Name: OECD_SIDS / SUBSTANCE : Ethene, 1,1-difluoro-, homopolymer / 24937-79-9 Fri, 16
Dec 2022, 16:44:47+0900 /Legal entity owner: National Institute of Health Sciences
Printing date: 2022-12-16T16:44:47.960+09:00

iTable of Contents
0/0 ............................................................................................................................. 1
National Institute of Health Science ..................................................................... 2
Ethene, 1,1-difluoro-, homopolymer ....................................................................... 3
1 General information .................................................................................. 3
1.1 Identification ................................................................................. 3
Identification ............................................................................... 3
Identification ...................................................................... 3
1.10 Assessment approach (assessment entities) ................................. 4
Assessment approach (assessment entities) ................................ 4
7 Toxicological information ......................................................................... 5
7.5 Repeated dose toxicity ................................................................... 5
7.5.1 Repeated dose toxicity: oral ................................................. 5
Repeated dose toxicity: oral.001 ........................................... 5
7.6 Genetic toxicity ............................................................................ 14
7.6.1 Genetic toxicity in vitro ...................................................... 14
Genetic toxicity in vitro.001 ................................................ 14
Genetic toxicity in vitro.002 ................................................ 19
7.8 Toxicity to reproduction ............................................................... 23
7.8.1 Toxicity to reproduction ..................................................... 23
Toxicity to reproduction.001 ............................................... 23
References ................................................................................................................ 33
Reference Substances ...................................................................................... 33
Ethene, 1,1-difluoro-, homopolymer ............................................................. 33
Test Materials .................................................................................................. 34
Ethene, 1,1-difluoro-, homopolymer ............................................................. 34
Literatures ....................................................................................................... 35
Combined repeated dose toxicity study with the reproductive/
developmental toxicity screening test of poly(vinylidene fluoride) by oral
administration in rats ................................................................................ 35
In Vitro Chromosomal Aberration Test of Ethene, 1,1-difluoro-,homopolymer on Cultured Chinese Hamster Cells. ...................................... 36
Reverse Mutation Test of Ethene, 1,1-difluoro-, homopolymer on Bacteria. ..... 37
Legal Entities ................................................................................................... 38
National Institute of Health Sciences, Japan .............................................. 38ii

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Dossier header
Dossier submission type
Name
OECD SIDS
Versioncore 7.0
Name (given by user)

Dossier subject
Dossier subject
Ethene, 1,1-difluoro-, homopolymer / 24937-79-9
Public namePoly(vinylidene fluoride)
Submitting legal entity
National Institute of Health Science
Dossier creation date/time
Fri, 16 Dec 2022, 16:44:47+0900
Used in category

1

LEGAL_ENTITY: National Institute of Health
Science
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General information
Legal entity nameNational Institute of Health Science2

Ethene, 1,1-difluoro-, homopolymer
General information
Identification
Identification
SUBSTANCE: Ethene, 1,1-difluoro-, homopolymer

UUID: 58fabed0-ffb6-4832-a52a-68b0254373e5
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Author:Date: 2022-12-16T16:44:37.569+09:00
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Substance name
Ethene, 1,1-difluoro-, homopolymer
Public namePoly(vinylidene fluoride)
Legal entity
National Institute of Health Sciences, Japan
Contact persons

Identification of substance
Reference substance
Ethene, 1,1-difluoro-, homopolymer / 24937-79-9
EC number

EC name

CAS number

CAS name

24937-79-9
IUPAC nameRole in the supply chain
Manufacturer
false
Importer
false
Only representativefalse
Downstream user
false

3

Assessment approach (assessment entities)
FIXED_RECORD: Assessment approach
UUID: 13df30ec-da98-39fe-86c8-ad15f57e5bde
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Author:Date: 2020-03-24T16:02:19.000+09:00
Remarks:4

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

UUID: 6b72b7b2-9dae-4e5c-8848-0458217e8135
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Author:Date: 2022-12-16T16:40:02.433+09:00
Remarks:

Administrative data
Endpoint
short-term repeated dose toxicity: oral
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
other: The study was conducted in accordance with Test Guidelines and under GLP
Cross-reference
Reason / purpose for cross-reference
reference to same study 7.8.1 Toxicity to reproduction: Toxicity to reproduction. 001
Related information
OECD / Toxicity to reproduction / Toxicity to reproduction.001 / Ethene, 1,1-difluoro-, homopolymer /24937-79-9

Data source
Reference
Combined repeated dose toxicity study with the reproductive/developmental toxicity screening test of /Ministry of Health, Labour and Welfare (MHLW), Japan / study report
Data accessdata published5

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
Ethene, 1,1-difluoro-, homopolymer
Specific details on test material used for the study- Name of test material (as cited in study report): Ethene, 1,1-difluoro-, homopolymer- Analytical purity: 100%
- Storage condition of test material: Cold and dark place (3 - 6°C)
- Stability under test conditions: The stability of test material was identified by analysis of theremainder.

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: 383 g (353-423 g), Female: 246 g (224-270 g)- Housing: Animals were individually housed in bracket-type metallic wire-mesh cages (254W × 350D
× 170H mm), from gestation day 17 to lactation day 4, Dams were bred individually or with individual
littermates in plastic cages (340W x 400D x 185H mm) and bedding.
- Diet: Solid feed (NMF: Oriental Yeast Co., ltd.) was given ad libitum.
- Water: Tap water was given ad libitum.
- Acclimation period: 17 days
ENVIRONMENTAL CONDITIONS
6

- Temperature (°C): 23±3 (actual temperature: 23-25°C)- Humidity (%): 50±20% (actual humidity: 38-54%)- Air changes (per hr): 10-15- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light (light: 7:00~19:00)

Administration / exposure
Route of administration
oral: gavage
Vehiclecorn 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
Details on analytical verification of doses or concentrations
Test suspensions at each concentration to be used for males in week 1 and six week of admi
nistration were analyzed by gravimetric method at BoZo Research Center Inc. Results showed thatthe concentration of test article in each concentration was 99.0 to 102.5% of the nominal conc
entration and both values were within the acceptable range (concentration: percentage of nominal
concentration, 100±10%)Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating(P)Females: 42-46 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.
100

mg/kg bw/day (actual dose received)

Dose / conc.
300

mg/kg bw/day (actual dose received)

Dose / conc.
1000

mg/kg bw/day (actual dose received)

7

No. of animals per sex per dose
Main group: 12 females/dose (0, 100, 300, and 1000 mg/kg bw/day), 7, 12, 12, and 7 males/dose (0,100, 300, and 1000 mg/kg bw/day)Satellite group: 5 females/dose (0 and 1000 mg/kg bw/day)Recovery group: 5 males/dose and 5 females (satellite group)/dose (0 and 1000 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 of1000 mg/kg bw/day was selected as an expected obvious toxic dose, and the lowest dose of 100 mg/
kg bw/day was selected as an expected no toxic dose. The middle dose levels of 300 mg/kg bw/day
were selected.
[14-day preliminary study]
A 14-day repeated dose oral toxicity test (Crl:CD(SD) rats, doses: 0, 100, 300 or 1000 mg/kg bw/day).
Even in the 1000 mg/kg bw/day group, no effects related to the test substance were observed ingeneral condition, body weight, food consumption, hematology, blood biochemistry, organ weight,
and necropsy.
- Rationale for animal assignment (if not random): Body weight-balanced randomization

Examinations
Observations and examinations performed and frequency
CAGE SIDE OBSERVATIONS: Yes- Time schedule: 3 times/day (before administration, immediately after administration and 2 hours
after administration) during the administration period. Once a day during the recovery period.
DETAILED CLINICAL OBSERVATIONS: Yes- Time schedule:
Male main and female satellite groups: once before the start of administration, once every weekly
during the administration.
Female main group: once before the start of administration, days 1, 7, 14 and 20 of gestation, and day
4 of lactation.
Male and female recovery groups: once before the start of administration, once every weekly during the administration and recovery periods.
BODY WEIGHT: Yes- Time schedule for examinations:
Males in the main and females satellite groups were weighed on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32,
36, 39 and 42 of administration and on the day of necropsy, and males and females in the recovery
groups were weighed on days 1, 4, 8, 11 and 14 of recovery and on the day of necropsy in addition to
the measurement days for males in the main groups.
Females in the main groups were weighed on days 1, 4, 8, 11 and 15 of administration (uncopulated
animals were weighed on days 18 and 22 of administration as well), days 0, 4, 7, 11, 14, 17 and 20 of
gestation, days 0 and 4 of lactation and the day of necropsy.
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 females satellite groups on days 1, 4, 8, 11, 15, 32, 36, 39 and 42 of admini
stration; males and females in the recovery groups on days 1, 4, 8, 11 and 14 of recovery in addition to
the measurement days for males in the main groups; and females in the main groups on days 1, 4, 8,
11 and 15 of administration, days 1, 4, 7, 11, 14, 17 and 20 of gestation and days 2 and 4 of lactation.
OPHTHALMOSCOPIC EXAMINATION: No
8

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:
All animals/sex/group (Control and 1000 mg/kg/day),5 animals/sex/group (100 and 300 mg/kg/day)- Parameters examined: red blood cell count, hemoglobin, hematocrit, mean corpuscular volume,
mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, reticulocyte percentage, platelet count, white blood cell count, differential white blood cell count, absolute number of each
white blood cell, prothrombin time, activated partial thromboplastin time, fibrinogen.
CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: At the end of administration period, or at the end of recovery p
eriod in both sexes- Animals fasted: Yes- How many animals:
All animals/sex/group (Control and 1000 mg/kg/day),5 animals/sex/group (100 and 300 mg/kg/day)- Parameters checked: ALP, total cholesterol, triglyceride, phospholipids, total bilirubin, glucose, bloodurea nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phosphorus, total protein, al
bumin, A/G ratio, AST (GOT), ALT (GPT), LDH, γ-GTP
URINALYSIS: Yes- Time schedule for collection of urine: final week of administration (days 36 to 37 of administration)and in the final week of recovery (days 8 to 9 of recovery)- Metabolism cages used for collection of urine: Yes
A urine collector to collect four-hour urine samples under fasting but ad libitum drinking conditions, fo
llowed by collection of 20-hour urine samples under ad libitum feeding and drinking conditions.
- How many animals: 5 animals/group- Parameters checked: pH, protein, ketones, glucose, occult blood, bilirubin, urobilinogen, color,
sediment, urine volume (4-hour volume), osmotic pressure, urine volume (20-hour volume), water intake (24-hour volume)
BLOOD HORMONE: Yes- Time schedule for collection of serum: Same as clinical chemistry- Animals fasted: Yes- How many animals:
All animals/sex/group (Control and 1000 mg/kg/day),5 animals/sex/group (100 and 300 mg/kg/day)- Parameters checked: Triiodothyronine (T3), Thyroxin (T4), and thyroid stimulating hormone (TSH)
NEUROBEHAVIOURAL EXAMINATION: Yes- Time schedule for examinations:
Males in the main groups: final week of administration (day 40 of administration)
Females in the main groups: lactation day 4 (day 42 to day 44 of administration) after necropsy of F1
pups
Males and females in the recovery groups: final week of administration (day 40 of administration) andin the final week of recovery (day 12 of recovery).
- Dose groups that were examined: All dose groups (5 animals/sex/group)- Battery of functions tested:
1) Manipulative Test. Auditory response, approach response, touch response, tail pinch response, pu
pillary reflex, aerial righting reflex, landing foot splay
2) Measurement of Grip Strength. Following manipulative test, grip strength of forelimb and hind limb
was measured by CPU gauge MODEL-RX-5 (AIKOH Engineering Co., Ltd.).
3) Measurement of Motor Activity. Following measurement of grip strength, motor activity wasmeasured by a motor activity sensor for experimental animals NS-AS01 (Neuro Science, Inc). The me9asurement was conducted for 1 hour, and measured values at 10-minute intervals and from 0 to 60
minutes were collected.
Sacrifice and pathology
GROSS PATHOLOGY: Yes
ORGAN WEIBHT: Yes [brain, pituitary, thyroids (including parathyroids), adrenal gland, thymus, spleen,
heart, liver, kidney, testis, epididymis, ovary, uterus]
HISTOPATHOLOGY: Yes, [cerebrum, cerebellum (including pons) , pituitary, spinal cord (thoracic), sc
iatic nerve, eye ball, thyroid, parathyroid, adrenal glands, thymus, spleen, submandibular lymph nod
es, mesenteric lymph nodes, heart, trachea, lung (including bronchial), stomach, duodenum, jejunum,
ileum, cecum, colon, rectum, liver, kidney, bladder, testis, epididymis, ovary, uterus, vagina, prostate,seminal vesicles, sternum and femur (including bone marrows),and macroscopic lesions]
Statistics
The data were analyzed for homogeneity of variance by the Bartlett test. If variances were
homogeneous, data was analyzed by the Dunnett test, whereas heterogeneous data was analyzed by
the Dunnett type mean rank test (p<0.05, two-sided).
In the recovery test, these values of two groups were analyzed by F test. If variances were homogeneo
us, data was analyzed by the Student t-test, whereas heterogeneous data was analyzed by the AspinWelch t-test (p<0.05, two-sided).

Results and discussion
Results of examinations
Clinical signs
no effects observed
Mortality
no mortality observed
Body weight and weight changes
no effects observed
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
no effects observed
Clinical biochemistry findings
no effects observed
Description (incidence and severity)
Including blood hormones (T3, T4, TSH)
Urinalysis findings
no effects observed
10Behaviour (functional findings)
no effects observed
Immunological findings
not examined
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Gross pathological findings
no effects observed
Neuropathological findings
not examined
Histopathological findings: non-neoplastic
no effects observed
Histopathological findings: neoplastic
not examined
Details on results
CLINICAL SIGNS AND MORTALITY:
Mortality: There was no death.
Clinical signs: There were no effects related to the test substance in any groups at the dosing andrecovery periods.
DETAILED CLINICAL OBSERVATIONS: There were no changes related to the test substance in anygroups at the dosing and recovery periods.
BODY WEIGHT:
There were no changes related to the test substance in any groups at the dosing and recovery periods.
FOOD CONSUMPTION:
There were no changes related to the test substance in any groups at the dosing and recovery peri
ods.
URINALYSIS:There were no changes related to the test substance in any groups at the dosing and recovery
periods.
NEUROBEHAVOURAL EXAMINATION: There were no changes related to the test substance in anygroups at the dosing and recovery periods.
HAEMATOLOGY:
There were no changes related to the test substance in any groups at the end of dosing and recovery
periods.
CLINICAL CHEMISTRY (Including blood hormones (T3, T4, TSH)):
There were no changes related to the test substance in any groups at the end of dosing and recovery
periods.
ORGAN WEIGHTS:[At the end of dosing period]: Increases in absolute and relative weights of pituitary were observed inmating females receiving 1000 mg/kg bw/day.
[At the end of recovery period]: There were no changes related to the test substance in any groups.

11

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:
There were no changes related to the test substance in any groups at the end of dosing and recovery
periods.

Effect levels
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: There were no changes related to the test substance in any groups.

Any other information on results incl. tables
Figures and Tables (in English) are available in the following full report of the study.
https://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF24937-79-9d.pdf

Applicant's summary and conclusion
Conclusions
The NOAEL for the rat repeated dose toxicity of ethene, 1,1-difluoro-, homopolymer was regarded as 1
000 mg/kg bw/day, the highest dose tested.
Executive summary
A combined repeated-dose toxicity study with the reproduction/developmental toxicity screening test
was done according to OECD TG 422. Male and female rats (12 animals/sex/dose) were administeredwith ethene, 1,1-difluoro-, homopolymer via oral gavage at doses of 0 [vehicle: corn oil], 100, 300, and
1,000 mg/kg bw/day. Males (12/dose) were treated with ethene, 1,1-difluoro-, homopolymer for 42 days,
which include a 14-day premating period and a subsequent mating period, while females (12/dose) weretreated for 42–46 days, including 14-day premating, mating, and gestation periods until lactation day 4.
Among the 12 males that were treated with 0 and 1,000 mg/kg bw/day, 5 were assigned as the recovery
group. Additional 10 females administered with 0 and 1,000 mg/kg bw/day were assigned as a satellite
12group and treated with ethene, 1,1-difluoro-, homopolymer for 42 days, with no mating, and examined
after a 14-day recovery period.
No deaths were recorded, and there are no changes in clinical signs, manipulative test, grip
strength, motor activity, body weight, food consumption, urinalysis, hematology, blood chemistry, grosspathological findings, and histopathological findings as a result of treatment in any of the dose groups
for both males and females at the end of the treatment and recovery periods. Although absolute andrelative weights of pituitary were significantly increased in the mating group females receiving 1,000
mg/kg bw/day at the end of the administration period, these changes were not considered to be
adverse effects since there were no histological abnormalities and effect on endocrine organs observed.
Since there is no toxicological alteration, the NOAEL for repeated-dose toxicity of ethene, 1,1-difluoro-,homopolymer was 1,000 mg/kg bw/day in rats.

13

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

UUID: a0f7c7bc-890b-49f4-acce-b078078cdd0c
Dossier UUID:
Author:Date: 2022-12-16T16:42:57.382+09:00
Remarks:

Administrative data
Endpoint
in vitro gene mutation study in bacteria
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
other: OECD Test Guideline study under GLP condition

Data source
Reference
Reverse Mutation Test of Ethene, 1,1-difluoro-, homopolymer on Bacteria. / Ministry of Health, Labourand Welfare (MHLW), Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
14

in vitro gene mutation study in bacteria
Deviationsno
GLP compliance
yesType of assay
bacterial reverse mutation assay
in vitro gene mutation study in bacteria

Test material
Test material information
Ethene, 1,1-difluoro-, homopolymer
Specific details on test material used for the study- Name of test material (as cited in study report): Ethene, 1,1-difluoro-, homopolymer- Analytical purity: 100%

MethodSpecies / strain
Species / strain / cell typeS. typhimurium TA 1535, TA 1537, TA 98 and TA 100
bacteria
Species / strain / cell type
E. coli WP2 uvr A pKM 101
bacteria
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
-S9 mix:
2.44, 4.88, 9.77, 19.5, 39.1, 78.1 μg/plate (TA100, TA1535, TA98, TA1537 strains)
313, 625, 1250, 2500, 5000 μg/plate (WP2uvrA/pKM101 strain)+S9 mix:
313, 625, 1250, 2500, 5000 μg/plate (TA100, TA1535, TA98, TA1537 strains),
313, 625, 1250, 2500, 5000 μg/plate (WP2uvrA/pKM101 strain)
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 78.1 μg/plate and above for S.
typhimurium TA strains without S9 mix.
Vehicle / solvent- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controlsno15

Negative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substanceother: -S9 mix: 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide, sodium azide and 2-Methoxy-6-chloro-9-[3-(2chloroethyl)-aminopropylamino]acridine 2HCl; +S9 mix: 2-aminoanthracene, benzo(a)pyrene
Details on test system and experimental conditions
METHOD OF APPLICATION: Preincubation
DURATION- Preincubation period: 20 min at 37°C
- Exposure duration:48 or 48.5 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.
StatisticsnoResults and discussion
Test results
Key result
trueSpecies / strain
S. typhimurium TA 1535
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity -S9 mix: 39.1 μg/plate or more
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid

16

Key result
trueSpecies / strain
S. typhimurium TA 1537
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity -S9 mix: 39.1 μg/plate or more
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid
Key result
trueSpecies / strain
S. typhimurium TA 98
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity -S9 mix: 39.1 μg/plate or more
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid
Key result
trueSpecies / strain
S. typhimurium TA 100
bacteria
Metabolic activation
with and without
17

Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity -S9 mix: 78.1 μg/plate or more
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid
Key result
trueSpecies / strain
E. coli WP2 uvr A pKM 101
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity
Vehicle controls validity
valid
Untreated negative controls validity
not examined
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.
https://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF24937-79-9e.pdf
Please also see the attached files (Tables in English)

Applicant's summary and conclusion
Conclusions
Interpretation of results (migrated information): negative
In a bacterial reverse mutation assay using Salmonella typhimurium TA100, TA1535, TA98, and TA
1537, and Escherichia coli WP2uvrA/pKM101 (OECD TG 471), ethene, 1,1-difluoro-, homopolymer was
negative with or without metabolic activation.

18

ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.002

UUID: 3d730d72-66ac-4216-9f5c-81212252ee18
Dossier UUID:
Author:Date: 2022-12-16T16:44:24.395+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
false
Used for classification
false
Used for SDS
false
Reliability
1 (reliable without restriction)
Rationale for reliability incl. deficiencies
other: OECD Test Guideline study under GLP condition

Data source
Reference
In Vitro Chromosomal Aberration Test of Ethene, 1,1-difluoro-, homopolymer on Cultured Chinese
Hamst / Ministry of Health, Labour and Welfare (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
19

Deviations
no
Qualifieraccording to guideline
Guideline
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
genetic toxicity in vitro, otherDeviationsno
GLP compliance
yesType of assay
other: in vitro mammalian chromosome aberration test

Test material
Test material information
Ethene, 1,1-difluoro-, homopolymer
Specific details on test material used for the study- Name of test material (as cited in study report): Ethene, 1,1-difluoro-, homopolymer- Analytical purity: 100%

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-S9 mix (short-term treatment): 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 ug/mL+S9 mix (short-term treatment): 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 ug/mL-S9 mix (continuous treatment, 24hr): 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 ug/mL-S9 mix (continuous treatment, 48hr): 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 ug/mL
Main study-S9 (short-term treatment): 512, 640, 800, 1000, 1250 ug/mL+S9 (short-term treatment): 410, 512, 640, 800, 1000 ug/mL-S9 (continuous treatment, 24hr): 1020, 1280, 1600, 2000, 2500 ug/mL-S9 (continuous treatment, 48hr): 512, 640, 800, 1000, 1250 ug/mL

Vehicle / solvent- Vehicle(s)/solvent(s) used: 0.5%CNC Na
20

Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substanceother: [-S9]: mitomycin C; [+S9]: cyclophosphamide
Details on test system and experimental conditions
METHOD OF APPLICATION: Exposure duration: [short-term treatment]:6 hrs + 18 hr, [continuous
treatment]: 24, 48 hrs
SPINDLE INHIBITOR: Colcemid
STAIN: Giemsa stain (2 v/v%) for 15 min.
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: 100 + 100 cells /concentration
DETERMINATION OF CYTOTOXICITY- Method: relative total growth
Evaluation criteria
For the evaluation of the frequencies of structural aberrations and of polyploidy induced, the following
criteria were employed. Appearance incidence of cell with chromosomal aberrations: Negative (-):
less than 5%, Equivocal(±): 5% or more and less than 10%, Positive(+): 10% or more
StatisticsnoResults and discussion
Test results
Key result
trueSpecies / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity
Vehicle controls validity
valid
Untreated negative controls validity
not examined
21

Positive controls validityvalid

Any other information on results incl. tables
Figures and Tables (in English) are available in the following full report of the study.
https://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF24937-79-9f.pdf

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

22

Toxicity to reproduction
Toxicity to reproduction
ENDPOINT_STUDY_RECORD: Toxicity to reproduction.001

UUID: d0b6a385-1c2e-4eb6-b155-1a7213a45699
Dossier UUID:
Author:Date: 2022-12-16T16:41:51.022+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
other: OECD Test Guideline study under GLP condition
Cross-reference
Reason / purpose for cross-reference
reference to same study 7.5.1 Repeated dose toxicity: oral: Repeated dose toxicity: oral. 001
Related information
OECD / Repeated dose toxicity: oral / Repeated dose toxicity: oral.001 / Ethene, 1,1-difluoro-,homopolymer / 24937-79-9

Data source
Reference
Combined repeated dose toxicity study with the reproductive/developmental toxicity screening test of /Ministry of Health, Labour and Welfare (MHLW), Japan / study report
Data accessdata published

Materials and methods
23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
Ethene, 1,1-difluoro-, homopolymer
Specific details on test material used for the study- Name of test material (as cited in study report): Ethene, 1,1-difluoro-, homopolymer- Analytical purity: 100%
- Storage condition of test material: at a room temperature (15-23°C), protected from light- 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: 383 g (353-423 g), Female: 246 g (224-270 g)- Housing: Animals were individually housed in bracket-type metallic wire-mesh cages (254W × 350D
× 170H mm), from gestation day 17 to lactation day 4, Dams were bred individually or with individual
littermates in plastic cages (340W x 400D x 185H mm) and bedding.
- Diet: Solid feed (NMF: Oriental Yeast Co., ltd.) was given ad libitum.
- Water: Tap water was given ad libitum.
- Acclimation period: 17 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 23±3 (actual temperature: 23-25°C)- Humidity (%): 50±20% (actual humidity: 38-54%)- Air changes (per hr): 10-15- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light (light: 7:00~19:00)
24

Administration / exposure
Route of administration
oral: gavage
Vehiclecorn oil
Details on exposure- Amount of vehicle (if gavage): 5 mL/kg- Dosing volume: 5 mL/kg
Details on mating procedure- M/F ratio per cage:1/1- Length of cohabitation: up to 4 days
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
Analytical verification of doses or concentrations
yes
Details on analytical verification of doses or concentrations
Test suspensions at each concentration to be used for males in week 1 and six week of admi
nistration were analyzed by gravimetric method at BoZo Research Center Inc. Results showed thatthe concentration of test article in each concentration was 99.0 to 102.5% of the nominal conc
entration and both values were within the acceptable range (concentration: percentage of nominal
concentration, 100±10%)Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating(P)Females: 41-46 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.
100

mg/kg bw/day (actual dose received)

Dose / conc.
300

mg/kg bw/day (actual dose received)

Dose / conc.
1000

mg/kg bw/day (actual dose received)

25

No. of animals per sex per dose
Main group:12 females/dose (0, 100, 300, and 1000 mg/kg bw/day), 7, 12, 12, and 7 males/dose (0,100, 300, and 1000 mg/kg bw/day)Satellite group: 5 females/dose (0 and 1000 mg/kg bw/day)Recovery group: 5 males/dose and 5 females (satellite group)/dose (0 and 1000 mg/kg bw/day)Control animals
yes, concurrent no treatment
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 100 mg/
kg bw/day was selected as an expected no toxic dose. The middle dose levels of 300 mg/kg bw/day
were selected.
[14-day preliminary study]
A 14-day repeated dose oral toxicity test (Crl:CD(SD) rats, doses: 0, 100, 300 or 1000 mg/kg bw/day).
Even in the 1000 mg/kg bw/day group, no effects related to the test substance were observed ingeneral condition, body weight, food consumption, hematology, blood biochemistry, organ weight,
and necropsy.
- Rationale for animal assignment (if not random): Body weight-balanced randomization

Examinations
Parental animals: Observations and examinations
CAGE SIDE OBSERVATIONS: Yes- Time schedule: 3 times/day (before administration, immediately after administration and 2 hours
after administration) during the administration period. Once a day during the recovery period.
DETAILED CLINICAL OBSERVATIONS: Yes- Time schedule:
Male main and female satellite groups: once before the start of administration, once every weekly
during the administration.
Female main group: once before the start of administration, days 1, 7, 14 and 20 of gestation, and day
4 of lactation.
Male and female recovery groups: once before the start of administration, once every weekly during the administration and recovery periods.
BODY WEIGHT: Yes- Time schedule for examinations:
Males in the main and females satellite groups were weighed on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32,
36, 39 and 42 of administration and on the day of necropsy, and males and females in the recovery
groups were weighed on days 1, 4, 8, 11 and 14 of recovery and on the day of necropsy in addition to
the measurement days for males in the main groups.
Females in the main groups were weighed on days 1, 4, 8, 11 and 15 of administration (uncopulated
animals were weighed on days 18 and 22 of administration as well), days 0, 4, 7, 11, 14, 17 and 20 of
gestation, days 0 and 4 of lactation and the day of necropsy.
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 females satellite groups on days 1, 4, 8, 11, 15, 32, 36, 39 and 42 of admini
stration; males and females in the recovery groups on days 1, 4, 8, 11 and 14 of recovery in addition to
the measurement days for males in the main groups; and females in the main groups on days 1, 4, 8,
11 and 15 of administration, days 1, 4, 7, 11, 14, 17 and 20 of gestation and days 2 and 4 of lactation.

26

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:
All animals/sex/group (Control and 1000 mg/kg/day),5 animals/sex/group (100 and 300 mg/kg/day)- Parameters examined: red blood cell count, hemoglobin, hematocrit, mean corpuscular volume,
mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, reticulocyte percentage, platelet count, white blood cell count, differential white blood cell count, absolute number of each
white blood cell, prothrombin time, activated partial thromboplastin time, fibrinogen.
CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: At the end of administration period, or at the end of recovery p
eriod in both sexes- Animals fasted: Yes- How many animals:
All animals/sex/group (Control and 1000 mg/kg/day),5 animals/sex/group (100 and 300 mg/kg/day)- Parameters checked: ALP, total cholesterol, triglyceride, phospholipids, total bilirubin, glucose, bloodurea nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phosphorus, total protein, al
bumin, A/G ratio, AST (GOT), ALT (GPT), LDH, γ-GTP
URINALYSIS: Yes- Time schedule for collection of urine: final week of administration (days 36 to 37 of administration)and in the final week of recovery (days 8 to 9 of recovery)- Metabolism cages used for collection of urine: Yes
A urine collector to collect four-hour urine samples under fasting but ad libitum drinking conditions, fo
llowed by collection of 20-hour urine samples under ad libitum feeding and drinking conditions.
- How many animals: 5 animals/group- Parameters checked: pH, protein, ketones, glucose, occult blood, bilirubin, urobilinogen, color,
sediment, urine volume (4-hour volume), osmotic pressure, urine volume (20-hour volume), water intake (24-hour volume)
BLOOD HORMONE: Yes- Time schedule for collection of serum: Same as clinical chemistry- Animals fasted: Yes- How many animals:
All animals/sex/group (Control and 1000 mg/kg/day),5 animals/sex/group (100 and 300 mg/kg/day)- Parameters checked: Triiodothyronine (T3), Thyroxin (T4), and thyroid stimulating hormone (TSH)
NEUROBEHAVIOURAL EXAMINATION: Yes- Time schedule for examinations:
Males in the main groups: final week of administration (day 40 of administration)
Females in the main groups: lactation day 4 (day 42 to day 44 of administration) after necropsy of F1
pups
Males and females in the recovery groups: final week of administration (day 40 of administration) andin the final week of recovery (day 12 of recovery).
- Dose groups that were examined: All dose groups (5 animals/sex/group)- Battery of functions tested:
1) Manipulative Test. Auditory response, approach response, touch response, tail pinch response, pu
pillary reflex, aerial righting reflex, landing foot splay
2) Measurement of Grip Strength. Following manipulative test, grip strength of forelimb and hind limb
was measured by CPU gauge MODEL-RX-5 (AIKOH Engineering Co., Ltd.).
3) Measurement of Motor Activity. Following measurement of grip strength, motor activity wasmeasured by a motor activity sensor for experimental animals NS-AS01 (Neuro Science, Inc). The me27

asurement was conducted for 1 hour, and measured values at 10-minute intervals and from 0 to 60
minutes were collected.
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.
During the pre-mating administration period, vaginal smear pictures were classified as proestrus,
estrus, metestrus or diestrus and examined for the frequency of estrus and interval between estruses(estrous cycle). During the mating period, vaginal smears were examined for the presence of sperm.
Sperm parameters (parental animals)
Parameters examined in all P male parental generations: testis weight, epididymis weight, histopatho
logical examinations for testes, epididymides, seminal vesicle 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, and weight gain.
GROSS EXAMINATION OF DEAD PUPS: Yes, for external and internal abnormalities.
Postmortem examinations (parental animals)
METHOD OF SACRIFICED: All animals were sacrificed by exsanguination under ether anesthesia.
SACRIFICE: Male main and female satellite animals: On next day after the last administration (Day43), Maternal animals: on Day 4 of lactation, and male and females recovery animals: on Day 14 of recovery.
GROSS PATHOLOGY: Yes
ORGAN WEIBHT: Yes [brain, pituitary, thyroids (including parathyroids), adrenal gland, thymus, spleen,
heart, liver, kidney, testis, epididymis, ovary, uterus]
HISTOPATHOLOGY: Yes, [cerebrum, cerebellum (including pons) , pituitary, spinal cord (thoracic), scia
tic nerve, eye ball, thyroid, parathyroid, adrenal glands, thymus, spleen, submandibular lymph nodes, mesenteric lymph nodes, heart, trachea, lung (including bronchial), stomach, duodenum, jejunum,
ileum, cecum, colon, rectum, liver, kidney, bladder, testis, epididymis, ovary, uterus, vagina, prostate,seminal vesicles, sternum and femur (including bone marrows),and macroscopic lesions]
Postmortem examinations (offspring)
SACRIFICE- The F1 offsprings were euthanized on PND4 by exsanguination under ether anesthesia.
GROSS NECROPSY: Yes- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, andabdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGTHS- Not examined.
Statistics
The data were analyzed for homogeneity of variance by the Bartlett test. If variances were
homogeneous, data was analyzed by the Dunnett test, whereas heterogeneous data was analyzed by
the Dunnett type mean rank test (p<0.05, two-sided).
In the recovery test, these values of two groups were analyzed by F test. If variances were homogeneo
us, data was analyzed by the Student t-test, whereas heterogeneous data was analyzed by the AspinWelch t-test (p<0.05, two-sided).
Reproductive indices
Each parameter was determined by the following equations:
Copulation index (%) = (No. of copulated animals / No. of mated animals) × 100
Fertility index (%) = (No. of pregnant females / No. of copulated females) × 100
Insemination index (%) = (No. of impregnated males / No. of copulated males) × 100
Gestation length (days) = No. of days from pregnancy 0 to delivery 0
Delivery index (%) = (No. of females which delivered liveborns / No. of pregnant females) × 100
28

Implantation index (%) = (No. of implantation sites / No. of corpora lutea) × 100
Stillborn index (%) = (No. of stillborn / No of liveborns and stillborns) × 100
Live birth index (%) = (No. of liveborn / No. of implantation sites) × 100
External abnormalities (%) = (No. of pups with external abnormalities / No. of liveborns) × 100
Sex ratio = No. of liveborns males / No. of liveborns
Offspring viability indices
Viability index on postnatal day 4 (%) = (No. of live pups on day 4 / No. of liveborns on day 0) × 100

Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
Clinical signs
no effects observed
Mortality
no mortality observed
Body weight and weight changes
no effects observed
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
no effects observed
Clinical biochemistry findings
no effects observed
Description (incidence and severity)
Including blood hormones (T3, T4, TSH)
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
29

Gross pathological findings
no effects observed
Neuropathological findings
not examined
Histopathological findings: non-neoplastic
no effects observed
Histopathological findings: neoplastic
not examined

Reproductive function / performance (P0)
Reproductive function: oestrous cycle
no effects observed
Reproductive function: sperm measures
not examined
Reproductive performanceno effects observed

Details on results (P0)1) Estrous Cycle
There were no animals showing abnormal estrous cycles, and there were no significant differences in
the average length of the estrous cycle between the control group and any treatment groups.
2) Results of Mating
There were no significant differences in the incidence of females with irregular estrus cycle, mating
period with the number of estrus and day of conceiving, copulation index, and fertility index between
the control group and any treatment groups.
3) Delivery Data and Delivery
There were no significant differences in the gestation length, number of corpora lutea, number of imp
lantation sites, implantation index, and delivery index between the control group and any treatmentgroups.
Organ weight findings
See 7.5.1

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

mg/kg bw/day (actual dose received)

Based ontest mat.
30

Sex
male/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

Overall reproductive toxicity
Key result
true
Reproductive effects observednoAny other information on results incl. tables
31

Figures and Tables (in English) are available in the following full report of the study.
https://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF24937-79-9d.pdf

Applicant's summary and conclusion
Conclusions
In the combined repeated oral dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422), there were no effects on reproductive and developmental parameters up
to 1000 mg/kg bw/day. The NOAEL for the rat reproductive/developmental toxicity of ethene, 1,1difluoro-, homopolymer was regarded as 1000 mg/kg bw/day, the highest dose tested.
Executive summary
A combined repeated-dose toxicity study with the reproduction/developmental toxicity screening test
was done according to OECD TG 422. Male and female rats (12 animals/sex/dose) were administeredwith ethene, 1,1-difluoro-, homopolymer via oral gavage at doses of 0 [vehicle: corn oil], 100, 300, and
1,000 mg/kg bw/day. Males (12/dose) were treated with ethene, 1,1-difluoro-, homopolymer for 42 days,
which include a 14-day premating period and a subsequent mating period, while females (12/dose) weretreated for 42–46 days, including 14-day premating, mating, and gestation periods until lactation day 4.
Among the 12 males that were treated with 0 and 1,000 mg/kg bw/day, 5 were assigned as the recovery
group. Additional 10 females administered with 0 and 1,000 mg/kg bw/day were assigned as a satellitegroup and treated with ethene, 1,1-difluoro-, homopolymer for 42 days, with no mating, and examined
after a 14-day recovery period.
No mortalities were recorded with any dose in the treatment period. There were also no effects on
reproductive toxicity (fertility and reproductive organs) and developmental toxicity up to the highest
dose. Since the effects were not even observed at 1,000 mg/kg bw/day administration, the NOAEL forthe reproduction and development toxicity was 1,000 mg/kg bw/day in rats.

32

References
Reference Substances
REFERENCE_SUBSTANCE: Ethene, 1,1-difluoro-,homopolymer
UUID: db0c1926-d11d-4c34-86dd-2e1f01a8813b
Dossier UUID:
Author:Date: 2022-12-12T16:15:58.924+09:00
Remarks:
Reference substance name
Ethene, 1,1-difluoro-, homopolymer

Inventory
CAS number
24937-79-9

33

Test Materials
TEST_MATERIAL_INFORMATION: Ethene, 1,1-difluoro-,homopolymer
UUID: b7f31c31-2461-4add-9952-ce918e0bba34
Dossier UUID:
Author:Date: 2022-12-12T16:06:58.890+09:00
Remarks:Name
Ethene, 1,1-difluoro-, homopolymer

34

Literatures
LITERATURE: Combined repeated dose toxicity study withthe reproductive/developmental toxicity screening test ofpoly(vinylidene fluoride) by oral administration in rats
UUID: 501cbd53-ea23-4a62-afc4-b636c00c9016
Dossier UUID:
Author:Date: 2020-03-24T11:49:15.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Combined repeated dose toxicity study with the reproductive/developmental toxicity screening test ofpoly(vinylidene fluoride) by oral administration in rats
Author
Ministry of Health, Labour and Welfare (MHLW), Japan
Bibliographic source
available in the web of Japan Existing Chemical Data Base (JECDB) https://dra4.nihs.go.jp/
mhlw_data/home/pdf/PDF24937-79-9d.pdf
Testing facility
BoZo Research Center
Report number
R-105235

LITERATURE: In Vitro Chromosomal Aberration Test of
Ethene, 1,1-difluoro-, homopolymer on Cultured Chinese
Hamster Cells.
UUID: 1b8db8a3-1553-4e0d-ad4c-e5ebb8553366
Dossier UUID:
Author:Date: 2020-03-17T15:50:22.000+09:00
Remarks:

General information
Reference Typestudy report
Title
In Vitro Chromosomal Aberration Test of Ethene, 1,1-difluoro-, homopolymer on Cultured Chinese
Hamster Cells.
Author
Ministry of Health, Labour and Welfare (MHLW), Japan
Bibliographic source
Japan Existing Chemical Data Base (JECDB) https://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF2
4937-79-9f.pdf
Testing facility
Bozo Research Center Inc.
Report number
M-140936

LITERATURE: Reverse Mutation Test of Ethene, 1,1difluoro-, homopolymer on Bacteria.
UUID: 1720bd45-bcf5-4f69-928d-7c145f7d72bc
Dossier UUID:
Author:Date: 2020-03-17T15:42:57.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Reverse Mutation Test of Ethene, 1,1-difluoro-, homopolymer on Bacteria.
Author
Ministry of Health, Labour and Welfare (MHLW), Japan
Bibliographic source
Japan Existing Chemical Data Base (JECDB) https://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF24
937-79-9e.pdf
Testing facility
Bozo Research Center Inc.
Report number
T-046837

Legal Entities
LEGAL_ENTITY: National Institute of Health Sciences,Japan
UUID: 0952b3b9-2d0c-4bc8-925e-b069be7789b7
Dossier UUID:
Author:Date: 2020-02-19T14:42:16.000+09:00
Remarks:

General information
Legal entity nameNational Institute of Health Sciences, Japan

38