500, and 1000 mg/
kg bw/day. Including a 14-day pre-mating period and a subsequent mating period, males were dosed
for 42 days. Females were dosed for 42–47 days, including 14-day premating, mating, and gestation
periods, until lactation day 4. Of the 12 males dosed at 0 and 1000 mg/kg bw/day, 5 were treated as arecovery group. Five additional females receiving 0 and 1000 mg/kg bw/day were treated as a satellitegroup. These females were dosed with 4,4'-isopropylidenediphenol, ethoxylated for 42 days, without
mating, and examined after a 14-day recovery.
Decreased body weight was observed in males in the 1000 mg/kg bw/day group. Decreases in RBC,
hemoglobin and hematocrit and increases in the reticulocyte of females in the 1000 mg/kg bw/day
group were observed toward the end of the administration period. The total cholesterol and Ca levels
were increased in males receiving 500 and 1000 mg/kg bw/day and in females at 1000 mg/kg bw/
day. Increases in ALT were observed in females at 1000 mg/kg bw/day. In both sexes, the absolute
and/or relative liver weights were increased at 500 mg/kg bw/day and greater. Relative kidney weight
were also greater in males at 500 mg/kg bw/day and greater. Histopathological analysis also revealeda hypertrophy of centrilobular hepatocytes for both sexes as well as a basophilic tubule of the kidneyin males at 500 and 1000 mg/kg bw/day. Such changes were no longer observed after the recovery
period. Judging from the effects on the liver and kidney of the 4,4'-Isopropylidenediphenol, ethoxylated
at 500 mg/kg bw/day, it was concluded that the NOAEL for the repeated-dose toxicity in rats was 120
mg/kg bw/day.

14

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

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Author:Date: 2022-12-16T11:47:55.137+09:00
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Administrative data
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-1,2-ethanediyl),alpha,alpha'- [(1-methylethylidene)di-4,1-phenylen /Ministry of Health, Labour and Welfare (MHLW), Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
in vitro gene mutation study in bacteria
GLP complianceyes
15Type of assay
bacterial reverse mutation assay
in vitro gene mutation study in bacteria

Test material
Test material information
4,4'-Isopropylidenediphenol, ethoxylated

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: Rat liver, induced with phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose
Dosage of each strain with or without S9 mix-S9 mix: 0, 62.5, 125, 250, 500, 1000 and 2000 μg /plate (TA strains) and 156, 313, 625, 1250, 2500,
and 5000 μg/plate (E. coli WP2)
+S9 mix: 0, 156, 313, 625, 1250, 2500, 5000 μg /plate (All strains)
Maximum concentration was established based on the result of the preliminary test at concentration
up to 5000 ug/plate. In this test, the growth inhibition was observed at 2000 μg/plate and higher forS. typhimurium TA100, TA1535, TA98 and TA1537 without S9 mix.
Vehicle / solvent
DMSO
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substance
9-aminoacridine
without S9 mix (TA1537)
sodium azide
without S9 mix (TA1535)
other: 2-(2-Furyl)-3-(5-nitro -2-furyl)acrylamide (without S9 mix TA100, TA98, WP2uvrA), 2-Aminoa
nthracene (with S9 mix all strains)
Details on test system and experimental conditions
METHOD OF APPLICATION: Preincubation
16

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
cytotoxicity at 1000 μg/plate (-S9mix), 2500 and 5000 μg/plate (+S9 mix)
Vehicle controls validity
valid
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
cytotoxicity at 2000 μg/plate (-S9 mix), 2500 and 5000 μg/plate (+S9 mix)
Vehicle controls validity
valid
17

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
cytotoxicity at 2000 μg/plate (-S9 mix), 2500 and 5000 μg/plate (+S9 mix)
Vehicle controls validity
valid
Positive controls validity
valid
Key result
false
Species / strain
S. typhimurium TA 100
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity at 2000 μg/plate (-S9 mix), 2500 and 5000 μg/plate (+S9 mix)
Vehicle 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
negative18

Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Positive controls validity
valid
Additional information on results
There were no precipitation in any test concentration.

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/PDF32492-61-8e.pdf
Tables (in English) are attachted to this document. Please download the export file to see the Tables.

Overall remarks, attachments
Attachments
Remarks
Tables for Ames test

Applicant's summary and conclusion
Conclusions
In a bacterial reverse mutation assay using S. typhimurium TA100, TA1535, TA98, and TA1537, andE. coli WP2uvrA/pKM101 (OECD TG 471), negative results were obtained for 4,4'-isopropylidenedi
phenol, ethoxylated with or without metabolic activation.

19

ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.002

UUID: bd9559d0-e698-4b78-a7f3-891552987e48
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Author:Date: 2022-12-16T11:47:38.574+09:00
Remarks:

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-1,2-ethanediyl),alpha,alpha'- [(1-methylethylidene) /MHLW, 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

20

Qualifieraccording to guideline
Guideline
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
genetic toxicity in vitro, other
GLP compliance
yes

Test material
Test material information
4,4'-Isopropylidenediphenol, ethoxylated
Specific details on test material used for the study- Lot No.: L3-6S004-A (Sanyo Chemical Industries, Ltd.)- Purity: >99%
- Solubility: insoluble in water- Physical state: Colorless liquid- Storage condition of test material: in cool (2-6 degree C) and dark place

MethodSpecies / strain
Species / strain / cell typeother:
Details on mammalian cell type (if applicable)
Chinese hamster lung(CHL/IU) cell
Metabolic activation
with and without
Metabolic activation system
S9 mix: Rat liver, induced with phenobarbital and 5,6- benzoflavone
Test concentrations with justification for top dose
Cell-growth inhibition test was conducted up to the limited concentration of 3000 μg/mL (maximum
concentration to be prepared)-Short term treatment, +/-S9 mix: concentration of 50% cell-growth inhibition was determined as375-750 μg/mL-Continuous treatment (24 h): concentration of 50% cell-growth inhibition was determined as 1
87.5-375 μg/mL-Continuous treatment (48 h): concentration of 50% cell-growth inhibition was determined as 187.5
μg/mL
Vehicle / solvent
DMSO
Controls
Untreated negative controlsno21

Negative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substanceother: 1-Methyl-3nitro-1-nitrosoguanidine (without S9 mix) 3,4-Benzo[a]pyrene (with S9 mix)
Details on test system and experimental conditions
METHOD OF APPLICATION: Exposure duration: [short-term treatment]:6 hrs + 18 hr, [continuous
treatment]: 24h
NUMBER OF CELLS EVALUATED: 200 cells /concentration (100 cells/plate x 2)
Plates/test: 4
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 concentration gr
oup. When frequencies of chromosomal aberrations were significantly increased in >=2 concentrationgroups, and when concentration dependent increase was observed, it was judged to be positive.

Results and discussion
Test results
Key result
trueSpecies / strainother: Chinese hamster lung(CHL/IU) cells
Metabolic activation
with and without
Genotoxicity
positive
Cytotoxicity / choice of top concentrations
cytotoxicity
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/PDF32492-61-8f.pdf
Tables (in English) are attachted to this document. Please download the export file to see the Tables.

22

Overall remarks, attachments
Attachments
Remarks
Tables for chromosome aberration tests

Applicant's summary and conclusion
Conclusions
4,4'-Isopropylidenediphenol, ethoxylated induced structural aberrations for the short-term study withand without S9 mix. Positive and vehicle control groups were valid.
Executive summary
In an in vitro chromosomal aberration test using CHL/IU cells (OECD TG 473), positive results wereobtained with or without metabolic activation.

23

Toxicity to reproduction
ENDPOINT_STUDY_RECORD: Toxicity to reproduction.001

UUID: 127203f9-63e8-4583-90a4-8ce936e9259b
Dossier UUID:
Author:Date: 2022-12-16T11:58:59.455+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, ethoxylated / 32492-61-8

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

Materials and methods
24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, ethoxylated
Specific details on test material used for the study- Name of test material (as cited in study report): 4,4'-isopropylidenediphenol, ethoxylated- Analytical purity: > 99%- Storage condition of test material: at a cold (temperature 2-6°C) and dark place, with airtight stopper.
- 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., Atsugi Breeding Center.
- Age at study initiation: 10 weeks old- Weight at study initiation: male 361 g (334-396 g), female 235 g (216-260 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 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: 22.1-25.0°C)- Humidity (%): 55±10% (actual humidity: 46-60%)- Air changes (per hr): >10- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light (light: 7:00~19:00)
25

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: 42-47 days including 14 days premating, 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)

Dose / conc.
1000

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 1000 mg/kg bw/day)Control animals
yes, concurrent vehicle26

Details on study design- Dose selection rationale: Based on the results of a 14-day preliminary study, the highest dose of1000 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 and 500 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 500 mg/kg bw/day or more, salivation, low value trend of urinary ketone
bodies, high value trend of total cholesterol and liver weight were observed. At 1000 mg/kg bw/day,high value trend of blood calcium, and reduced prothrombin time 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.
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/group27

- 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 and uterus.]
Postmortem examinations (offspring)
SACRIFICE- The F1 offspring were sacrificed at 4 days of age.
GROSS NECROPSY- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, andabdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGTHS- Not examined.
28

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, non-treatment-related
Description (incidence and severity)
See 7.5.1
Mortality
no mortality observed
Body weight and weight changes
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1
Food consumption and compound intake (if feeding study)no effects observed
29

Food efficiency
not examined
Water consumption and compound intake (if drinking water study)
not examined
Ophthalmological findings
not examined
Haematological findings
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1
Clinical biochemistry findings
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1
Urinalysis findings
no effects observed
Behaviour (functional findings)
no effects observed
Immunological findings
not examined
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1
Gross pathological findings
no effects observed
Neuropathological findings
not examined
Histopathological findings: non-neoplastic
effects observed, treatment-related
Description (incidence and severity)
See 7.5.1
Histopathological findings: neoplastic
not examined

Reproductive function / performance (P0)
Reproductive function: oestrous cycle
no effects observed
Reproductive function: sperm measures
no effects observed
Reproductive performanceno effects observed

Effect levels (P0)30Key result
true
Dose descriptor
NOAEL
Effect level1000

mg/kg bw/day (actual dose received)

Based ontest mat.
Sexmale/female
Basis for effect level
other: No effects on reproduction

Results: F1 generation
General toxicity (F1)Clinical signs
no effects observed
Mortality / viability
no mortality observed
Body weight and weight changes
no effects observed
Gross pathological findings
no effects observed

Effect levels (F1)
Key result
true
Dose descriptor
NOAEL
Generation
F1
Effect level1000

mg/kg bw/day (actual dose received)

Based ontest mat.
Sexmale/female
Basis for effect level
other: No effects on development

Any other information on results incl. tables
31

Figures and Tables (in English) are available in the following full report of the study.
http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF32492-61-8d.pdf

Applicant's summary and conclusion
Executive summary
In the combined repeated-dose toxicity study together with a toxicity screening test of reproduction anddevelopment (OECD TG422) described above, reproduction and development were not observed to beaffected. The NOAEL for the toxicity of 4,4'-isopropylidenediphenol, ethoxylated to rat reproduction anddevelopment was estimated to be 1000 mg/kg bw/day (the highest dose tested).

32

DOMAIN
Substance
SUBSTANCE: 4,4'-Isopropylidenediphenol, ethoxylated
UUID: 3361b877-d877-4ef7-9b93-95cba0844f45
Dossier UUID:
Author:Date: 2022-12-16T12:27:12.767+09:00
Remarks:
Substance name
4,4'-Isopropylidenediphenol, ethoxylated
Other substance identifiers
Identifier
CAS number
Identity
32492-61-8
Legal entity
National Institute of Health Sciences / Kawasaki / Japan

Identification of substance
Reference substance
4,4'-Isopropylidenediphenol, ethoxylated / 32492-61-8
EC number

EC name

CAS number

CAS name

32492-61-8

poly(oxy-1,2-ethanediyl),alpha,alpha'phenylene]bis[omega-hydroxy-

IUPAC name

Type of substanceType of substancepolymerRole in the supply chain
Manufacturer
false
Importer
false
Only representative
false
33

[(1-methylethylidene)di-4,1-

Downstream user
false

34

References
Reference Substances
REFERENCE_SUBSTANCE: 4,4'-Isopropylidenediphenol,
ethoxylated
UUID: 2a195910-823f-4f39-9d75-df85cfc04647
Dossier UUID:
Author:Date: 2022-12-16T11:40:03.381+09:00
Remarks:
Reference substance name
4,4'-Isopropylidenediphenol, ethoxylated

Inventory
CAS number
32492-61-8
CAS namepoly(oxy-1,2-ethanediyl),alpha,alpha'- [(1-methylethylidene)di-4,1-phenylene]bis[omega-hydroxy-

Molecular and structural information
Structural formula

Remarks[Molar ratio] 1 mole:0.0%, 2 moles: 5.6%, 3 moles: 16.9%, 4 moles:23.3%, 5 moles: 21.1%, 6 moles: 15.8%, 7 moles: 8.2%, 8 moles: 4.0%, >= 9 moles: 5.1%

35

Test Materials
TEST_MATERIAL_INFORMATION: 4,4'Isopropylidenediphenol, ethoxylated
UUID: 58a72914-84d0-48e3-986e-f8e6d37e3d07
Dossier UUID:
Author:Date: 2022-12-16T11:44:12.638+09:00
Remarks:Name
4,4'-Isopropylidenediphenol, ethoxylated

Composition
Composition
Reference substance
4,4'-Isopropylidenediphenol, ethoxylated / 32492-61-8
EC number

EC name

CAS number

CAS name

32492-61-8

poly(oxy-1,2-ethanediyl),alpha,alpha'phenylene]bis[omega-hydroxy-

IUPAC name36[(1-methylethylidene)di-4,1-

Literatures
LITERATURE: A combined repeated dose/
reproductive developmental toxicity study of
4,4'-Isopropylidenediphenol, ethoxylated by oral
administration in rats.
UUID: c3bab17e-0137-47ed-b811-e57f1f580c8c
Dossier UUID:
Author:Date: 2019-03-22T10:30:43.000+09:00
Remarks:

General information
Reference Typestudy report
Title
A combined repeated dose/reproductive developmental toxicity study of 4,4'-Isopropylidenediphenol,
ethoxylated by oral administration in rats.
Author
Ministry of Health, Labor and Welfare, Japan
Bibliographic source
Japan Existing Chemical Data Base (JCDB)
Testing facility
Research institute for animal science in biochemistry and toxicology (RIAS)
Report number
06-12337

LITERATURE: In Vitro Chromosomal Aberration
Test of poly(oxy-1,2-ethanediyl),alpha,alpha'- [(1methylethylidene)di-4,1-phenylene]bis[omega-hydroxyon Cultured Chinese Hamster Cells
UUID: 73366170-1230-469e-8ac5-4388a11e323c
Dossier UUID:
Author:Date: 2019-02-15T09:57:10.000+09:00
Remarks:

General information
Reference Typestudy report
Title
In Vitro Chromosomal Aberration Test of poly(oxy-1,2-ethanediyl),alpha,alpha'- [(1-methylethylidene)
di-4,1-phenylene]bis[omega-hydroxy- on Cultured Chinese Hamster Cells
Author
MHLW, Japan
Bibliographic source
http://dra4.nihs.go.jp/mhlw_data/jsp/SearchPageENG.jsp
Testing facility
Research Institute for Animal Science in Biochemistry and Toxicology (RIAS)

38

LITERATURE: Reverse Mutation Test of poly(oxy-1,2ethanediyl),alpha,alpha'- [(1-methylethylidene)di-4,1phenylene]bis[omega-hydroxyUUID: b4cfffab-f224-43b9-89b6-ad7d9aa6328c
Dossier UUID:
Author:Date: 2019-02-13T16:02:43.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Reverse Mutation Test of poly(oxy-1,2-ethanediyl),alpha,alpha'- [(1-methylethylidene)di-4,1-phenylene]bis[omega-hydroxyAuthor
Ministry of Health, Labour and Welfare (MHLW), Japan
Bibliographic source
JECDB(http://dra4.nihs.go.jp/mhlw_data/jsp/SearchPageENG.jsp)
Testing facility
Research Institute for Animal Science in Biochemistry and Toxicology (RIAS)

39

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 systemIUCLID440

ID16558402024DIV750

41