Name: COMPLETE / SUBSTANCE : 1-propene, tetramer / 6842-15-5 Fri, 16 Dec 2022,
16:16:07+0900 /Legal entity owner: National Institute of Health Sciences
Printing date: 2022-12-16T16:16:08.007+09:00

iTable of Contents
0/0 ............................................................................................................................. 1
National Institute of Health Science ..................................................................... 2
1-propene, tetramer ............................................................................................. 3
CORE .......................................................................................................... 3
1 General information .......................................................................... 3
1.10 Assessment approach (assessment entities) ......................... 3
Assessment approach (assessment entities) ........................ 3
OECD .......................................................................................................... 4
D Health Effects .................................................................................. 4
60 Acute toxicity: oral .................................................................. 4
Acute toxicity: oral.001 ........................................................ 4
67 Repeated dose toxicity: oral .................................................... 8
Repeated dose toxicity: oral.001 ........................................... 870 Genetic toxicity in vitro ......................................................... 16
Genetic toxicity in vitro.001 ................................................ 16
Genetic toxicity in vitro.002 ................................................ 20
73 Toxicity to reproduction ........................................................ 24
Reproductive/developmental toxicity.001 ............................ 24
DOMAIN .................................................................................................... 31
Substance ......................................................................................... 31
Substance ................................................................................ 31
References ................................................................................................................ 32
Reference Substances ...................................................................................... 32
1-propene, tetramer ................................................................................... 32
Test Materials .................................................................................................. 33
1-Propene, tetramer ................................................................................... 33
1-Propene, tetramer ................................................................................... 34
1-Propene, tetramer ................................................................................... 35
1-Propene, tetramer ................................................................................... 36
Literatures ....................................................................................................... 37
Combined repeat dose and reproductive/developmental toxicity screening
test of 1-Propene, tetramer by oral administration in rats ............................. 37
In Vitro Chromosomal Aberration Test of 1-Propene, tetramer on Cultured
Chinese Hamster Cells. ............................................................................. 38
Reverse Mutation Test of 1-Propene, tetramer on Bacteria. .......................... 39
Single Dose Oral Toxicity Test of 1-Propene, tetramer in Rats ....................... 40
Legal Entities ................................................................................................... 41
National Institute of Health Sciences .......................................................... 41ii

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1-propene, tetramer / 6842-15-5
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LEGAL_ENTITY: National Institute of Health
Science
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General information
Legal entity nameNational Institute of Health Science21-propene, tetramer
CORE
General information
Assessment approach (assessment entities)
FIXED_RECORD: Assessment approach

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Remarks:3

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

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Administrative data
Endpoint
acute toxicity: oral
Type of information
experimental study
Adequacy of study
key study
Robust study summary
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
Single Dose Oral Toxicity Test of 1-Propene, tetramer in Rats / MHLW, Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
4Guideline
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Test type
acute toxic class method
Limit test
no

Test material
Test material information
1-Propene, tetramer

Test animals
Speciesratcommon species
Strainother: Crl:CD(SD)SexfemaleDetails on test animals or test system and environmental conditions
TEST ANIMALS- Source :Charles River Japan Inc.
- Age at study initiation: 9~10 weeks old- Weight at study initiation: females, 236 (233-238) g (1st step group), 237 (234-242) g (2nd), 237(232-241) g (3rd), 236 (233-240) g (4th)- Fasting period before study: Approximately 16 hrs- Housing: 3/cage- Diet (e.g. ad libitum): Ad libitum except fasting period for 16 hrs before administration to 3 hrs after administration- Water (e.g. ad libitum): Ad libitum- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 22±3 ℃(actual temperature: 21.2-22.1℃)- Humidity (%): 55 ± 10% (actual humidity: 58-62%)- Air changes (per hr): > 10 times/hr- Photoperiod (hrs dark / hrs light): 12 hrs light / 12 hrs dark

Administration / exposure
Route of administration
oral: gavage
Vehicleolive oil
Details on oral exposure- Amount of vehicle (if gavage): 5 ml/kg bw
Doses
300 mg/kg bw (1st and 2nd steps), 2000 mg/kg bw (3rd and 4th steps)
5No. of animals per sex per dose
3 (each step)
Control animals
noDetails on study design- Duration of observation period following administration: 14 days
- Frequency of observations: nearly successive observation (from time just to 1 hr after administration) and observation of every 2 hr (from 2 hr – 6 hr after administration) (day 0); twice a day (day 1); oncea day (from day 2-day14)- Frequency of weighing: just before administration (day 0), and 3,7 and 14 day after administration- Necropsy of survivors performed: yes

Results and discussion
Effect levels
Key result
false
Sex
female
Dose descriptor
LD50
Effect levelca. 5000mg/kg bw

Mortality
No deaths were observed in any group.
Clinical signs
other: Diarrhea was observed at 300 mg/kg bw. Decreased locomotor activity, diarrhea and soiled perineal region were observed at 2000 mg/kg bw.
Gross pathology
No changes related to the test substance were observed in any group.

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/PDF6842-15-5a.pdf

Applicant's summary and conclusion
Interpretation of results
Category 5 based on GHS criteria Migrated information
6

Conclusions
No deaths were observed at 300 and 2000 mg/kg bw. The LD50 was considered to be approximately
5000 mg/kg bw (GHS: 5).
Executive summary
The acute oral LD50 of 1-propene, tetramer was > 2,000 mg/kg bw in female rats based on a study
conducted according to OECD TG 423. No deaths were observed at 2,000 mg/kg bw. This substance at
300 mg/kg bw caused diarrhea and at 2,000 mg/kg bw caused decreased locomotor activity, diarrhea,
and soiled perineal region.

7

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

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Author:Date: 2022-12-16T16:13:23.471+09:00
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Administrative data
Endpoint
short-term repeated dose toxicity: oral combined repeated dose and reproduction / developmental
screening
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
Remarks
7.8.1 Reproductive/developmental toxicity.001

Data source
Reference
Combined repeat dose and reproductive/developmental toxicity screening test of 1-Propene, tetramer
b / MHLW, Japan / study report
Data accessdata published8

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

Test material
Test material information
1-Propene, tetramer

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 Laboratories Japan, Inc. Atsugi- Age at study initiation: 8 weeks- Weight at study initiation: Males: 264-308 g; Females: 178-225 g- Housing: bracket-type metallic wire-mesh cages (W 260 × D 380 × H 180 mm)- Diet: ad libitum- Water: ad libitum- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 20-24- Humidity (%): 41-58- Air changes: 10-15 times / hr
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure
Route of administration
oral: gavage
9Vehiclecorn oil
Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: Test substance was dissolved in corn oil for injection.
VEHICLE- Lot/batch no. (if required): VIR7200 produced by Nacalai Tesque, INC.
- Dosing volume: 5 mL/kg bw- Stability (test solutions): At least 9 days
- Storage condition of test solution: Room temperature
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 the HPLC method at Nisso chemical analysis service Co., Ltd. Results sho
wed that the concentration of the test article in each suspension was 99.7 to 108.2% of the nominal
concentration and both values were within the acceptable range (concentration: percentage of thenominal concentration, 100 ± 10%; C.V.: 10% or below)
Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating, mating, and thereafter 14 days(P) Females: 42–51 days including 14 days pre-mating, mating and gestation periods and the days unt
il day 4 of lactation. 42 days for satellite females (without mating).
Frequency of treatment
Once/day, 7 days/week
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 40, 150, and 600 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose
12 animals/sex/dose as a main dose group,
5* males and 5 females at 0 and 600 mg/kg bw/day as a satellite group (without mating)* From corresponding main dose groups
Control animals
yes, concurrent vehicle
Details on study design- Dose selection rationale: Doses in this test were set based on the results of the following dosesetting study: a 14-day repeated dose oral toxicity test (doses: 0, 30, 100, 300, and 1000 mg/kg bw/
day). In the dose-setting study, increased liver and kidney weights were observed at 300 mg/kg bw/
day and above, and diarrhea, mucous stool, low values of body weight and food consumption, highvalues of urine volume, ALT, urea nitrogen, creatinine and total cholesterol were observed at 1000
mg/kg bw/day. On the basis of these effects, a dose level of 600 mg/kg was selected as the maximu
m dose expecting to induce the toxic changes, and then dose levels of 150 and 40 mg/kg bw/day
were selected as a middle dose and a minimum dose levels, respectively, in accordance with a com
mon ratio of approximately 4.
- Rationale for animal assignment (if not random): Body weight-balanced randomization10

- Post-exposure recovery period in satellite groups: 14 days

Examinations
Observations and examinations performed and frequency
CAGE SIDE OBSERVATIONS: Yes- Time schedule:
Males and females: 2 times/day during the administration period 'before and after dosing) and therecovery period (am and pm)
DETAILED CLINICAL OBSERVATIONS: Yes
The functional observational battery testing (FOB) was performed on all animals. Among themeasures in the FOB, detailed clinical observations were made before the initiation of dosing. Ther
eafter, in males of the main groups, detailed clinical observations were made once a week. Also in females of the main groups, detailed clinical observations were made once a week in pre-mating andmating periods thereafter, and then those were made on days 1,7,14 and 20 of gestation, and on day
4 of lactation. For the satellite group, detailed clinical observations were made once a week in dosing
and recovery periods.
Sensory motor reflexes, forelimb and hindlimb grip strengths, and motor activity were measured
on week 6 of administration period (main/recovery group animals) and week 2 of recovery period(recovery group animals).
BODY WEIGHT: Yes- Time schedule for examinations: Males (main/recovery group): Days 1, 3, 5, 7, 10, 14, 21, 28, 35, 42,
and the day of necropsy (after ca. 16h-fasting) in dosing period
Males and females (recovery group): Days 1, 7, 14, and the day of necropsy (after ca. 16h-fasting) in recovery period
Females (main group): Twice a week during the precopulation period (days 1, 3, 5, 7, 10, and 14);
gestation days 0, 1, 3, 5, 7, 10, 14, 17, and 20; lactation days 0, 1, and 4; and the day of necropsy (afterca. 16 h-fasting)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption: Yes, same days of the measuring of body weight
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes- Time schedule for collection of blood: Blood was collected on the day of necropsy- Anaesthetic used for blood collection: Yes (pentobarbital sodium)- Animals fasted: Yes, 16-22h- How many animals: 5 sex/dose/group- Parameters checked in table were examined.
- Measurement of thyroid hormone: Yes (T3, T4, TSH)
CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: Same as hematology- Animals fasted: Same as hematology- How many animals: Same as hematology- Parameters checked in table were examined.
URINALYSIS: Yes- Time schedule for collection of urine: on week 6 of administration period (main/recovery group
animals) and week 2 of recovery period (recovery group animals).
- Metabolism cages used for collection of urine: Yes- Animals fasted: no fasting (3h- and 21h-urine)

11

Sacrifice and pathology
GROSS NECROPSY- Gross necropsy consisted of external and internal examinations including the brain (cerebrum,
cerebellum and pons), spinal cord, pituitary, thymus, thyroid gland (including parathyroid), adrenal
glands, spleen, heart, esophagus, stomach, liver, pancreas, submandibular gland, duodenum, jejunum, ileum (including Peyer's patches), cecum, colon, rectum, trachea, lung, kidney, bladder, testis, epididymis, prostate, seminal vesicles (including coagulating gland), ovary, uterus (the corners andneck), vagina, eye and Harder gland, mammary gland (right abdomen), femur (including the bonemarrow, right), mesenteric lymph nodes, submandibular lymph nodes, skeletal muscle (gastrocnemius), sciatic nerve and gross abnormal site (including the boundary areas between the normal and abnor
mal sites)
HISTOPATHOLOGY: Organs and tissues (same as gross necropsy)
Other examinations
Organ weight: Brian, pituitary gland, thyroids (including parathyroids), thymus, heart, liver, kidneys,
spleen, adrenal gland, thymus, testis, epididymis, prostate (ventral), seminal vesicles (including
coagulating gland and secretions), ovary, uterus

Statistics
The data were analyzed for homogeneity of variance by the Bartlett test. If variances were
homogeneous, data was analyzed by one-way ANOVA and the Dunnett test, whereas heterogeneous
data was analyzed by Kruskal-Wallis test and the Steel test.
For findings two or more grades was observed, data was analyzed by Kruskal-Wallis test and the Steeltest. For findings one grade was observed, data was analyzed by a multi-sample chi-square test anda two-sample chi-square test. For the comparison tests with the control group, the significance level
was 5%.

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)
effects observed, treatment-related
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
12Clinical biochemistry findings
effects observed, treatment-related
Description (incidence and severity)
including thyroid hormones (T3, T4, and TSH)
Urinalysis findings
effects observed, treatment-related
Behaviour (functional findings)
no effects observed
Description (incidence and severity)
see clinical signs.
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Gross pathological findings
effects observed, treatment-related
Histopathological findings: non-neoplastic
effects observed, treatment-related
Histopathological findings: neoplastic
not examined
Details on results
FOOD CONSUMPTION
Low values were observed in females of main group at 600 mg/kg bw/day on 3-5 day of dosing andon 1-3 and 3-5 days of gestation.
HAEMATOLOGY
In males, at the end of dosing period, low values of red blood cell count, hemoglobin level, and hema
tocrit were observed at 150 mg/kg bw/day and higher.
At the end of recovery period, low values of red blood cell count, hemoglobin level, and hematocrit,and high value of reticulocyte count were observed at 600 mg/kg bw/day.
In females, at the end of dosing period, low value of reticulocyte count was observed at 600 mg/
kg bw/day (main group) , and low value of red blood cell count and prolonged activated partial thromboplastin time were observed at 600 mg/kg bw/day (satellite group). No effects were observed at
the end of recovery period.
CLINICAL CHEMISTRY
In males, at 600 mg/kg bw/day: High values of α2-globulin fraction, gamma-GTP, total cholesterol,
and urea nitrogen, and low value of glucose were observed at the end of dosing period, and highvalues of gamma-GTP, urea nitrogen, and inorganic phosphorus were observed at the end of recovery
period.
In females, at 600 mg/kg bw/day: High values of gamma-GTP and low value of inorganic phosphor
us were observed at the end of dosing period (main group), and high values of α2-globulin fraction,
total cholesterol, and potassium, and low value of total bilirubin and sodium were observed at the end of dosing period (satellite group). Low value of A/G ration and albumin was observed at the end ofrecovery period.
On the thyroid hormone, high value of T4 was observed in females at the end of the recovery period.
URINALYSIS
Circular epithelial cells appeared in the urinary sediment of males at 600 mg/kg bw/day.
ORGAN WEIGHTS
In males, high value of kidney weight at 40 mg/kg bw/day and higher, high value of liver weight at
150 mg/kg bw/day and higher were observed at the end of the dosing period. High value of a kidneyweight was observed at 600 mg/kg bw/day at the end of the recovery end.
13

In females, high values of liver weight at 150 mg/kg bw/day and higher, thyroid weight at 600 mg/kg
bw/day, and kidney weight at 40 and 600 mg/kg bw/day were observed at the end of the dosing period (main group), and liver, kidney, and thyroid weights at 600 mg/kg bw/day were observed at the end of the dosing period (satellite group). Kidney and thyroid weights at 600 mg/kg bw/day were obser
ved at the end of the recovery period.
GROSS PATHOLOGY: See tables in the full report.
HISTOPATHOLOGY: See tables in the full report.
Main lesions were observed in the kidney and the liver in males, and were observed in the liver andthe thyroid in females.

Effect levels
Key result
false
Dose descriptor
NOAEL
Effect level40

mg/kg bw/day (actual dose received)

Based ontest mat.
Sex
male
Basis for effect level
other: anemia and increased liver weight
Key result
false
Dose descriptor
NOAEL
Effect level40

mg/kg bw/day (actual dose received)

Based ontest mat.
Sex
femaleBasis for effect level
other: increased liver weight

Target system / organ toxicity
14

Key result
false
Critical effects observed
not specified

Any other information on results incl. tables
Field content is not in a valid XML format and thus ignored!

Applicant's summary and conclusion
Executive summary
A combined repeated oral dose toxicity study with the reproduction/developmental toxicity screening
test was performed according to a Japanese guideline (similar to OECD TG 422). Male and female
rats (12 animals/sex/dose) were administered 1-propene, tetramer at 0, 40, 150, and 600 mg/kg bw/
day. Males were dosed for 42 days, including a 14-day pre-mating and mating periods. Females were
dosed for 40–45 days, including a 14-day pre-mating, mating, and gestation periods and the time until
day 4 of lactation. Five out of 12 males with administered doses of 0 and 600 mg/kg bw/day were
evaluated as a 14-day recovery group. In addition, 10 females/dose were administered 0 and 600 mg/
kg bw/day for 42 days without mating; they were examined after the administration period or after a
14-day recovery period. Regarding hematology parameters, anemia was observed at 150 mg/kg bw/
day and higher in males, with decreased red blood cell counts at 600 mg/kg bw/day in females without
mating. In the kidney, in males, α2u-globulin nephropathy was observed at 40 mg/kg bw/day and higher,
with increased kidney weight at 40 mg/kg bw/day and higher and basophilic changes in the tubularepithelium at 150 mg/kg bw/day and higher. Furthermore, necrosis of the tubular epithelium, increased
blood urea nitrogen level, and round epithelial cells in urinary sediments were observed in males at 600
mg/kg bw/day. These effects were considered to be caused by α2u-globulin accumulation in the kidneyas male rat specific disease, and were not relevant in human health. In the liver, in both sexes, increased
liver weight was observed at 150 mg/kg bw/day and higher, with centrilobular hepatocytes hypertrophy
at 600 mg/kg bw/day. Furthermore, increases in the α2-globulin fraction, γ-glutamyl transpeptidase,and total cholesterol levels and a decrease in glucose level were observed at 600 mg/kg bw/day inboth sexes. In the thyroid, in females, increased thyroid weight and hypertrophy of follicular cells wereobserved at 600 mg/kg bw/day, with thyroxin level increasing after the recovery period at this dose.
Hematology, kidney, and liver, but not thyroid, changes tended to resolve after the recovery period. On
the basis of anemia in males and increased liver weight in both sexes, NOAEL for repeated-dose toxicity
was determined to be 40 mg/kg bw/day in male and female rats.

15

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

UUID: IUC5-e1c75adb-a8dd-43ee-864e-bfc1af110861
Dossier UUID:
Author:Date: 2022-12-16T16:14:20.530+09:00
Remarks:

Administrative data
Endpoint
in vitro gene mutation study in bacteria Type of genotoxicity: gene mutation
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 1-Propene, tetramer on Bacteria. / MHLW, Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviations
no16

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

Test material
Test material information
1-Propene, tetramer

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
bacteria
Metabolic activation
with and without
Metabolic activation system
rat liver, induced by phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose
-S9 mix and + S9 mix: 156, 313, 625, 1250, 2500, 5000 μg/plate (all strains)
Vehicle / solvent- Vehicle(s)/solvent(s) used: Acetone
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controls
other: tests without all strains, and with vehicle, S9 mix or the highest dose
Positive controls
yes
Positive control substanceother: -S9 mix: 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (AF2:TA 100, TA98 & WP2 uvrA), sodium
azide (SA:TA1535) and 9-aminoacridine hydrochloride (9AA:TA1537). +S9 mix: 2-aminoanthracene(2AA:all strains).
Remarks
AF2 & 2AA were dissolved with DMSO, and SA & 9AA were dissolved with distilled water.
Details on test system and experimental conditions
RANGE-FINDING/SCREENING STUDIES:Concentration: 20-5000 μg/plate
17

Cytotoxic conc.: [-S9mix] No, [+S9mix] No.
Precipitate: Yes, >1000 μg/plate
METHOD OF APPLICATION: Preincubation
DURATION- Preincubation period: 20 min at 37 ℃
- Exposure duration:48 hrs
NUMBER OF PLATES: 3
NUMBER OF REPLICATIONS: 2
DETERMINATION OF CYTOTOXICITY- Method: other: growth inhibition
Evaluation criteria
In any strain(s) tested with or without S9 mix, when the mean number of revertant colonies per plateincreased twice more than that of the negative control and when the increase was shown to be dose-r
elated and reproducible, the chemical was judged mutagenic.
Statistics
No.

Results and discussion
Test results
Key result
false
Species / strain
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity
valid
Positive controls validity
valid
Key result
false
Species / strain
E. coli WP2 uvr A
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
Contamination with any other bacterias was not found.
Remarks on result
other: all strains/cell types tested Migrated from field 'Test system'.

Any other information on results incl. tables
Field content is not in a valid XML format and thus ignored!

Overall remarks, attachments
Attachments
Attached (sanitised) documents for publication
6842-15-5_Ames.xlsx / 36.463 KB (application/vnd.openxmlformatsofficedocument.spreadsheetml.sheet)

Applicant's summary and conclusion
Conclusions
Interpretation of results (migrated information):negative
Executive summary
In a bacterial reverse mutation assay using Salmonella typhimurium TA100, TA1535, TA98, and TA1537
and Escherichia coli WP2uvrA (similar to OECD TG 471), 1-propene, tetramer was negative with orwithout metabolic activation.

19

ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.002

UUID: IUC5-3058b6ae-b1d0-4a29-8507-f74af19ce5cf
Dossier UUID:
Author:Date: 2022-12-16T16:14:54.068+09:00
Remarks:

Administrative data
Endpoint
in vitro cytogenicity / chromosome aberration study in mammalian cells Type of genotoxicity:
chromosome aberration
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 1-Propene, tetramer on Cultured Chinese Hamster Cells. /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

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

Test material
Test material information
1-Propene, tetramer

MethodTarget gene
Chromosome
Species / strain
Species / strain / cell typeother: Chinese hamster lung(CHL/IU) cells
Metabolic activation
with and without
Metabolic activation system
rat liver, induced by phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose
-S9 mix (short-term treatment): 0, 53.1, 106, 213, 425 ug/mL+S9 mix (short-term treatment): 0, 213, 425, 850, 1700 ug/mL-S9 mix (continuous treatment, 24 h): 0, 53.1, 106, 213, 425 ug/mL-S9 mix (continuous treatment, 48 h): 0, 53.1, 106, 213, 425 ug/mL
Vehicle / solvent- Vehicle(s)/solvent(s) used:Acetone
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controlsno21

Positive controls
yes
Positive control substancecyclophosphamide
mitomycin C
Remarks
mitomycin C (without S9 mix), cyclophosphamide (with S9 mix)
Details on test system and experimental conditions
METHOD OF APPLICATION: Exposure duration: [continuous treatment]: 24, 48 hrs [short-term treatment]:6 hrs + 18 hr
SPINDLE INHIBITOR: Colcemid
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: 200 cells / dose
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 cells with chromosomal aberrations: Negative (-): < 5%; equivocal (±): 5-10%;
positive (+): > 10%.
Finally, the substance is positive when the incidence is considered to be dose-related and repro
ducible.
Statistics
not used.

Results and discussion
Test results
Key result
false
Species / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
with
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid
Key result
false
22

Species / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity 50% cell growth inhibition: 315.3 ug/mL (short), 336.7 ug/mL (24h continuous) and
219.2 ug/mL (48h continuous)
Vehicle controls validity
valid
Untreated negative controls validity
not examined
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.
http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF6842 -15 -5f.pdf

Applicant's summary and conclusion
Executive summary
An in vitro chromosomal aberration test using CHL/IU cells (OECD TG 473) showed positive.

23

Toxicity to reproduction
ENDPOINT_STUDY_RECORD: Reproductive/developmental toxicity.001

UUID: IUC5-e522e89f-3b32-4842-a874-9ca34277d649
Dossier UUID:
Author:Date: 2022-12-16T16:15:45.897+09:00
Remarks:

Administrative data
Endpoint
screening for reproductive / developmental toxicity based on test type (migrated information)
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
Remarks
7.5.1 Repeated dose toxicity: oral.001

Data source
Reference
Combined repeat dose and reproductive/developmental toxicity screening test of 1-Propene, tetramer
b / MHLW, Japan / study report
Data accessdata published

Materials and methods
24Test guideline
Qualifierequivalent or similar to guideline
Guideline
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction /Developmental Toxicity Screening Test)
GLP compliance
yes

Test material
Test material information
1-Propene, tetramer

Test animals
Speciesrat
Strainother: Crl: CD(SD)Sexmale/female
Details on test animals or test system and environmental conditions
TEST ANIMALS- Source: Charles River Laboratories Japan, Inc. Atsugi- Age at study initiation: 8 weeks- Weight at study initiation: Males: 264-308 g; Females: 178-225 g- Housing: bracket-type metallic wire-mesh cages (W 260 × D 380 × H 180 mm)- Diet: ad libitum- Water: ad libitum- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 20-24- Humidity (%): 41-58- Air changes: 10-15 times / hr
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure
Route of administration
oral: gavage
Vehiclecorn oil
Details on exposure
PREPARATION OF DOSING SOLUTIONS: Test substance was dissolved in corn oil for injection.
VEHICLE25

- Lot/batch no. (if required): VIR7200 produced by Nacalai Tesque, INC.
- Dosing volume: 5 mL/kg bw- Stability (test solutions): At least 9 days
- Storage condition of test solution: Room temperature
Details on mating procedure- M/F ratio per cage:1:1- Length of cohabitation:up to 14 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 administrati
on were analyzed by the HPLC method at Nisso chemical analysis service Co., Ltd. Results showedthat the concentration of the test article in each suspension was 99.7 to 108.2% of the nominal
concentration and both values were within the acceptable range (concentration: percentage of the nominal concentration, 100 ± 10%; C.V.: 10% or below)

Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating, mating, and thereafter 14 days(P) Females: 42–51 days including 14 days pre-mating, mating and gestation periods and the days
until day 4 of lactation. 42 days for satellite females (without mating).

Frequency of treatment
Once/day, 7 days/week
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 40, 150, and 600 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose
12 animals/sex/dose as a main dose group,
5* males and 5 females at 0 and 600 mg/kg bw/day as a satellite group (without mating)* From corresponding main dose groups
Control animals
yes, concurrent vehicle

Examinations
Parental animals: Observations and examinations
see 7.5.1 repeated dose toxicity: oral.001
26

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 P male parental generations: testes weight, epididymides weight
Litter observations
PARAMETERS EXAMINED: The following parameters were examined in F1 offspring:Number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, andweight gain.
GROSS EXAMINATION OF DEAD PUPS: Yes, for external and internal abnormalities.
Postmortem examinations (parental animals)
SACRIFICE- Male animals:Rats were euthanized by exsanguination under ether anesthesia on the day after the la
st administration.
- Maternal animals: Rats were euthanized by exsanguination under ether anesthesia on day 4 of lactat
ion.
GROSS NECROPSY- Gross necropsy consisted of external and internal examinations including the brain (cerebrum, cerebellum and pons), spinal cord, pituitary, thymus, thyroid gland (including parathyroid), adrenal glands,
spleen, heart, esophagus, stomach, liver, pancreas, submandibular gland, duodenum, jejunum, ileum(including Peyer's patches), cecum, colon, rectum, trachea, lung, kidney, bladder, testis, epididymis,
prostate, seminal vesicles (including coagulating gland), ovary, uterus (the corners and neck), vagina,
eye and Harder gland, mammary gland (right abdomen), femur (including the bone marrow, right),
mesenteric lymph nodes, submandibular lymph nodes, skeletal muscle (gastrocnemius), sciatic nerve
and gross abnormal site (including the boundary areas between the normal and abnormal sites)
ORGAN WEIGHT: Brian, pituitary gland, thyroids(including parathyroids), thymus, heart, liver, kidneys,
spleen, adrenal gland, thymus, testis, epididymis, prostate (ventral), seminal vesicles (including
coagulating gland and secretions), ovary, uterus
HISTOPATHOLOGY: See "Gross necropsy."
Postmortem examinations (offspring)
SACRIFICE- The F1 pups were sacrificed at PND 4 by exsanguination under ether anesthesia.
GROSS NECROPSY- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, andabdominal viscera.
Statistics
The data were analyzed for homogeneity of variance by the Bartlett test. If variances were
homogeneous, data was analyzed by one-way ANOVA and the Dunnett test, whereas heterogeneous
data was analyzed by Kruskal-Wallis test and the Steel test.
For findings two or more grades was observed, data was analyzed by Kruskal-Wallis test and the Steeltest. For findings one grade was observed, data was analyzed by a multi-sample chi-square test anda two-sample chi-square test. For the comparison tests with the control group, the significance level
was 5%.

27

Reproductive indices
Each parameter was determined by the following equations:
Duration of gestation (days) = day 0 of lactation – day 0 of gestation
Abnormal estrous cycle = (No. of female with abnormal estrous cycle / No. of females examined) ×100
Copulation index (males or females, %) = (No. of copulated males or females/No. of co-housed
males or females) × 100
Fertility index (%) = (No. of pregnant females/No. of copulated females) × 100
Gestation index (%) = (No. of females delivered liveborn pups/No. of pregnant females) × 100
Nursing index (%) = (No. of females nursing live pups on lactation day 4/No. of females with live pupsdelivery) × 100
Implantation index (per litter, %) = (No. of implantation sites/No. of corpora lutea) × 100
Delivery index (per litter, %) = (No. of pups born/No. of implantation sites) × 100
Sex ratio on Lactation day 0 = (No. of male pups born / No. of pups born) and (No. of live male pups /No. of live pups)
Sex ratio on Lactation day 4 = No. of live male pups/No. of live pups
Live birth index (%) = (No. of liveborn pups/Total No. of pups born) × 100
Offspring viability indices
Viability index (%) = (No. of surviving pus on day 4 after birth/No. of liveborn pups on day 0 after birth)
× 100

Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
Organ weight findings including organ / body weight ratios
no effects observed
Description (incidence and severity)(on reproductive organs)
Gross pathological findings
no effects observed
Description (incidence and severity)(on reproductive organs)
Histopathological findings: non-neoplastic
no effects observed
Description (incidence and severity)(on reproductive organs)

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

Effect levels (P0)28Key result
false
Dose descriptor
NOAEL
Effect level600

mg/kg bw/day (actual dose received)

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
Sexual maturation
not examined
Organ weight findings including organ / body weight ratios
not examined
Gross pathological findings
no effects observed
Histopathological findings
no effects observed

Effect levels (F1)
Key result
false
Dose descriptor
NOAEL
Generation
F1
Effect level600

mg/kg bw/day (actual dose received)29

Sex
male/female
Basis for effect level
other: No effects on development

Overall reproductive toxicity
Key result
false
Reproductive effects observed
not specified

Any other information on results incl. tables
Field content is not in a valid XML format and thus ignored!

Applicant's summary and conclusion
Conclusions
NOAEL for the rat reproductive/developmental toxicity of 1-propene, tetramer was determined to be
600 mg/kg bw/day, the highest dose tested.
Executive summary
In the combined repeated oral dose toxicity study (0, 40, 150, and 600 mg/kg bw/day) with thereproduction/developmental toxicity screening test (OECD TG 422), no effects of this substance on
reproductive and developmental parameters were observed at 600 mg/kg bw/day. NOAEL for the rat
reproductive/developmental toxicity of 1-propene, tetramer was determined to be 600 mg/kg bw/day,the highest dose tested.

30

DOMAIN
Substance
SUBSTANCE: 1-propene, tetramer
UUID: IUC5-e0ca2a88-57ae-44ba-bb7f-0f74fba1efe5
Dossier UUID:
Author:Date: 2022-12-16T16:15:56.420+09:00
Remarks:
Substance name1-propene, tetramer
Legal entity
National Institute of Health Sciences / Kawasaki / Japan

Identification of substance
Reference substance
1-propene, tetramer / 6842-15-5
EC number

EC name

CAS number

CAS name

6842-15-5
IUPAC nameRole in the supply chain
Manufacturer
false
Importer
false
Only representativefalse
Downstream user
false

31

References
Reference Substances
REFERENCE_SUBSTANCE: 1-propene, tetramer
UUID: IUC5-67a7f2be-af23-4a38-8ea7-67a5ffccffba
Dossier UUID:
Author:Date: 2017-10-30T11:27:04.000+09:00
Remarks:
Reference substance name1-propene, tetramer

Inventory
CAS number
6842-15-5

Molecular and structural information
Structural formula32

Test Materials
TEST_MATERIAL_INFORMATION: 1-Propene, tetramer
UUID: e334fdc6-f78b-3025-a4d2-f4c305496a6f
Dossier UUID:
Author:Date: 2022-12-15T10:52:15.792+09:00
Remarks:
Name
1-Propene, tetramer

Composition
Composition
Type
Constituent
Reference substance
1-propene, tetramer / 6842-15-5
EC number

EC name

CAS number

CAS name

6842-15-5
IUPAC name

Other characteristics
Details on test material
Name of test material (as cited in study report): 1-Propene, tetramer- Analytical purity: 99.9%- Lot/batch No.: MZ5G05-2- Storage condition of test material: at a cold place (temperature 2~6℃) in a light resistant container- Stability under test conditions: The stability of test material was identified by analysis of the remainder.

33

TEST_MATERIAL_INFORMATION: 1-Propene, tetramer
UUID: a7b2c6cb-5090-36bb-abb7-b59599e70713
Dossier UUID:
Author:Date: 2022-12-15T10:40:41.973+09:00
Remarks:
Name
1-Propene, tetramer

Composition
Composition
Type
Constituent
Reference substance
1-propene, tetramer / 6842-15-5
EC number

EC name

CAS number

CAS name

6842-15-5
IUPAC name

Other characteristics
Details on test material
Name of test material (as cited in study report): Propylenetetramer- Analytical purity: 99.9%- Lot/batch No.: C6UE654- Storage condition of test material: at a cold place (temperature 2~10 ℃) in a light resistant container- Stability under test conditions: The stability of test material was identified by analysis of the remainder.

34

TEST_MATERIAL_INFORMATION: 1-Propene, tetramer
UUID: e1d877e3-561a-33ec-8363-d285fa00151a
Dossier UUID:
Author:Date: 2022-12-15T10:46:32.444+09:00
Remarks:
Name
1-Propene, tetramer

Composition
Composition
Type
Constituent
Reference substance
1-propene, tetramer / 6842-15-5
EC number

EC name

CAS number

CAS name

6842-15-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 1-Propene, tetramer- Analytical purity: 71.2% for (C3H6)4- Supplier: Nippon Oil Corporation- Lot/batch No.: MZ5A01- Storage condition of test material: under room temperature, closed container

35

TEST_MATERIAL_INFORMATION: 1-Propene, tetramer
UUID: d25d1671-4d65-3bad-8e32-fbb280dac1a4
Dossier UUID:
Author:Date: 2022-12-15T10:44:40.336+09:00
Remarks:
Name
1-Propene, tetramer

Composition
Composition
Type
Constituent
Reference substance
1-propene, tetramer / 6842-15-5
EC number

EC name

CAS number

CAS name

6842-15-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 1-Propene, tetramer- Purity: 99.9%- Lot/batch No.: MZ5G05-2- Storage condition of test material: Refrigeration- Stability under test conditions: The stability of test material was identified by analysis of the remainder.

36

Literatures
LITERATURE: Combined repeat dose and reproductive/
developmental toxicity screening test of 1-Propene,
tetramer by oral administration in rats
UUID: 660d1cf9-7876-3bf6-9119-c6d011caddd7
Dossier UUID:
Author:Date: 2017-02-15T15:56:31.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Combined repeat dose and reproductive/developmental toxicity screening test of 1-Propene, tetramer
by oral administration in rats
Author
MHLW, Japan
Year
2013
Bibliographic source
available in the web of Japan Existing Chemical Data Base (JECDB) at http://dra4.nihs.go.jp/
mhlw_data/jsp/SearchPageENG.jsp
Testing facility
Safety Research Institute for Chemical Compounds Co., Ltd.

37

LITERATURE: In Vitro Chromosomal Aberration Test of 1Propene, tetramer on Cultured Chinese Hamster Cells.
UUID: 17074494-e98d-3b6c-b658-4c47fbe425cd
Dossier UUID:
Author:Date: 2017-02-15T15:59:26.000+09:00
Remarks:

General information
Reference Typestudy report
Title
In Vitro Chromosomal Aberration Test of 1-Propene, tetramer on Cultured Chinese Hamster Cells.
Author
MHLW, Japan
Year
2006
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
BoZo Research Center

38

LITERATURE: Reverse Mutation Test of 1-Propene,
tetramer on Bacteria.
UUID: 9cab12b7-5381-3ef6-9a60-ca82a090a84a
Dossier UUID:
Author:Date: 2017-02-15T15:58:12.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Reverse Mutation Test of 1-Propene, tetramer on Bacteria.
Author
MHLW, Japan
Year
2006
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
Research Institute for Animal Science in Biochemistry & Toxicology (RIAS)

39

LITERATURE: Single Dose Oral Toxicity Test of 1Propene, tetramer in RatsUUID: 5da23c5a-577c-376b-9ef5-ad3683ba9b5aDossier UUID:
Author:Date: 2017-02-15T15:52:21.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Single Dose Oral Toxicity Test of 1-Propene, tetramer in Rats
Author
MHLW, Japan
Year
2006
Bibliographic source
available in the web of Japan Existing Chemical Data Base (JECDB) at http://dra4.nihs.go.jp/
mhlw_data/jsp/SearchPageENG.jsp
Testing facility
Research Institute for Animal Science in Biochemistry and Toxicology.

40

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 systemIUCLID441

ID
16558402024DIV750

42