Name: COMPLETE / SUBSTANCE : 2,3,4,4&#39;-Tetrahydroxybenzophenone / 31127-54-5
Fri, 16 Dec 2022, 14:10:53+0900 /Legal entity owner: National Institute of Health Sciences
Printing date: 2022-12-16T14:10:53.832+09:00

iTable of Contents
0/0 ............................................................................................................................. 1
National Institute of Health Science ..................................................................... 2
2,3,4,4'-Tetrahydroxybenzophenone ...................................................................... 3
CORE .......................................................................................................... 3
1 General information .......................................................................... 3
1.10 Assessment approach (assessment entities) ......................... 3
Assessment approach (assessment entities) ........................ 3
OECD .......................................................................................................... 4
D Health Effects .................................................................................. 4
60 Acute toxicity: oral .................................................................. 4
Acute toxicity: oral.001 ........................................................ 4
67 Repeated dose toxicity: oral .................................................... 7
Repeated dose toxicity: oral.001 ........................................... 770 Genetic toxicity in vitro ......................................................... 15
Genetic toxicity in vitro.001 ................................................ 15
Genetic toxicity in vitro.002 ................................................ 1971 Genetic toxicity in vivo .......................................................... 23
Genetic toxicity in vivo.001 ................................................ 2373 Toxicity to reproduction ........................................................ 27
Reproductive/developmental toxicity.001 ............................ 27
DOMAIN .................................................................................................... 35
Substance ......................................................................................... 35
Substance ................................................................................ 35
References ................................................................................................................ 36
Reference Substances ...................................................................................... 36
2,3,4,4'-Tetrahydroxybenzophenone ............................................................ 36
Test Materials .................................................................................................. 37
31127-54-5 ................................................................................................ 37
31127-54-5 ................................................................................................ 3831127-54-5 ................................................................................................ 3931127-54-5 ................................................................................................ 4031127-54-5 ................................................................................................ 4131127-54-5 ................................................................................................ 42
Literatures ....................................................................................................... 43
Combined repeat dose and reproductive/developmental toxicity screening
test of 2,3,4,4'-Tetrahydroxybenzophenone by oral administration in rats ....... 43
In Vitro Chromosomal Aberration Test of 2,3,4,4'Tetrahydroxybenzophenone on Cultured Chinese Hamster Cells. .................. 44
Micronucleous test of 2,3,4,4'-Tetrahydroxybenzophenone on rat .................. 45
Reverse Mutation Test of 2,3,4,4'-Tetrahydroxybenzophenone on
Bacteria. ................................................................................................... 46
Single Dose Oral Toxicity Test of 2,3,4,4'-Tetrahydroxybenzophenone in
Rats .......................................................................................................... 47
Legal Entities ................................................................................................... 48
National Institute of Health Sciences .......................................................... 48

ii

DOSSIER:UUID: 0
Dossier UUID:
Author:Date: 2022-12-16T14:10:53.684+09:00
Remarks:

Dossier header
Dossier submission type
Name
Complete table of contents
Versioncore 7.0
Name (given by user)

Dossier subject
Dossier subject
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
Public nameSubmitting legal entity
National Institute of Health Science
Dossier creation date/time
Fri, 16 Dec 2022, 14:10:53+0900
Used in category

1

LEGAL_ENTITY: National Institute of Health
Science
UUID: f51e7b54-9211-4863-90ce-fcf8a155d647
Dossier UUID:
Author:Date: 2022-11-07T16:24:02.822+09:00
Remarks:

General information
Legal entity nameNational Institute of Health Science22,3,4,4'-Tetrahydroxybenzophenone
CORE
General information
Assessment approach (assessment entities)
FIXED_RECORD: Assessment approach

UUID: bc9d15fc-3315-3940-9209-9e5c93e95d21
Dossier UUID:
Author:Date: 2016-12-21T15:06:08.000+09:00
Remarks:3

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

UUID: IUC5-81f8cc24-0026-4622-bd2a-06850fde77f0
Dossier UUID:
Author:Date: 2022-12-16T14:03:18.624+09:00
Remarks:

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 2,3,4,4'-Tetrahydroxybenzophenone in Rats / MHLW / publication
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
4Guideline
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test material
Test material information
31127-54-5

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: 6 weeks old- Weight at study initiation: Females, 123-135 g- Fasting period before study: Approximately 16 hrs- Housing:1/cage- Diet (e.g. ad libitum): Ad libitum except fasting period for 16 hrs before administration to 6 hrs afteradministration- Water (e.g. ad libitum):Ad libitum- Acclimation period:7 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 23±3 ℃(actual temperature: 21-25℃)- Humidity (%):50 ± 20% (actual humidity: 40-59%)- Air changes (per hr): Approximately 10-15 times/hr- Photoperiod (hrs dark / hrs light):12 hrs light / 12 hrs dark

Administration / exposure
Route of administration
oral: gavage
Vehiclecorn oil
Details on oral exposure- Amount of vehicle (if gavage):10 ml/kg bw
Doses
2000 mg/kg bw
No. of animals per sex per dose
3 (1st step group) and 3 (2nd step group)
Control animals
no5

Details 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); once a day (from day 1day14)- Frequency of weighing : just before administration (day 0), and 1,3,7 and 14 day after administration- Necropsy of survivors performed: yes

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

mg/kg bw

Mortality
No deaths were observed in any group.
Clinical signs
other: No changes related to the test substance were observed in any group.
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/PDF31127 -54 -5a.pdf

Applicant's summary and conclusion
Executive summary
The acute oral median lethal dose (LD50) for 2,3,4,4'-tetrahydroxybenzophenone was established at >2,000 mg/kg bw in female rats on the basis of a study conducted according to the Organisation for
Economic Co-operation and Development Test Guideline (OECD TG) 423. The substance caused nodeaths or clinical signs of toxicity at 2,000 mg/kg bw.

6

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

UUID: IUC5-b49d0715-b5a9-4ebc-bed0-1f609412fd9f
Dossier UUID:
Author:Date: 2022-12-16T14:05:03.365+09:00
Remarks:

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: GLP guideline study
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 2,3,4,4'-Tetrahydroxy /MHLW, Japan / study report
Data accessdata published7

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
31127-54-5

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: 10 weeks- Weight at study initiation: Males: 335-391 g; Females: 202-249 g- Housing: Steel wire-mesh cage (250 mm x 350 mm x 200 mm )- Diet: ad libitum- Water: ad libitum- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 21-23- Humidity (%): 46-61- Air changes: 10-15 times / hr
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure
Route of administration
oral: gavage
8Vehiclecorn oil
Details on oral exposure
PREPARATION OF DOSING SOLUTIONS:VEHICLE- Amount of vehicle (if gavage): 5 mL/kg bw- Lot/batch no. (if required): SDE2487
Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating and mating periods, and thereafter 14 days (P) Femal
es: 42-55 days including 14 days pre-mating, mating and gestation periods, and the days until day 4 oflactation; satellite animals: 42 days.
Frequency of treatment
Once/day, 7days/week
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 100, 300, and 1000 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 1000 mg/kg bw/day as a satellite group (without mating)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 study: 14day repeated dose oral toxicity test (doses: 100, 300, and 1000 mg/kg bw/day). In the 14-day repeateddose oral toxicity test, abnormalities were observed in animals in the 1000 mg/kg bw/day group,
such as low values of body weight and food consumption an increase in liver weight. No effects wereobserved at 300 mg/kg bw/day. On the basis of these effects, a dose level of 1000 mg/kg was selected as the maximum dose expecting to induce the toxic changes, and then dose levels of 300 and
100 mg/kg bw/day were selected as a middle dose and a minimum dose levels, respectively, in accordance with a common ratio of approximately 3.
- Rationale for animal assignment (if not random): Body weight-balanced randomization- 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: once before the start of administration, 3 times/day during the administration
period, and once during the recovery period
DETAILED CLINICAL OBSERVATIONS: Yes
The functional observational battery testing (FOB) was performed on all animals. Among the mea
sures in the FOB, detailed clinical observations were made before the initiation of dosing. Thereafter,in males of the main groups, detailed clinical observations were made once a week. Also in females9

of the main groups, detailed clinical observations were made once a week in pre-mating and mating
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 andrecovery 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) & males and females (recovery group): Days 1, 4, 8,
11, 15, 22, 25, 29, 32, 36, 39, 42, and the day of necropsy (after ca. 16h-fasting) in dosing period
Males and females (recovery group): Days 1, 4, 8, 11, 14, and the day of necropsy (after ca. 16hfasting) in recovery period
Females (main group): Twice a week during the precopulation period (days 1, 4, 8, 11, and 15); gestati
on days 0, 4, 7, 11, 14, 17, and 20; lactation days 0 and 4; and the day of necropsy (after ca. 16 hfasting)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption: Yes
Males (main) & males and females (recovery group): Days 1, 4, 8, 11, 15, 32, 36, and 39 in dosing
periodMales and females (recovery group): Days 1, 4, 8, 11, and 14 in recovery period
Females (main group): Days 1, 4, 8, 11, and 15; gestation days 1, 4, 7, 11, 14, 17, and 20; lactation days
2 and 4
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 (ether)- Animals fasted: Yes, 16-20h- How many animals: 5 sex/dose/group- Parameters checked in table were examined.
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 (males only)- Time schedule for collection of urine: Day 36-37 in dosing period, day 8-9 in recovery period- Metabolism cages used for collection of urine: No data
- Animals fasted: fasting and only water at libitum (4h-urine), no fasting (20h-urine)
Sacrifice and pathology
GROSS PATHOLOGY: Yes, whole organs and tissues (see tables)
HISTOPATHOLOGY: Yes (see tables)
Other examinations
Organ weight: Brian, thyroids (including parathyroids), thymus, heart, liver, spleen, kidneys, adrenals,
testes, epididymis
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).
10

In the recovery test, these values of two groups were analyzed by F test. If variances were homogene
ous, 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
effects observed, treatment-related
Mortality
mortality observed, treatment-related
Body weight and weight changes
effects observed, treatment-related
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
Clinical biochemistry findings
effects observed, treatment-related
Urinalysis findings
effects observed, treatment-related
Behaviour (functional findings)
effects observed, treatment-related
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
CLINICAL SIGNS AND MORTALITY
Males: No dead or moribund animals were observed. Salivation was observed at 1000 mg/kg bw/day.
11Females: After delivery (day 0 of lactation), one animal died at 1000 mg/kg bw/day.
Home cage observation: No effects.
In-the-hand observation: No effects.
Open field observation: No effects.
-Sensory motor reflexes:
Auditory response, approach response, touch response, tail pinch response, pupillary reflex, aerial
righting reflex: No effects. Landing foot splay: High value in females at 1000 mg/kg bw/day (maingroup, day 4 of lactation)-Forelimb and hindlimb grip strengths: Low value of hindlimb grip strength in males at 1000 mg/kg
bw/day in the 6-week of dosing-Motor activity: High value in females at 300 mg/kg bw/day (main group, day 4 of lactation) withoutdose-response relationship. In females, high value at 1000 mg/kg bw/day in the 6-week of dosing in
the recovery group, but not in the main group at the same dose. (No toxicological effects)
BODY WEIGHT AND WEIGHT GAIN
Males: Low values of body weight gain was observed at 1000 mg/kg bw/day in main group.
Females: Low value of body weight gain was observed at 1000 mg/kg bw/day at the ends of pre-mat
ing and gestation periods. Low value of body weight was observed at 300 mg/kg bw/day on day 4 oflactation.
At the end of recovery period, high value of body weight gain was observed in both sexes at 1000 mg/
kg bw/day.
FOOD CONSUMPTION
Males: Low value of food consumption was observed at 1000 mg/kg bw/day on day 4 of dosing, andsignificant increase was observed on days 36-42.
Females: Low value of food consumption was observed at 1000 mg/kg bw/day on day 4 of dosing,high value on day 15 of dosing, and then low value on day 20 of gestation and day 2 of lactation. Low
value of food consumption was observed at 300 mg/kg bw/day on day 4 of dosing and day 2 of lac
tation.
HAEMATOLOGY
Low values of RBC, Hb, Ht and MCHC, and high values of platelet, neutrophilic count and monocyte
count were observed at 1000 mg/kg bw/day at the end of dosing. At the end of recovery period, lowvalues of RBC and Hb, and high value of reticulocyte were observed in males at 1000 mg/kg bw/day.
Other significant findings in the table were within the normal ranges of physiological variability.
CLINICAL CHEMISTRYHigh value of inorganic phosphorus was observed at 300 mg/kg bw/day and more at the end of dos
ing. Other significant findings in the table were within the normal ranges of physiological variability.
URINALYSIS (only males; statistical analysis was not performed on qualitative items.)
Occult blood was observed in all administered males, and the degree of occult blood was enhanced in a dose-dependent manner. Dark yarrow color was observed in each 2-3 males at 100 mg/kg bw/day
and more.
ORGAN WEIGHTS
Low values of absolute and relative thymus weights were observed in females at 300 mg/kg bw/day
and more at the end of dosing. High value of relative liver weight was observed in both sexes at 1000
mg/kg bw/day at the end of dosing, and in females at the end of recovery period. Other significant fi
ndings in the table were within the normal ranges of physiological variability.
GROSS PATHOLOGY
In the dead female at 1000 mg/kg bw/day, small sizes of spleen and thymus were observed.
Undernourishment of general descriptions was observed in one female at 1000 mg/kg bw/day. Dark
discoloration of liver was observed in six males at 1000 mg/kg bw/day. Small size of thymus wasobserved in one female at 300 mg/kg bw/day, and in three females at 1000 mg/kg bw/day. Otherfindings in the table were considered to be incidental due to low frequency of appearance and/or pat
hological properties.

12

HISTOPATHOLOGY: NON-NEOPLASTIC
In the dead female at 1000 mg/kg bw/day, atrophy of white pup in the spleen and atrophy of thymus
were observed.
[At the end of dosing]
Cecum: Single cell necrosis of mucosal epithelial cells was observed in 4 males and 2 females at 100
mg/kg bw/day, in 3 males and 3 females at 300 mg/kg bw/day, and in 8 males and 7 females at 1000
mg/kg bw/day. Diffuse hyperplasia of mucosa was observed in 1 male and 1 female at 100 mg/kg
bw/day, in 3 males and 4 females at 300 mg/kg bw/day, and in 7 males and 6 females at 1000 mg/kg
bw/day.
Liver: Vacuolation of peripheral hepatocytes was dose-dependently decreased in males and females
at 300 mg/kg bw/day and more.
Thymus: Atrophy was dose-dependently increased in females at 300 mg/kg bw/day and more.
[At the end of recovery period]
Cecum: Diffuse hyperplasia of mucosa was observed in one male at 1000 mg/kg bw/day.
Other findings in the tables were considered to be incidental due to low frequency of appearance and/or pathological properties.

Effect levels
Key result
false
Dose descriptor
LOAEL
Effect level100

mg/kg bw/day (actual dose received)

Based ontest mat.
Sexmale/female
Basis for effect level
other: effects on the cecum

Target system / organ toxicity
Key result
false
Critical effects observed
not specified

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/PDF31127 -54 -5d.pdf

13

Applicant's summary and conclusion
Conclusions
Based on the effects on the cecum, the low observed adverse effect level (LOAEL) for repeated oral dosing was determined to be 100 mg/kg bw/day in male and female rats.
Executive summary
A combined repeated oral dose toxicity study with the reproduction/developmental toxicity screening
test was performed according to OECD TG 422. Male and female rats (12 animals/sex/dose) wereadministered 2,3,4,4'-tetrahydroxybenzophenone at 0, 100, 300, and 1,000 mg/kg bw/day. Males were
dosed for 42 days, including a 14-day pre-mating and mating periods; females were dosed for 41–45
days, including a 14-day pre-mating, mating, and gestation periods and the time until day 4 of lactation.
In addition, male and female rats (five animals/sex/dose) were administered 0 and 1,000 mg/kg bw/
day for 42 days without mating and examined after a 14-day recovery period. At 1,000 mg/kg bw/day,
one female died on day 0 of lactation, salivation was observed in males and a decreased body weightgain was observed in both sexes. Regarding hematology parameters, anemia was observed at the same
dose in males. Clinical chemistry studies demonstrated increased inorganic phosphorus at 300 mg/
kg bw/day and higher in males. In the thymus, decreased organ weight and atrophy were observed at
300 mg/kg bw/day and higher in females. In the cecum, single cell necrosis of mucosal epithelial cells
and diffuse mucosal hyperplasia were observed at 100 mg/kg bw/day and higher in both sexes. In theliver, in both sexes, increased organ weight at 1,000 mg/kg bw/day and decreased vacuolation of theperilobular hepatocytes in a dose-dependent manner at 300 mg/kg bw/day and higher was observed.
These changes tended to resolve after the recovery period. On the basis of the findings in the cecum,the LOAEL for repeated-dose toxicity of 2,3,4,4'-tetrahydroxybenzophenone was determined to be 100
mg/kg bw/day in male and female rats.

14

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

UUID: IUC5-9c9461e4-d1ec-4fcd-aa97-faf2ecde802a
Dossier UUID:
Author:Date: 2019-09-03T14:18:02.000+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 2,3,4,4'-Tetrahydroxybenzophenone 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
no15

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

Test material
Test material information
31127-54-5

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: 1.56, 3.13, 6.25, 12.5, 25, 50 μg/plate (TA1537, TA98 strains),
62.5, 125, 250, 500, 1000, 2000 μg/plate (WP2uvrA strain),and 31.3, 62.5, 125, 250, 500, 1000 μg/plate (TA100, TA1535 strains)+S9 mix: 15.6, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (all strains)
Vehicle / solvent- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substanceother: -S9 mix: 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA 100, TA98 and WP2 uvrA), sodium azide(TA1535) and 9-aminoacridine hydrochloride (TA1537). +S9 mix: 2-aminoanthracene (all strains)16

Details on test system and experimental conditions
RANGE-FINDING/SCREENING STUDIES:Concentration: 20-5000 μg/plate
Cytotoxic conc.: [-S9mix] Yes; >50 μg/plate (TA 98, TA1537), >1000 μg/plate (TA100, TA1535), >2000
μg/plate (WP2uvrA), [+S9mix] No.
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
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid
Key result
false
Species / strain
E. coli WP2 uvr A
bacteria
Metabolic activation
with and without
17

Genotoxicity
negative
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
validRemarks 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!

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, andTA1537 and Escherichia coli WP2uvrA (similar to OECD TG 471), 2,3,4,4'-tetrahydroxybenzophenone
was negative with or without metabolic activation.

18

ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.002

UUID: IUC5-22ba9be0-7295-4c58-9fdd-5b2112f052bb
Dossier UUID:
Author:Date: 2022-12-16T14:07:29.375+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 2,3,4,4'-Tetrahydroxybenzophenone on Cultured Chinese
Hamste / 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
Deviationsno
GLP compliance
yesType of assay
in vitro mammalian chromosome aberration test
chromosome aberration

Test material
Test material information
31127-54-5

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, 19.5, 39.1, 78.1, 156, 313 ug/mL+S9 mix (short-term treatment): 0, 39.1, 78.1, 156, 313, 625 ug/mL-S9 mix (continuous treatment, 24 h): 0, 19.5, 39.1, 78.1, 156, 313 ug/mL-S9 mix (continuous treatment, 48 h): 0, 2.44, 4.88, 9.77, 19.5, 39.1 ug/mL[Confirmation test]-S9 mix (short-term treatment): 0, 6.58, 9.88, 14.8, 22.2, 33.3, 50 ug/mL+S9 mix (short-term treatment): 0, 205, 256, 320, 400, 500 ug/mL
Vehicle / solvent- Vehicle(s)/solvent(s) used:DMSO
Controls
Untreated negative controlsno20

Negative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substancecyclophosphamide
mitomycin C
Details on test system and experimental conditions
METHOD OF APPLICATION: Exposure duration: [continuous treatment]: 24 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
positive weakly
Cytotoxicity / choice of top concentrations
cytotoxicity 625 ug/mL
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid

21

Key result
false
Species / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
cytotoxicity 313 ug/mL (short), 78.1 ug/mL and more (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/PDF31127 -54 -5f.pdf

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

22

Genetic toxicity in vivo
ENDPOINT_STUDY_RECORD: Genetic toxicity in vivo.001

UUID: IUC5-9f1cf02c-892b-4385-87b1-b9308a1b4173
Dossier UUID:
Author:Date: 2022-12-16T14:08:45.600+09:00
Remarks:

Administrative data
Endpoint
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus 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: GLP guideline study

Data source
Reference
Micronucleous test of 2,3,4,4'-Tetrahydroxybenzophenone on rat / MHLW Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
other: Japan (Iyakushin No.1604): Genetic toxicity test guideline of drugs
23

Deviations
not specified
Qualifieraccording to guideline
Guideline
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Deviations
not specified
GLP compliance
yesType of assay
micronucleus assay
chromosome aberration

Test material
Test material information
31127-54-5

Test animals
Speciesmouse
Strainother: CRLj:CD1(ICR)SPF
Sex
male
Details on test animals or test system and environmental conditions
TEST ANIMALS- Source: Charles River Laboratories Japan, Inc. Hino Farm
- Age at study initiation: 7 weeks old- Weight at study initiation: 29.6-34.4 g (avg. 31.9 g)- Assigned to test groups randomly: yes- Housing: polycarbonate cag (225 mm × 338 mm × 140 mm)- Diet: ad libitum- Water: ad libitum- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 22.8-24.1- Humidity (%):52.1-61.5- Air changes: 10-15/h- Photoperiod: 12 h dark/ 12 h light (light time: 7:00 to 19:00)

Administration / exposure
Route of administration
oral: gavage
24Vehicle- Vehicle(s)/solvent(s) used: corn oil- Lot/batch no. (if required): 6G2122
Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared on the day of administration by dissolving the test substance in cornoil.
Frequency of treatment
Twice, 24 h interval
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 125, 250, 500, 1000, 2000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose
6 animals/sex/doseControl animals
yes, concurrent vehicle
Positive control(s)mitomycin C- Route of administration: single intraperitoneal injection- Doses / concentrations: 2 mg/kg/day

Examinations
Tissues and cell types examined
Polychromatic erythrocytes from the femur bone marrow
Details of tissue and slide preparation
TREATMENT AND SAMPLING TIMES (in addition to information in specific fields): Cells for specimen
were collected 24 h after the last administration.
DETAILS OF SLIDE PREPARATION: Cell suspensions were expanded on the slides, fixed with methanol, and stained with Giemsa.
METHOD OF ANALYSIS: microscopy, blind method
Evaluation criteria
Criterion for determining a positive result: A dose-related increase in the number of micronucleatedcells.
Statistics
The number of micronucleated polychromatic erythrocytes was determined by the Kastenbaum andBowman method, and Cochran Armitage test;
Ratio of polychromatic erythrocytes to whole erythrocytes by F-test, and t-test.

Results and discussion
25

Test results
Key result
false
Sex
male
Genotoxicity
negative
Vehicle controls validity
valid
Negative controls validity
not examined
Positive controls validityvalid

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
Interpretation of results (migrated information): negative
The test substance did not produce micronuclei in the immature erythrocytes of the test species.
Executive summary
An in vivo micronucleus study (OECD TG 474) showed negative up to the limit dose (2,000 mg/kg bw/
day for 2 days) in mice.

26

Toxicity to reproduction
ENDPOINT_STUDY_RECORD: Reproductive/developmental toxicity.001

UUID: IUC5-bae76ab8-3928-4002-9f8e-b2f2b22173cc
Dossier UUID:
Author:Date: 2022-12-16T14:10:21.457+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: OECD Test Guideline study under GLP condition
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 2,3,4,4'-Tetrahydroxy /MHLW, Japan / study report
Data accessdata published

Materials and methods
27

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
31127-54-5

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: 10 weeks- Weight at study initiation: Males: 335-391 g; Females: 202-249 g- Housing: Steel wire-mesh cage (250 mm x 350 mm x 200 mm )- Diet: ad libitum- Water: ad libitum- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS- Temperature (°C): 21-23- Humidity (%): 46-61- Air changes: 10-15 times / hr
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure
Route of administration
oral: gavage
Vehiclecorn oil28

Details on exposure
PREPARATION OF DOSING SOLUTIONS:VEHICLE- Amount of vehicle (if gavage): 5 mL/kg bw- Lot/batch no. (if required): SDE2487
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 admi
nistration were analyzed by the HPLC method at Bozo Research Center Inc. Results showed thatthe concentration of the test article in each suspension was 95.7 to 104.5% of the nominal concen
tration and both values were within the acceptable range (concentration: percentage of the nominal c
oncentration, 100 ± 10%; C.V.: 10% or below)
Duration of treatment / exposure(P) Males: 42 days including 14 days pre-mating and mating periods, and thereafter 14 days(P) Females: 42-55 days including 14 days pre-mating, mating and gestation periods, and the days until day 4 of lactation; satellite animals: 42 days.
Frequency of treatment
Once/day, 7days/week
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 100, 300, and 1000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose
12 animals/sex/dose (main dose group), 5 males and 5 females at 0 and 1000 mg/kg bw/day as asatellite group (without mating).
Control animals
yes, concurrent vehicle

Examinations
Parental animals: Observations and examinations
CAGE SIDE OBSERVATIONS: Yes- Time schedule:
Males and females: once before the start of administration, 3 times/day during the administration
period, and once during the recovery period
DETAILED CLINICAL OBSERVATIONS: Yes
The functional observational battery testing (FOB) was performed on all animals. Among the mea
sures in the FOB, detailed clinical observations were made before the initiation of dosing. Thereafter,in males of the main groups, detailed clinical observations were made once a week. Also in females29

of the main groups, detailed clinical observations were made once a week in pre-mating and mating
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 andrecovery 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, 4, 8, 11, 15, 22, 25, 29, 32, 36,
39, 42, and the day of necropsy (after ca. 16h-fasting) in dosing period
Males and females (recovery group): Days 1, 4, 8, 11, 14, and the day of necropsy (after ca. 16h-fa
sting) in recovery period
Females (main group): Twice a week during the precopulation period (days 1, 4, 8, 11, and 15);
gestation days 0, 4, 7, 11, 14, 17, and 20; lactation days 0 and 4; and the day of necropsy (after ca. 16
h-fasting)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption: Yes
Males (main/recovery group): Days 1, 4, 8, 11, 15, 32, 36, and 39 in dosing period
Males and females (recovery group): Days 1, 4, 8, 11, and 14 in recovery period
Females (main group): Days 1, 4, 8, 11, and 15; gestation days 1, 4, 7, 11, 14, 17, and 20; lactation
days 2 and 4
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 (ether)- Animals fasted: Yes, 16-20h- How many animals: 5 sex/dose/group- Parameters checked in table were examined.
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 (males only)- Time schedule for collection of urine: Day 36-37 in dosing period, day 8-9 in recovery period- Metabolism cages used for collection of urine: No data
- Animals fasted: fasting and only water at libitum (4h-urine), no fasting (20h-urine)
NEUROBEHAVIOURAL EXAMINATION: No
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, epididymis weight
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.
30

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 last administration.
Maternal animals: Rats were euthanized by exsanguination under ether anesthesia on day 4 of lactati
on.
GROSS PATHOLOGY, Yes: whole organs and tissues
ORGAN WEIGHTS, Yes: Brain, thyroids(including parathyroids), thymus, heart, liver, spleen, kidneys,adrenals, testes, epididymis
HISTOPATHOLOGY, Yes: Cerebrum, cerebellum, pituitary gland, spinal cord (thoracic), sciatic nerve,
thyroid, parathyroid, adrenal glands, thymus, spleen, submandibular lymph nodes, mesenteric lymph
nodes, heart, lung (including the bronchi), stomach, duodenum, jejunum, ileum, cecum, colon, rectum,
liver, kidney, bladder, testis, epididymis, ovary, uterus, seminal vesicles, sternum and femur (includingbone marrows), macroscopic lesions.
Postmortem examinations (offspring)
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 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 homogene
ous, 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 co-housed animals) × 100
Fertility index (%) = (No. of pregnant females/No. of copulated females) × 100
Insemination index (%) = (No. of pregnant females/No. of copulated males) × 100
Duration of gestation (days) = day 0 of lactation – day 0 of gestation
Delivery index (%) = (No. of females delivered liveborn pups/No. of pregnant females) × 100
Implantation index (%) = (No. of implantation sites/No. of corpora lutea) × 100
Stillborn index (%) = (No. of stillborn pups/Total No. of pups born) × 100
Liveborn index (%) = (No. of liveborn pups/Total No. of pups born) × 100
External abnormalities (%) = (No. of pups with external abnormalities/No. of liveborn pups) × 100
Sex ratio = No. of liveborn male pups/(No. of liveborn male pups + No. of liveborn female pups)

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)
31

General toxicity (P0)
Clinical signs
effects observed, treatment-related
Description (incidence and severity)see 7.5.1 Repeated dose toxicity: oral.001
Body weight and weight changes
effects observed, treatment-related
Description (incidence and severity)see 7.5.1 Repeated dose toxicity: oral.001
Food consumption and compound intake (if feeding study)
effects observed, treatment-related
Description (incidence and severity)see 7.5.1 Repeated dose toxicity: oral.001
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 function: sperm measures
not examined
Reproductive performanceno effects observed
Description (incidence and severity)
on reproductive organs

Effect levels (P0)
Key result
false
Dose descriptor
NOAEL
32

Effect level1000

mg/kg bw/day (actual dose received)

Sexmale/female
Basis for effect level
other: no effects on reproduction
Key result
false
Dose descriptor
LOAEL
Effect level100

mg/kg bw/day (actual dose received)

Sexmale/female
Basis for effect level
other: (See repeated dose toxicity)

Results: F1 generation
General toxicity (F1)Clinical signs
no effects observed
Mortality / viability
no mortality observed
Body weight and weight changes
effects observed, treatment-related
Description (incidence and severity)
Low values of body weights of male and female pups were observed on postnatal day (PND) 4 at 300
mg/kg bw/day, and on PND 0 and PND 4 at 1000 mg/kg bw/day.
Sexual maturation
not examined
Organ weight findings including organ / body weight ratios
not examined
Gross pathological findings
no effects observed
Histopathological findings
not examined

Effect levels (F1)33

Key result
false
Dose descriptor
NOAEL
Generation
F1
Effect level100

mg/kg bw/day (actual dose received)

Sexmale/female
Basis for effect level
other: Low body weight of pups at 300 mg/kg bw/day

Overall reproductive toxicity
Key result
false
Reproductive effects observed
not specified

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/PDF31127 -54 -5d.pdf

Applicant's summary and conclusion
Conclusions
The NOAELs for rat reproductive toxicity and developmental toxicity were determined to be 1000 mg/
kg bw/day and 100 mg/kg bw/day, respectively.

Executive summary
In the combined repeated oral dose toxicity study (0, 100, 300, and 1,000 mg/kg bw/day) withthe reproduction/developmental toxicity screening test (OECD TG 422), no effects were found on
reproductive parameters up to 1,000 mg/kg bw/day. The body weights of male and female pups
decreased on postnatal day (PND) 4 at 300 mg/kg bw/day and higher, with decreased body weights
observed for both sexes on PND 0 at 1,000 mg/kg bw/day. The no observed adverse effect levels(NOAELs) for rat reproductive toxicity and developmental toxicity were determined to be 1,000 mg/kg
bw/day and 100 mg/kg bw/day, respectively.

34

DOMAIN
Substance
SUBSTANCE: 2,3,4,4'-Tetrahydroxybenzophenone
UUID: IUC5-240cac4f-f27d-4ed7-ab4d-9fde7ed35f68
Dossier UUID:
Author:Date: 2022-12-16T14:10:39.132+09:00
Remarks:
Substance name
2,3,4,4'-Tetrahydroxybenzophenone
Legal entity
National Institute of Health Sciences / Kawasaki / Japan

Identification of substance
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC nameRole in the supply chain
Manufacturer
false
Importer
false
Only representativefalse
Downstream user
false

35

References
Reference Substances
REFERENCE_SUBSTANCE: 2,3,4,4'Tetrahydroxybenzophenone
UUID: IUC5-9a63fecd-2bcb-4b40-abf4-b43e1c6090c7
Dossier UUID:
Author:Date: 2017-10-30T11:33:45.000+09:00
Remarks:
Reference substance name
2,3,4,4'-Tetrahydroxybenzophenone

Inventory
CAS number
31127-54-5

Molecular and structural information
Molecular formula
31127-54-5
Structural formula

36Test Materials
TEST_MATERIAL_INFORMATION: 31127-54-5
UUID: 93a10ff0-382e-3a77-a723-13aa1b58d75c
Dossier UUID:
Author:Date: 2017-02-15T16:04:12.000+09:00
Remarks:
Name
31127-54-5

Composition
Composition
Type
Constituent
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 2,3,4,4'-Tetrahydroxybenzophenone- Purity: 99.91%- Impurities (identity and concentrations): Unknown- Lot/batch No.: JSCXB- Stability under test conditions: Stable- Storage condition of test material: Refrigeration- Dosing solution storage condition: Room temperature and protected from light- Other: The dosing solution was used within 7 days of preparation.

37

TEST_MATERIAL_INFORMATION: 31127-54-5
UUID: 4c2d18df-3eef-3b53-b47a-180f8b7bb73d
Dossier UUID:
Author:Date: 2016-12-21T14:50:21.000+09:00
Remarks:
Name
31127-54-5

Composition
Composition
Type
Constituent
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 2,3,4,4'-Tetrahydroxybenzophenone- Purity: 100%
- Lot/batch No.: GL01
- Storage condition of test material: Refrigeration- Stability under test conditions: The stability of test material was identified by analysis of the remai
nder.

38

TEST_MATERIAL_INFORMATION: 31127-54-5
UUID: 465c97b2-bdb1-31f4-9ecd-14cf6ccceeb6
Dossier UUID:
Author:Date: 2017-02-15T16:07:17.000+09:00
Remarks:
Name
31127-54-5

Composition
Composition
Type
Constituent
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 2,3,4,4'-Tetrahydroxybenzophenone- Purity: 99.91%- Impurities (identity and concentrations): Unknown- Lot/batch No.: JSCXB- Stability under test conditions: Stable- Storage condition of test material: Refrigeration- Dosing solution storage condition: Room temperature and protected from light- Other: The dosing solution was used within 7 days of preparation.

39

TEST_MATERIAL_INFORMATION: 31127-54-5
UUID: 3ea7b465-3454-38a8-ad75-f19cc02fdb16
Dossier UUID:
Author:Date: 2017-02-15T16:02:42.000+09:00
Remarks:
Name
31127-54-5

Composition
Composition
Type
Constituent
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 2,3,4,4'-Tetrahydroxybenzophenone- Analytical purity: 99.86%- Lot/batch No.: GL01
- Stability under test conditions: The stability of test material was identified by analysis of the remainder.
- Storage condition of test material: At a cold place (temperature 2~8℃) in a light resistant container

40

TEST_MATERIAL_INFORMATION: 31127-54-5
UUID: bbbd9567-0515-3f86-b1a3-3e3d9795e741
Dossier UUID:
Author:Date: 2017-02-15T16:06:01.000+09:00
Remarks:
Name
31127-54-5

Composition
Composition
Type
Constituent
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 2,3,4,4'-Tetrahydroxybenzophenone- Analytical purity:99.9%- Lot/batch No.: EPF0296- Stability under test conditions: stable- Storage condition of test material: room temperature (17.6-20.8°C) in an airtight container.

41

TEST_MATERIAL_INFORMATION: 31127-54-5
UUID: 6beb221b-5dbc-3b58-8350-9527480efbca
Dossier UUID:
Author:Date: 2017-02-15T16:04:52.000+09:00
Remarks:
Name
31127-54-5

Composition
Composition
Type
Constituent
Reference substance
2,3,4,4'-Tetrahydroxybenzophenone / 31127-54-5
EC number

EC name

CAS number

CAS name

31127-54-5
IUPAC name

Other characteristics
Details on test material- Name of test material (as cited in study report): 2,3,4,4'-Tetrahydroxybenzophenone- Analytical purity: 99.86% (GL01), 99.91% (JSCXB)- Supplier: Tokyo Chemical Industry Co., Ltd- Lot/batch No.: GL01 and JSCXB- Storage condition of test material: cool and dark place

42

Literatures
LITERATURE: Combined repeat dose and reproductive/
developmental toxicity screening test of 2,3,4,4'Tetrahydroxybenzophenone by oral administration in rats
UUID: 7c3f72b1-27ef-3a47-99bc-11e3711427e3
Dossier UUID:
Author:Date: 2017-02-15T16:07:17.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Combined repeat dose and reproductive/developmental toxicity screening test of 2,3,4,4'-Tetrahydroxybenzophenone by oral administration in rats
Author
MHLW, Japan
Year
2009
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
BoZo Research Center

43

LITERATURE: In Vitro Chromosomal Aberration Test of
2,3,4,4'-Tetrahydroxybenzophenone on Cultured Chinese
Hamster Cells.
UUID: 4a1c80b0-857a-3d37-8c79-0685b9624cbf
Dossier UUID:
Author:Date: 2017-02-15T16:04:52.000+09:00
Remarks:

General information
Reference Typestudy report
Title
In Vitro Chromosomal Aberration Test of 2,3,4,4'-Tetrahydroxybenzophenone on Cultured Chinese
Hamster Cells.
Author
MHLW, Japan
Year
2007
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
BoZo Research Center

44

LITERATURE: Micronucleous test of 2,3,4,4'Tetrahydroxybenzophenone on rat
UUID: fec3c0ae-8118-3436-a32f-6c1913b31327
Dossier UUID:
Author:Date: 2017-02-15T16:06:01.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Micronucleous test of 2,3,4,4'-Tetrahydroxybenzophenone on rat
AuthorMHLW Japan
Bibliographic source
data unpublished
Testing facility
Chemicals Evaluation and Research Institute, Japan45

LITERATURE: Reverse Mutation Test of 2,3,4,4'Tetrahydroxybenzophenone on Bacteria.
UUID: dd1cb1c8-e2fe-385e-b2f4-51bdf223fc68
Dossier UUID:
Author:Date: 2016-12-21T14:50:21.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Reverse Mutation Test of 2,3,4,4'-Tetrahydroxybenzophenone 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)

46

LITERATURE: Single Dose Oral Toxicity Test of 2,3,4,4'Tetrahydroxybenzophenone in RatsUUID: fe4a0546-9397-369a-9114-737da6cca5e0
Dossier UUID:
Author:Date: 2017-02-15T16:02:42.000+09:00
Remarks:

General information
Reference Typepublication
Title
Single Dose Oral Toxicity Test of 2,3,4,4'-Tetrahydroxybenzophenone in Rats
Author
MHLW
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
BoZo Research Center47

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 systemIUCLID448

ID
16558402024DIV750

49