Name: COMPLETE / SUBSTANCE : 4-chlorobenzoyl chloride / 122-01-0 Fri, 16 Dec 2022,
15:00:52+0900 /Legal entity owner: National Institute of Health Sciences
Printing date: 2022-12-16T15:00:52.907+09:00

iTable of Contents
0/0 ............................................................................................................................. 1
National Institute of Health Science ..................................................................... 2
4-chlorobenzoyl chloride ...................................................................................... 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 ................................................ 21
73 Toxicity to reproduction ........................................................ 25
Toxicity to reproduction.001 ............................................... 25
DOMAIN .................................................................................................... 33
Substance ......................................................................................... 33
Substance ................................................................................ 33
References ................................................................................................................ 34
Reference Substances ...................................................................................... 34
4-chlorobenzoyl chloride ............................................................................ 34
Test Materials .................................................................................................. 35
4-chlorobenzoyl chloride ............................................................................ 35
4-chlorobenzoyl chloride ............................................................................ 36
4-chlorobenzoyl chloride ............................................................................ 37
4-chlorobenzoyl chloride ............................................................................ 38
4-chlorobenzoyl chloride ............................................................................ 39
Literatures ....................................................................................................... 40
A combined repeated-dose/reproductive-developmental toxicity study of 4chlorobenzoyl chloride by oral administration in rats. ................................... 40
In Vitro Chromosomal Aberration Test of 4-chlorobenzoyl chloride on
Cultured Chinese Hamster Cells. ................................................................ 41
Reverse Mutation Test of 4-chlorobenzoyl chloride on Bacteria. ................... 42
Single Dose Oral Toxicity Test of 4-chlorobenzoyl chloride in Rats ................ 43
Legal Entities ................................................................................................... 44
National Institute of Health Sciences .......................................................... 44ii

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4-chlorobenzoyl chloride / 122-01-0
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LEGAL_ENTITY: National Institute of Health
Science
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General information
Legal entity nameNational Institute of Health Science24-chlorobenzoyl chloride
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 4-chlorobenzoyl chloride in Rats / MHW (Ministry of Health andWelfare), 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)
Deviationsno
GLP compliance
yes
Test type
acute toxic class method
Limit test
yes

Test material
Test material information
4-chlorobenzoyl chloride

Test animals
Speciesratcommon species
Strain
Crj: CD(SD)rat
Sex
femaleDetails on test animals or test system and environmental conditions
TEST ANIMALS- Source: Charles River Japan Inc.
- Age at the time of purchase: 7 weeks old- Weight at dosing: Females, 190 - 198 g- Fasting period before study: Approximately 16 hrs- Housing: One animal/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: 7 - 8 days.
ENVIRONMENTAL CONDITIONS- Temperature (°C): 22.6 - 23.6
- Humidity (%): 45.6 - 62.2
- Ventilation (per hr): Approximately > 12 times- Photoperiod (hrs light / hrs dark): 12/12

Administration / exposure
Route of administration
oral: gavage
Vehiclecorn oil
Details on oral exposure
VEHICLE
5

- Concentration in vehicle: 40 w/v%
- Lot no.: V4F1900 produced by Nacalai Tesque, INC..
MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw
Doses
2000 mg/kg bw
No. of animals per sex per doseFirst time of administration: 3 females (animal ID No. 3, 7, 10) /dose
Second time of administration: 3 females (animal ID No. 6, 8, 9)/doseControl animals
noDetails on study design- Duration of observation period following administration: 14 days
- Frequency of observations: Day 1 (day of administration): within 30 minutes and 1, 2, 3, 4, 5 and 6 hrs
after administration. After day 2: once a day- Frequency of weighing: Days 1 (before administration), 7, and 14- Necropsy of survivors performed: Yes
The LD50 value was estimated to be around 820 mg / kg from information of the test substance.
Therefore, the starting administration dose was set as 2000 mg/kg bw. No clinical changes wereobserved in the first administration, therefore the second dose was also set as 2000 mg/kg bw
Statistics
No

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

mg/kg bw

Based onact. ingr.
Mortality
No deaths were observed in first and second times.
Clinical signs
other: No changes related to the test substance were observed in first and second times.
Gross pathology
No changes related to the test substance were observed in first and second times.
Other findings- Organ weights: No data6

- Histopathology: No data
- Potential target organs: Not identified- Other observations: No data

Applicant's summary and conclusion
Conclusions
The LD50 value was more than 2000 mg/kg bw for female rats.

7

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

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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: OECD Test Guideline study under GLP condition
Cross-reference
Reason / purpose for cross-reference
reference to same study
Remarks
7.8.1 Toxicity to reproduction: Toxicity to reproduction.001

Data source
Reference
A combined repeated-dose/reproductive-developmental toxicity study of 4-chlorobenzoyl chloride byor / MHW (Ministry of Health and Welfare), Japan / study report
Data accessdata published8

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

Test material
Test material information
4-chlorobenzoyl chloride

Test animals
Speciesratcommon rodent species
Strain
Crj: CD(SD)rat
Sexmale/female
Details on test animals or test system and environmental conditions
TEST ANIMALS- Source: Atsugi Breeding Center, Charles River Laboratories Japan, Inc.
- Age at study initiation:10 weeks of age- Weight at study initiation: 395-476 g for males and 225-282 g for females- Housing: bracket-type metallic wire-mesh cages (W 250 × D 350 × H 170 mm)- Diet (e.g. ad libitum):ad libitum- Water (e.g. ad libitum):ad libitum- Acclimation period:19 days
ENVIRONMENTAL CONDITIONS- Temperature (°C):21 to 24°C
- Humidity (%):40 to 56%- Air changes (per hr):10 to 15 times per hour
- Photoperiod (hrs dark / hrs light):12-hour lighting per day

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- Justification for use and choice of vehicle: No data
- Amount of vehicle (if gavage): 5 ml/kg bw- Lot/batch no. (if required): V0M3906 produced by Nacalai Tesque, INC.
- Dosing volume: 5 mL/kg bw- Stability (test solutions): At least 7 days
- Storage condition of test solution: Stored in a refrigerator
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 98.0 to 104.0% 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, mating, and thereafter 14 days (P)Females: 42–48
days including 14 days pre-mating, mating and gestation periods and the days until day 4 of lactation
Frequency of treatment
Daily: 7 times / week
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 20, 100 and 500 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose
12 animals/sex/dose (main dose group)
Five out of 12 males at 0 and 500 mg/kg bw/day were used as a recovery assessment group. In
addition, 10 females/dose were administered 0 and 500 mg/kg bw/day for 42 days without matingand examined after the administration period or after a 14 day recovery period.
Control animals
yes, concurrent vehicle
Details on study design- Dose selection rationale: A preliminary study was conducted to determine the doses to be employed.
Male and female rats were receiving 0, 250, 500, and 1000 mg/kg bw/day of the substance wasadministered for 14 days. As a result, no death, and no effects of food consumption and hematolog
y were observed in all treated groups. Loose stool, salivation, pale stool (females), slight depressionof body weights, increase in T-CHO, decrease in BUN (males) and increase in liver weight (females) were observed in both sexes receiving 1000 mg/kg. In addition, raised lesion in the forestomach
in both sexes and dark red colored lesion in the glandular in males were observed in the 1000 mg/
kg bw/day group. Raised focus in the forestomach in both sexes and dark red colored lesion in theglandular in males were observed in the 500 mg/kg bw/day group. Raised focus in the forestomach
10

in females was observed in the 250 mg/kg bw/day group. Therefore, the highest dose was set at 500
mg/kg bw/day, the concentration in which the expression of apparent toxicity is expected, and the
middle and low dose were set at 100 and 20 mg/kg bw/day using a common ratio of 5.
Positive controlnoExaminations
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- Time schedule:
Males: once before the start of administration, during the administration and recovery periods
Females: once before the start of administration, days 1, 7, 14 and 20 of gestation, and day 4 of lactati
on
BODY WEIGHT: Yes- Time schedule for examinations:
Males in the main groups were weighed on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39 and 42 ofadministration and on the day of necropsy, and males and females in the recovery groups were we
ighed on days 1, 4, 8, 11 and 14 of recovery and on the day of necropsy in addition to the measureme
nt days for males in the main groups.
Females in the main groups were weighed on days 1, 4, 8, 11 and 15 of administration (uncopulated
animals were weighed on day 18 and 22 of administration as well), days 0, 4, 7, 11, 14, 17 and 20 of
gestation, days 0 and 4 of lactation and the day of necropsy.
FOOD CONSUMPTION : Yes- Food consumption (g/day/rat) for each animal determined from the difference of the of the previous
day's feeding amount: Yes
Measurement of food consumption was conducted on all animals at the following frequencies:
males in the main groups on days 1, 4, 8, 11, 15, 32, 36, 39 and 42 of administration; males and females in the recovery groups on days 1, 4, 8, 11 and 14 of recovery in addition to the measurement
days for males in the main groups; and females in the main groups on days 1, 4, 8, 11 and 15 of admi
nistration, days 1, 4, 7, 11, 14, 17 and 20 of gestation and days 2 and 4 of lactation.
FOOD INTAKE: No
HAEMATOLOGY: Yes- Time schedule for collection of blood: On the day after the final day of administration and on the final
day of the recovery period- Anaesthetic used for blood collection: Yes (identity)- Animals fasted: Yes- How many animals:5 animals/sex/group- Parameters examined red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean
corpuscular hemoglobin, mean corpuscular hemoglobin concentration, reticulocyte percentage, plate
let count, white blood cell count, differential white blood cell count, absolute number of each whiteblood cell, prothrombin time, activated partial thromboplastin time, fibrinogen
CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: On the day after the final day of administration and on the final
day of the recovery period- Animals fasted: Yes- How many animals: 5 animals/sex/group- Parameters checked: ALP, total cholesterol, triglyceride, phospholipids, total bilirubin, glucose, bloodurea nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phosphorus, total protein,
albumin, A/G ratio, AST (GOT), ALT (GPT), LDH, γ-GTP
URINALYSIS: Yes- Time schedule for collection of urine: final week of administration (days 39 to 40 of administration)and in the final week of recovery (days 11 to 12 of recovery)11

- Metabolism cages used for collection of urine: Yes- Animals fasted: Yes ,A urine collector to collect four-hour urine samples under fasting but ad libitum drinking conditions, fo
llowed by collection of 20-hour urine samples under ad libitum feeding and drinking conditions.
- Parameters checked: pH, protein, ketones. glucose, occult blood, bilirubin, urobilinogen, color, sedim
ent, urine volume (4-hour volume), osmotic pressure, urine volume (20-hour volume), water intake (24hour volume)
BLOOD HORMONE: Yes- Time schedule for collection of serum: Same as clinical chemistry- Parameters checked: Triiodothyronine (T3), Thyroxin (T4), and thyroid stimulating hormone (THS) of
thyroid hormone
NEUROBEHAVIOURAL EXAMINATION: Yes- Time schedule for examinations: Manipulative test and measurements of grip strength and motor activity were conducted on 5 animals per group with the following frequencies: males in the main grou
ps were examined in the final week of administration (day 37 of administration), females in the maingroups on day 4 of lactation (day 42 to day 44 of administration) after necropsy of F1 pups, and ma
les and females in the recovery groups in the final week of administration (day 37 of administration)and in the final week of recovery (day 9 of recovery).
- Dose groups that were examined: All animals were examined for detailed clinical signs once before
the start of administration. Thereafter, males in the main groups were examined once weekly during
the administration period, whereas females were observed once weekly during the pre-mating adm
inistration period and mating period as well as on designated days during the gestation and lactation periods (days 1, 7, 14 and 20 of gestation, and day 4 of lactation). Animals in the recovery groups
were examined once weekly during the administration and recovery periods.
- Battery of functions tested:
1) Open field observation. Arousal, gait, posture, tremor, convulsion, rearing count, defecation (defecation count, urination), stereotypy (grooming, circling, etc.), abnormal behavior (self-biting, ba
ckward walking, etc.)
2) Manipulative Test. Auditory response, approach response, touch response, tail pinch response, p
upillary reflex, aerial righting reflex, landing foot splay
3) Measurement of Grip Strength. Following manipulative test, grip strength of forelimb and hind limb
was measured by CPU gauge MODEL-9502A (AIKOH Engineering Co., Ltd.).
4) Measurement of Motor Activity.Following measurement of grip strength, motor activity wasmeasured by a motor activity sensor for experimental animals NS-AS01 (NeuroScience, Inc). The mea
surement was conducted for 1 hour, and measured values at 10-minute intervals and from 0 to 60
minutes were collected.
Sacrifice and pathology
GROSS PATHOLOGY AND ORGAN WEIGHTS: Brain, puitality, thyroids(including parathyroids), thymus,
heart, liver, spleen, kidneys, adrenals, seminal, prostate, testes, epididymis, ovaries, uterus
HISTOPATHOLOGY: Cerebrum, cerebellum (including pontocerebellar), sciatic nerve, spinal cord
(thoracic), eye, optic nerve, Harder gland, pituitary, thyroid, parathyroid, adrenal glands, thymus, spleen, submandibular lymph nodes, mesenteric lymph nodes, heart, thoracic aorta, trachea, lung (includin
g bronchial), tongue, larynx, esophagus, stomach, duodenum, jejunum, ileum (including Peyer's patches), cecum, colon, rectum, submandibular gland, sublingual gland, liver, pancreas, kidney, bladder, testis, ovary, epididymis, uterus, vagina, prostate, seminal vesicles (including the coagulating gland),mammary gland (groin), sternum and femur (including bone marrows), femoral skeletal muscle, skin(groin), macroscopic lesions, and parts for identification (auricles)
Statistics
The data were analyzed for homogeneity of variance by the Bartlett test (level of significance: 0.01,
two-tailed). If variances were homogeneous, data was analyzed by the Dunnett test, whereas heterog
eneous data was analyzed by a Steel test. In the recovery test, these values of two groups were anal
yzed by F test and Student or Aspin-Welch t-test. Frequency data were analysed by Fisher test. Stati
stical significance was set at < 5% by two-sided

Results and discussion
12

Results of examinations
Clinical signs
effects observed, treatment-related
Description (incidence and severity)
Salivation was observed in 1 to 7 males receiving 500 mg/kg bw/day after Day 12 during the dosing
period. Salivation was observed in 1 mating female receiving 500 mg/kg bw/day after Day 12,
however this sign was not observed after Day 16 of gestation. No clinical signs were observed in both
sexes of recovery animals during the recovery period.
Mortality
no mortality observed
Body weight and weight changes
no effects observed
Food consumption and compound intake (if feeding study)no effects observed
Food efficiency
not examined
Ophthalmological findings
no effects observed
Haematological findings
no effects observed
Clinical biochemistry findings
no effects observed
Urinalysis findings
no effects observed
Description (incidence and severity)
Significant increases in water consumption and urine volume were observed in males receiving 500
mg/kg bw/day, but it was not considered to be toxicological effects. during the dosing period.
Behaviour (functional findings)
no effects observed
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Description (incidence and severity)
see Details on results
Gross pathological findings
effects observed, treatment-related
Description (incidence and severity)
see Details on results
Histopathological findings: non-neoplastic
effects observed, treatment-related
Description (incidence and severity)
see Details on results
Histopathological findings: neoplastic
not examined
13

Details on results
DETAILED CLINICAL OBSERVATIONS, MANIPULATIVE TEST, GRIP STRENGTH TEST AND LOCOMOTOR ACTIVITY MEASUREMENT:There were no changes in main males and females and satellite fem
ales during the dosing and recovery periods.
ORGAN WEIGHTS: An Increase in relative kidney weight was observed in males receiving 500 mg/kg
bw/day at the end of the administration period. Decreases in absolute and relative thymus weights
were observed in mating females receiving 500 mg/kg bw/day at the end of the administration. In
addition, a decrease in relative thyroid weight and increases in relative wights of the heart and testis
were observed in males and decreases in relative weights of the puitality and heart were observedin females at 500 mg/kg bw/day at end of the recovery period; however, these changes were determined to be within physiological variation range.
GROSS PATHOLOGY:
Kidneys: Irregular surface was observed in 1 male receiving 500 mg/kg bw/day.
Stomach: Thickening wall and focus/raised of forestomach was observed in both sexes receiving 500
mg/kg bw/day.
HISTOPATHOLOGY
basophilic changes in the tubular cells of kidneys from males and both mating and non-mating
females, and tubular dilatation, granular casts, and fibrosis was observed in male kidneys. Atrophyof the thymus was observed in all mating females, including the control group; however, the incide
nce was particularly high in the 500 mg/kg bw/day group. Furthermore, histopathological changes
were observed in the stomach, including intercellular edema in squamous cells and cell infiltration or
hyperplasia of the forestomach mucosa, in males and mating and non-mating females. Forestomach
erosion and ulceration were present in one mating female administered 500 mg/kg bw/day. These hi
stopathological changes tended to resolve after the 14 day recovery period.

Effect levels
Key result
false
Dose descriptor
NOAEL
Effect level100

mg/kg bw/day (actual dose received)

Based onact. ingr.
Sexmale/female
Basis for effect level
other: Effects of lesions in the kidneys and stomach of both sexes and the thymus of females at 500
mg/kg bw/day

Target system / organ toxicity
Key result
false
14

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/PDF122-01-0d.pdf

Applicant's summary and conclusion
Conclusions
Based on the effects of 4-chlorobenzoyl chloride on the thymus, kidney, and stomach, the no observed
adverse effect level (NOAEL) for repeated oral dosing was determined to be 100 mg/kg bw/day inmale and female rats.
Executive summary

A combined repeated oral dose toxicity study with the reproduction/developmental toxicity screening
test was performed according to the OECD TG 422. Male and female rats (12 animals/sex/dose) wereadministered 4-chlorobenzoyl chloride at 0, 20, 100, and 500 mg/kg bw/day. Males were dosed for 42days, including a 14 day pre-mating period and subsequent mating period; whereas females were dosed
for 42–48 days, including the 14 day pre-mating, mating, and gestation periods, and the time until day 4of lactation. Five out of 12 males at 0 and 500 mg/kg bw/day were used as a recovery assessment group.
In addition, 10 females/dose were administered 0 and 500 mg/kg bw/day for 42 days without matingand examined after the administration period or after a 14 day recovery period. At 500 mg/kg bw/day,the absolute and relative thymus weights had decreased in the mating group females. Relative kidneyweight increased in males at 500 mg/kg bw/day. Histopathological examination revealed basophilicchanges in the tubular cells of kidneys from males and both mating and non-mating females, andtubular dilatation, granular casts, and fibrosis was observed in male kidneys. Atrophy of the thymus wasobserved in all mating females, including the control group; however, the incidence was particularly highin the 500 mg/kg bw/day group. Furthermore, histopathological changes were observed in the stomach,including intercellular edema in squamous cells and cell infiltration or hyperplasia of the forestomachmucosa, in males and mating and non-mating females. Forestomach erosion and ulceration were
present in one mating female administered 500 mg/kg bw/day. These histopathological changes
tended to resolve after the 14 day recovery period. Based on the effects of 4-chlorobenzoyl chloride on
the thymus, kidney, and stomach, the no observed adverse effect level (NOAEL) for repeated oral dosing
was determined to be 100 mg/kg bw/day in male and female rats.

15

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

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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 4-chlorobenzoyl chloride on Bacteria. / MHW (Ministry of Health and Welfare),Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
16

in vitro gene mutation study in bacteria
Deviations
no
Qualifieraccording to guideline
Guideline
OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
in vitro gene mutation study in bacteria (before 21 July 1997)
Deviations
no
Qualifieraccording to guideline
Guideline
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviationsno
GLP compliance
yesType of assay
bacterial reverse mutation assay
in vitro gene mutation study in bacteria

Test material
Test material information
4-chlorobenzoyl chloride

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: 7.81, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (TA100, TA1535, TA98 strains)17

, 15.6, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (WP2uvrA strain), and 3.91, 7.81, 15.6, 31.3, 62.5, 125,
250 μg/plate (TA1537 strain)+S9 mix: 15.6, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (all strains)
Vehicle / solvent- Vehicle(s)/solvent(s) used: Acetone
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controlsnoPositive controls
yes
Positive control substanceother: other: -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)
Details on test system and experimental conditions
RANGE-FINDING/SCREENING STUDIES:Concentration: 9.19, 20.5, 51.2, 128, 320, 800, 2000, 5000 μg/
plate
Cytotoxic conc.: No
METHOD OF APPLICATION: Preincubation
DURATION- Preincubation period: 20 min at 37 ℃
- Exposure duration:48 hrs
NUMBER OF PLATES: 3
NUMBER OF REPLICATIONS: 1
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
18bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
valid
Key result
false
Species / strain
E. coli WP2 uvr A
bacteria
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
validRemarks on result
other: all strains/cell types tested Migrated from field 'Test system'.

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/PDF122-01-0e.pdf

Applicant's summary and conclusion
Conclusions
Interpretation of results (migrated information):19

negative
In a bacterial reverse mutation assay using Salmonella typhimurium TA100, TA1535, TA98, andTA1537, and Escherichia coli WP2uvrA (OECD TG 471), 4-chlorobenzoyl chloride was negative withor without metabolic activation.

20

ENDPOINT_STUDY_RECORD: Genetic toxicity in vitro.002

UUID: IUC5-1cc6257a-ecfb-4760-896a-031e4df5890e
Dossier UUID:
Author:Date: 2022-12-16T14:59:24.791+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 4-chlorobenzoyl chloride on Cultured Chinese Hamster Cells. /MHW (Ministry of Health and Welfare), Japan / study report
Data accessdata published

Materials and methods
Test guideline
Qualifieraccording to guideline
Guideline
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)in vitro cytogenicity / chromosome aberration study in mammalian cells
21

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
4-chlorobenzoyl chloride

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 (continuous treatment): 0, 74.1, 106, 151, 216, 309, 441 ug/mL-S9 mix (short-term treatment):
0, 106, 151, 216, 309, 441, 630 ug/mL+S9 mix (short-term treatment): 0, 106, 151, 216, 309, 441, 630,
900 ug/mL
Vehicle / solvent- Vehicle(s)/solvent(s) used: Acetone
Controls
Untreated negative controlsnoNegative solvent / vehicle controls
yes
True negative controlsno22

Positive 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
STAIN: Giemsa stain for 12 min.
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, which are usually used for chromosomal aberration testing with CHL, were employed.App
earance incidence of cell with chromosomal aberrations:Negative(-): less than 5%Equivocal(±): 5% or
more, less than 10%Positive(+): 10% or more
Statistics
Fisher and Chochran-Armitage trend tests (one-sided test, P = 2.5%)

Results and discussion
Test results
Key result
false
Species / strainother: Chinese hamster lung (CHL/IU) cells
Metabolic activation
with and without
Genotoxicity
negative
Cytotoxicity / choice of top concentrations
no cytotoxicity
Vehicle controls validity
valid
Untreated negative controls validity
not examined
Positive controls validity
validRemarks on result
other: all strains/cell types tested Migrated from field 'Test system'.

Any other information on results incl. tables
23

Figures and Tables (in English) are available in the following full report of the study.
http://dra4.nihs.go.jp/mhlw_data/home/pdf/PDF122-01-0f.pdf

Applicant's summary and conclusion
Conclusions
Interpretation of results (migrated information):negative
4-Chlorobenzoyl chloride did not induce chromosomal aberrations in cultured cells.
Executive summary
An in vitro chromosomal aberration test using CHL/IU cells (OECD TG 473) was negative with or without
metabolic activation.

24

Toxicity to reproduction
ENDPOINT_STUDY_RECORD: Toxicity to reproduction.001

UUID: IUC5-425c2820-7a3b-4906-ba61-2f2048c78a20
Dossier UUID:
Author:Date: 2022-12-16T15:00:22.648+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.Repeated dose toxicity: oral: Repeated dose toxicity: oral.001

Data source
Reference
A combined repeated-dose/reproductive-developmental toxicity study of 4-chlorobenzoyl chloride byor / MHW (Ministry of Health and Welfare), Japan / study report
Data accessdata published25

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

Test material
Test material information
4-chlorobenzoyl chloride

Test animals
Speciesrat
Strain
Crj: CD(SD)rat
Sexmale/female
Details on test animals or test system and environmental conditions
TEST ANIMALS- Source: Atsugi Breeding Center, Charles River Laboratories Japan, Inc.
- Age at study initiation:10 weeks of age- Weight at study initiation: 395-476 g for males and 225-282 g for females- Housing: bracket-type metallic wire-mesh cages (W 250 × D 350 × H 170 mm)- Diet (e.g. ad libitum):ad libitum- Water (e.g. ad libitum):ad libitum- Acclimation period:19 days
ENVIRONMENTAL CONDITIONS- Temperature (°C):21 to 24°C
- Humidity (%):40 to 56%- Air changes (per hr):10 to 15 times per hour
- Photoperiod (hrs dark / hrs light):12-hour lighting per day

Administration / exposure
Route of administration
oral: gavage
26

Vehiclecorn oil
Details on exposure
PREPARATION OF DOSING SOLUTIONS: Test substance was dissolved in corn oil for injection.
VEHICLE- Justification for use and choice of vehicle: No data
- Amount of vehicle (if gavage): 5 ml/kg bw- Lot/batch no. (if required): V0M3906 produced by Nacalai Tesque, INC.
- Dosing volume: 5 mL/kg bw- Stability (test solutions): At least 7 days
- Storage condition of test solution: Stored in a refrigerator
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- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no]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 98.0 to 104.0% 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, mating, and thereafter 14 days
(P)Females: 42-48 days including 14 days pre-mating, mating and gestation periods and the days unti
l day 4 of lactation
Frequency of treatment
Daily: 7 times / week
Doses / concentrations
Remarks
Doses / Concentrations:
0 (vehicle), 20, 100 and 500 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose
12 animals/sex/dose
Five out of 12 males at 0 and 500 mg/kg bw/day were used as a recovery assessment group. In
addition, 10 females/dose were administered 0 and 500 mg/kg bw/day for 42 days without matingand examined after the administration period or after a 14 day recovery period.
Control animals
yes, concurrent vehicle

Examinations
27

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- Time schedule:
Males: once before the start of administration, during the administration and recovery periods
Females: once before the start of administration, days 1, 7, 14 and 20 of gestation, and day 4 of lactati
on
BODY WEIGHT: Yes- Time schedule for examinations:
Males in the main groups were weighed on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39 and 42 ofadministration and on the day of necropsy, and males and females in the recovery groups were we
ighed on days 1, 4, 8, 11 and 14 of recovery and on the day of necropsy in addition to the measureme
nt days for males in the main groups.
Females in the main groups were weighed on days 1, 4, 8, 11 and 15 of administration (uncopulated
animals were weighed on day 18 and 22 of administration as well), days 0, 4, 7, 11, 14, 17 and 20 of
gestation, days 0 and 4 of lactation and the day of necropsy.
FOOD CONSUMPTION : Yes- Food consumption (g/day/rat) for each animal determined from the difference of the of the previous
day's feeding amount: Yes
Measurement of food consumption was conducted on all animals at the following frequencies:
males in the main groups on days 1, 4, 8, 11, 15, 32, 36, 39 and 42 of administration; males and females in the recovery groups on days 1, 4, 8, 11 and 14 of recovery in addition to the measurement
days for males in the main groups; and females in the main groups on days 1, 4, 8, 11 and 15 of admi
nistration, days 1, 4, 7, 11, 14, 17 and 20 of gestation and days 2 and 4 of lactation.
COMPOUND INTAKE: No
FOOD EFFICIENCY: No
WATER CONSUMPTION: 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, epididymides 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.
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 lactation.
GROSS PATHOLOGY AND ORGAN WEIGHTS：Yes Brain, puitality, thyroids(including parathyroids),
thymus, heart, liver, spleen, kidneys, adrenals, seminal, prostate, testes, epididymis, ovaries, uterus
HISTOPATHOLOGY: Yes Cerebrum, cerebellum (including pontocerebellar), sciatic nerve, spinal cord
(thoracic), eye, optic nerve, Harder gland, pituitary, thyroid, parathyroid, adrenal glands, thymus, spleen, submandibular lymph nodes, mesenteric lymph nodes, heart, thoracic aorta, trachea, lung (includin
g bronchial), tongue, larynx, esophagus, stomach, duodenum, jejunum, ileum (including Peyer's patches), cecum, colon, rectum, submandibular gland, sublingual gland, liver, pancreas, kidney, bladder, t28

estis, ovary, epididymis, uterus, vagina, prostate, seminal vesicles (including the coagulating gland),mammary gland (groin), sternum and femur (including bone marrows), femoral skeletal muscle, skin(groin), macroscopic lesions, and parts for identification (auricles)
Postmortem examinations (offspring)
SACRIFICE: The F1 pups were euthanized on PND 4 by exsanguination under ether anesthesia.
GROSS NECROPSY: Yes
Statistics
The data were analyzed for homogeneity of variance by the Bartlett test (level of significance: 0.01,
two-tailed). If variances were homogeneous, data was analyzed by the Dunnett test, whereas heterog
eneous data was analyzed by a Steel test. In the recovery test, these values of two groups were anal
yzed by F test and Student or Aspin-Welch t-test. Frequency data were analysed by Fisher test. Stati
stical significance was set at < 5% by 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 males/(No. of males + No. of females)
Viability index (%) = (No. of surviving pus on day 4 after birth/No. of liveborn pups on day 0 after birth)
× 100
Offspring viability indices
Number of live pups on day 0 of lactationBirth index (%) = (Number of live pups on day 0/Number of i
mplantation sites) ×100
Live birth index (%) = (Number of live pups on day 0/Number of pups born) ×100
Pups weight on day 0 of lactationSex ratio on day 0 of lactation
Number of live pups on day 4 of lactation
Pups weight on day 4 of lactation
Sex ratio on day 4 of lactation
Viability index = (Number of live pups on day 4 after birth/Number of live pups born) ×100

Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
Clinical signs
effects observed, treatment-related
Description (incidence and severity)
see Repeated dose toxicity: oral. 001
Mortality
no mortality observed
29

Body weight and weight changes
no effects observed
Food consumption and compound intake (if feeding study)no effects observed
Haematological findings
no effects observed
Clinical biochemistry findings
no effects observed
Urinalysis findings
no effects observed
Behaviour (functional findings)
no effects observed
Organ weight findings including organ / body weight ratios
effects observed, treatment-related
Description (incidence and severity)
see Repeated dose toxicity: oral. 001
Gross pathological findings
effects observed, treatment-related
Description (incidence and severity)
see Repeated dose toxicity: oral. 001
Histopathological findings: non-neoplastic
effects observed, treatment-related
Description (incidence and severity)
see Repeated dose toxicity: oral. 001

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

Details on results (P0)1) Estrous Cycle
There were no animals showing abnormal estrous cycles, and there were no significant differences in
the average length of the estrous cycle between the control group and any treatment groups.
2) Results of Mating
There were no significant differences in the number of elapsed days until copulation, copulation index,
insemination index or fertility index between the control group and any treatment groups.
3) Delivery Data and Delivery
With regard to delivery status, all pregnant animals delivered normally between day 21 and day 23
of gestation excluding one dam of 100 mg/kg bw/day group. There were no significant differences30

in the delivery index, duration of gestation, number of corpora lutea, number of implantation sites,
implantation index, stillborn index, number of liveborn pups or liveborn index between the control group and any treatment groups. Significantly increase of delivery index was observed in dam receivin
g 500 mg/kg bw/day, which showed high value, however this change was determined the incidental
effect.

Effect levels (P0)
Key result
false
Dose descriptor
NOAEL reproduction
Effect level500

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
effects observed, treatment-related
Description (incidence and severity)
The body weights of pups on postnatal day (PND) 0 and PND 4 were decreased in pups of both sexes
following 500 mg/kg bw/day dosing
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)31Key result
false
Dose descriptor
NOAEL development
Generation
F1
Effect level100

mg/kg bw/day (actual dose received)

Sexmale/female
Basis for effect level
other: The body weights of pups on postnatal day (PND) 0 and PND 4 were decreased in pups ofboth sexes following 500 mg/kg bw/day dosing

Overall reproductive toxicity
Key result
false
Reproductive effects observed
not specified

Applicant's summary and conclusion
Conclusions
The NOAELs for rat reproductive toxicity and developmental toxicity were determined to be 500 mg/
kg bw/day and 100 mg/kg bw/day, respectively.
Executive summary

In the combined repeated oral dose toxicity study with the reproduction/developmental toxicity
screening test (OECD TG 422), reproductive parameters were not affected up to 500 mg/kg bw/day.
The body weights of pups on postnatal day (PND) 0 and PND 4 were decreased in pups of both sexes
following 500 mg/kg bw/day dosing. The NOAELs for rat reproductive toxicity and developmental
toxicity were determined to be 500 mg/kg bw/day and 100 mg/kg bw/day, respectively.

32

DOMAIN
Substance
SUBSTANCE: 4-chlorobenzoyl chloride
UUID: IUC5-87ac8376-058e-4153-acc0-e69617beb555
Dossier UUID:
Author:Date: 2022-12-16T15:00:42.549+09:00
Remarks:
Substance name4-chlorobenzoyl chloride
Legal entity
National Institute of Health Sciences / Kawasaki / Japan

Identification of substance
Reference substance
4-chlorobenzoyl chloride / 122-01-0 / 204-515-3
EC number

EC name204-515-3

EC Inventory

CAS number

CAS name

122-01-0
IUPAC nameRole in the supply chain
Manufacturer
false
Importer
false
Only representativefalse
Downstream user
false

33

References
Reference Substances
REFERENCE_SUBSTANCE: 4-chlorobenzoyl chloride
UUID: IUC5-a2a9360b-d978-4902-b119-ef75ccfb7959
Dossier UUID:
Author:Date: 2017-01-04T16:23:46.000+09:00
Remarks:
Reference substance name4-chlorobenzoyl chloride

Inventory
Inventory number
Inventory name4-chlorobenzoyl chloride
Inventory
EC Inventory
Inventory number
204-515-3
CAS number
122-01-0
Molecular formula
C7H4Cl2O
Description
CAS number
122-01-0

Molecular and structural information
Molecular formula
C7H4Cl2O

34

Test Materials
TEST_MATERIAL_INFORMATION: 4-chlorobenzoyl
chloride
UUID: 3fa0a575-f847-3842-95a4-2f3f26e9dc93
Dossier UUID:
Author:Date: 2022-12-14T13:45:20.806+09:00
Remarks:
Name
4-chlorobenzoyl chloride

Composition
Other characteristics
Details on test material- Name of test material (as cited in study report): 4-chlorobenzoyl chloride- Molecular weight: 175.01- Physical state: Colorless liquid- Analytical purity: 99.79%- Melting point/ boiling point: 12—14°C/222°C-Solubility: Very soluble in acetone (656 mg/mL), methanol, ethanol, ether, ketone, and toluene, andinsoluble in water- Vapor pressure: 110°C /20 mmHg
- Specific gravity: 1.377/20°C- Odor: Very irritating odor
- Supplier: Iharanikkei Chemical Industry Co., Ltd- Lot/batch No.: I5001- Storage condition of test material: Room temperature

35

TEST_MATERIAL_INFORMATION: 4-chlorobenzoyl
chloride
UUID: 208c4aae-3a09-3923-bcf9-9345059a08a2
Dossier UUID:
Author:Date: 2022-12-14T13:46:16.567+09:00
Remarks:
Name
4-chlorobenzoyl chloride

Composition
Other characteristics
Details on test material- Name of test material (as cited in study report): 4-chlorobenzoyl chloride- Molecular weight: 175.01- Physical state: Colorless liquid to white crystal mass
- Analytical purity: 99.6%- Melting point/ boiling point: 12°C (solid point)/220-222°C-Flash point: 118°C- Solubility: Very soluble in acetone (656 mg/mL), methanol, ethanol, ether, ketone, and toluene, andinsoluble in water- Vapor pressure: 110°C /20 mmHg
- Specific gravity: 1.377/20°C- Odor: Very irritating odor
- Supplier: Iharanikkei Chemical Industry Co., Ltd- Lot/batch No.: KSSFK- Storage condition of test material: Room temperature

36

TEST_MATERIAL_INFORMATION: 4-chlorobenzoyl
chloride
UUID: c627e21d-6b77-3b99-a596-d268f2494fbe
Dossier UUID:
Author:Date: 2022-12-14T13:48:46.966+09:00
Remarks:
Name
4-chlorobenzoyl chloride

Composition
Other characteristics
Details on test material- Name of test material (as cited in study report): 4-chlorobenzoyl chloride- Molecular weight: 175.01- Physical state: Colorless liquid to white crystal mass
- Analytical purity: 99.6%- Melting point/ boiling point: 12°C (solid point)/220-222°C-Flash point: 118°C- Solubility: Very soluble in acetone (656 mg/mL), methanol, ethanol, ether, ketone, and toluene, andinsoluble in water- Vapor pressure: 110°C /20 mmHg
- Specific gravity: 1.377/20°C- Odor: Very irritating odor
- Supplier: Iharanikkei Chemical Industry Co., Ltd- Lot/batch No.: KSSFK- Storage condition of test material: Room temperature

37

TEST_MATERIAL_INFORMATION: 4-chlorobenzoyl
chloride
UUID: 50c7e013-2743-3358-848b-8b44357c2cb7
Dossier UUID:
Author:Date: 2022-12-14T13:47:32.636+09:00
Remarks:
Name
4-chlorobenzoyl chloride

Composition
Other characteristics
Details on test material- Name of test material (as cited in study report): 4-chlorobenzoyl chloride- Molecular weight: 175.01- Physical state: Colorless liquid- Analytical purity: 99.79%- Melting point/ boiling point: 12—14°C/222°C-Solubility: Very soluble in acetone (656 mg/mL), methanol, ethanol, ether, ketone, and toluene, andinsoluble in water- Vapor pressure: 110°C /20 mmHg
- Specific gravity: 1.377/20°C- Odor: Very irritating odor
- Supplier: Iharanikkei Chemical Industry Co., Ltd- Lot/batch No.: I5001- Storage condition of test material: Room temperature

38

TEST_MATERIAL_INFORMATION: 4-chlorobenzoyl
chloride
UUID: 53052755-25fd-308c-8792-dfa3751fafa4
Dossier UUID:
Author:Date: 2022-12-14T13:48:09.468+09:00
Remarks:
Name
4-chlorobenzoyl chloride

Composition
Other characteristics
Details on test material- Name of test material (as cited in study report): 4-chlorobenzoyl chloride- Molecular weight: 175.01- Physical state: Colorless liquid- Analytical purity: 99.79%- Melting point/ boiling point: 12—14°C/222°C-Solubility: Very soluble in acetone (656 mg/mL), methanol, ethanol, ether, ketone, and toluene, andinsoluble in water- Vapor pressure: 110°C /20 mmHg
- Specific gravity: 1.377/20°C- Odor: Very irritating odor
- Supplier: Iharanikkei Chemical Industry Co., Ltd- Lot/batch No.: I5001- Storage condition of test material: Room temperature

39

Literatures
LITERATURE: A combined repeated-dose/reproductivedevelopmental toxicity study of 4-chlorobenzoyl chloride
by oral administration in rats.
UUID: 9447876a-ad3b-3485-a963-3bae6a1ea3db
Dossier UUID:
Author:Date: 2022-12-14T14:00:48.127+09:00
Remarks:

General information
Reference Typestudy report
Title
A combined repeated-dose/reproductive-developmental toxicity study of 4-chlorobenzoyl chloride byoral administration in rats.
AuthorMHW (Ministry of Health and Welfare), Japan
Year
2011
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
BoZo Research Center Inc.
Study number
R-107240

LITERATURE: In Vitro Chromosomal Aberration Test of
4-chlorobenzoyl chloride on Cultured Chinese Hamster
Cells.
UUID: 93929503-6ac9-3c0b-b65a-e1c5433986f4
Dossier UUID:
Author:Date: 2017-01-04T16:18:26.000+09:00
Remarks:

General information
Reference Typestudy report
Title
In Vitro Chromosomal Aberration Test of 4-chlorobenzoyl chloride on Cultured Chinese Hamster
Cells.
AuthorMHW (Ministry of Health and Welfare), Japan
Year
2006
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
Biosafety Research Center, Foods, Drugs and Pesticides (Anpyo Center)41

LITERATURE: Reverse Mutation Test of 4-chlorobenzoyl
chloride on Bacteria.
UUID: 3291c047-b7ef-339b-be14-a659befe31ba
Dossier UUID:
Author:Date: 2017-01-04T16:18:22.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Reverse Mutation Test of 4-chlorobenzoyl chloride on Bacteria.
AuthorMHW (Ministry of Health and Welfare), Japan
Year
2006
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
Biosafety Research Center, Foods, Drugs and Pesticides (Anpyo Center)42

LITERATURE: Single Dose Oral Toxicity Test of 4chlorobenzoyl chloride in RatsUUID: 9bba3071-8e05-38a8-8af7-4bef22a4ff1a
Dossier UUID:
Author:Date: 2017-01-04T16:17:31.000+09:00
Remarks:

General information
Reference Typestudy report
Title
Single Dose Oral Toxicity Test of 4-chlorobenzoyl chloride in Rats
AuthorMHW (Ministry of Health and Welfare), Japan
Year
2007
Bibliographic source
Japan Existing Chemical Data Base (JECDB)
Testing facility
Biosafety Research Center, Foods, Drugs and Pesticides (An-Pyo Center)

43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 systemIUCLID444

ID
16558402024DIV750

45