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Printing Date
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2017-01-04 16:26:52 JST
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Restriction of specific regulatory purposes
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Confidentiality
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Name
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4-chlorobenzoyl chloride
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Legal entity owner
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National Institute of Health Sciences / Tokyo / Japan
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UUID
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IUC5-87ac8376-058e-4153-acc0-e69617beb555
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Dossier UUID
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0
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Author
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dra / National Institute of Health Sciences / Tokyo / Japan
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Date
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2017-01-04 16:25:23 JST
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Remarks
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Chemical name
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4-chlorobenzoyl chloride
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Legal entity
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UUID
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IUC5-a979f21c-55c9-4b3c-9783-184bbe71d749
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Dossier UUID
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0
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Author
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dra / National Institute of Health Sciences / Tokyo / Japan
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Date
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2017-01-04 16:17:31 JST
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Remarks
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Purpose flag
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key study
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Study result type
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experimental result
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Reliability
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1 (reliable without restriction)
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Rationale for reliability incl. deficiencies
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OECD Test Guideline study under GLP condition
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Reference type
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Author
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Year
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Title
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Bibliographic source
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Testing laboratory
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Report no.
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Owner company
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Company study no.
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Report date
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study report
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MHW (Ministry of Health and Welfare), Japan
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2007
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Single Dose Oral Toxicity Test of 4-chlorobenzoyl chloride in Rats
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Japan Existing Chemical Data Base (JECDB)
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Biosafety Research Center, Foods, Drugs and Pesticides (An-Pyo Center)
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data published
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acute toxic class method
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yes
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Qualifier
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Guideline
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Deviations
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according to
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OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
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no
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yes
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yes
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Identifier
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Identity
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CAS number
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1220-01-0
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- 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, and insoluble 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 |
rat
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Crj: CD(SD)
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female
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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 |
oral: gavage
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corn oil
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VEHICLE
- Concentration in vehicle: 40 w/v% - Lot no.: V4F1900 produced by Nacalai Tesque, INC.. MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw |
2000 mg/kg bw
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First time of administration: 3 females (animal ID No. 3, 7, 10) /dose
Second time of administration: 3 females (animal ID No. 6, 8, 9)/dose |
no
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- 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 were observed in the first administration, therefore the second dose was also set as 2000 mg/kg bw |
No
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Sex
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Endpoint
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Effect level
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Based on
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95% CL
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Remarks
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female
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LD50
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> 2000 mg/kg bw
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act. ingr.
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No deaths were observed in first and second times.
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No changes related to the test substance were observed in first and second times.
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No changes related to the test substance were observed in first and second times.
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No changes related to the test substance were observed in first and second times.
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- Organ weights: No data
- Histopathology: No data - Potential target organs: Not identified - Other observations: No data |
The LD50 value was more than 2000 mg/kg bw for female rats.
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UUID
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IUC5-2c9bcc31-9c27-489b-aab9-4ae7f1fdf45c
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Dossier UUID
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0
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Author
|
dra / National Institute of Health Sciences / Tokyo / Japan
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Date
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2017-01-04 16:26:31 JST
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Remarks
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Purpose flag
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key study
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Study result type
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experimental result
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Reliability
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1 (reliable without restriction)
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Rationale for reliability incl. deficiencies
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OECD Test Guideline study under GLP condition
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Reference type
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Author
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Year
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Title
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Bibliographic source
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Testing laboratory
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Report no.
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Owner company
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Company study no.
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Report date
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study report
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MHW (Ministry of Health and Welfare), Japan
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2011
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A combined repeated-dose/reproductive-developmental toxicity study of 4-chlorobenzoyl chloride by oral administration in rats.
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Japan Existing Chemical Data Base (JECDB)
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BoZo Research Center Inc.
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data published
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7.8.1 Toxicity to reproduction: Toxicity to reproduction.001
7.8.2 Developmental toxicity/teratogenicity: Developmental toxicity/teratogenicity.001 |
combined repeated dose and reproduction / developmental screening
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no
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Qualifier
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Guideline
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Deviations
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according to
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OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
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no
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yes
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yes
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Identifier
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Identity
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CAS number
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122-01-0
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- 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, and insoluble 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 |
rat
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Crj: CD(SD)
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male/female
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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 |
oral: gavage
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corn oil
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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 |
yes
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Test suspensions at each concentration to be used for males in week 1 and six week of administration were analyzed by the HPLC method at Bozo Research Center Inc. Results showed that the concentration of the test article in each suspension was 98.0 to 104.0% of the nominal concentration and both values were within the acceptable range (concentration: percentage of the nominal concentration, 100 ± 10%; C.V.: 10% or below)
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(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
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Daily: 7 times / week
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0 (vehicle), 20, 100 and 500 mg/kg bw/day
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Basis
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actual ingested
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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 mating and examined after the administration period or after a 14 day recovery period. |
yes, concurrent vehicle
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- 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 was administered for 14 days. As a result, no death, and no effects of food consumption and hematology were observed in all treated groups. Loose stool, salivation, pale stool (females), slight depression of 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 the glandular in males were observed in the 500 mg/kg bw/day group. Raised focus in the forestomach 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.
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no
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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 lactation 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 of administration and on the day of necropsy, and males and females in the recovery groups were weighed on days 1, 4, 8, 11 and 14 of recovery and on the day of necropsy in addition to the measurement days for males in the main groups. Females in the main groups were weighed on days 1, 4, 8, 11 and 15 of administration (uncopulated animals were weighed on 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 administration, 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, platelet count, white blood cell count, differential white blood cell count, absolute number of each white blood cell, prothrombin time, activated partial thromboplastin time, fibrinogen CLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: 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, blood urea 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) - 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, followed 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, sediment, urine volume (4-hour volume), osmotic pressure, urine volume (20-hour volume), water intake (24-hour volume) BLOOD HORMONE: Yes - Time schedule for collection of serum: Same as clinical chemistry - 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 groups were examined in the final week of administration (day 37 of administration), females in the main groups on day 4 of lactation (day 42 to day 44 of administration) after necropsy of F1 pups, and males 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 administration 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, backward walking, etc.) 2) Manipulative Test. Auditory response, approach response, touch response, tail pinch response, pupillary 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 was measured by a motor activity sensor for experimental animals NS-AS01 (NeuroScience, Inc). The measurement was conducted for 1 hour, and measured values at 10-minute intervals and from 0 to 60 minutes were collected. |
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 (including 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) |
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 heterogeneous data was analyzed by a Steel test. In the recovery test, these values of two groups were analyzed by F test and Student or Aspin-Welch t-test. Frequency data were analysed by Fisher test. Statistical significance was set at < 5% by two-sided
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Endpoint
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Effect level
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Based on
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Sex
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Basis for effect level / Remarks
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NOAEL
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100 mg/kg bw/day (actual dose received)
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act. ingr.
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male/female
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Effects of lesions in the kidneys and stomach of both sexes and the thymus of females at 500 mg/kg bw/day
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yes (No animal died in any group.Clinical signs: 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. )
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no effects
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no effects
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not examined
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no effects
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no effects
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no effects
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no effects (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.)
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no effects
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yes (see Details on results)
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yes (see Details on results)
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yes (see Details on results)
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not examined
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DETAILED CLINICAL OBSERVATIONS, MANIPULATIVE TEST, GRIP STRENGTH TEST AND LOCOMOTOR ACTIVITY MEASUREMENT:There were no changes in main males and females and satellite females 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 observed in 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. Atrophy of the thymus was observed in all mating females, including the control group; however, the incidence 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 histopathological changes tended to resolve after the 14 day recovery period. |
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 |
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.
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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) were administered 4-chlorobenzoyl chloride at 0, 20, 100, and 500 mg/kg bw/day. Males were dosed for 42 days, 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 4 of 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 mating and 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 kidney weight increased in males at 500 mg/kg bw/day. Histopathological examination revealed 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. Atrophy of the thymus was observed in all mating females, including the control group; however, the incidence 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 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. |
UUID
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IUC5-2e59c227-c537-4b93-b700-e6a72a4ec840
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Dossier UUID
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0
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Author
|
dra / National Institute of Health Sciences / Tokyo / Japan
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Date
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2017-01-04 16:18:22 JST
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Remarks
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Purpose flag
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key study
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Study result type
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experimental result
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Reliability
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1 (reliable without restriction)
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||
Rationale for reliability incl. deficiencies
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OECD Test Guideline study under GLP condition
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Reference type
|
Author
|
Year
|
Title
|
Bibliographic source
|
Testing laboratory
|
Report no.
|
Owner company
|
Company study no.
|
Report date
|
study report
|
MHW (Ministry of Health and Welfare), Japan
|
2006
|
Reverse Mutation Test of 4-chlorobenzoyl chloride on Bacteria.
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Japan Existing Chemical Data Base (JECDB)
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Biosafety Research Center, Foods, Drugs and Pesticides (Anpyo Center)
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data published
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gene mutation
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bacterial reverse mutation assay (e.g. Ames test)
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Qualifier
|
Guideline
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Deviations
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according to
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OECD Guideline 471 (Bacterial Reverse Mutation Assay)
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no
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according to
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OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
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no
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according to
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JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
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no
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yes
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Identifier
|
Identity
|
CAS number
|
120-01-0
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- 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, and insoluble 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 |
Species/strain
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S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
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Metabolic activation
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with and without
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Metabolic activation system
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rat liver, induced by phenobarbital and 5,6-benzoflavone
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Species/strain
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E. coli WP2 uvr A
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Metabolic activation
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with and without
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Metabolic activation system
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rat liver, induced by phenobarbital and 5,6-benzoflavone
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-S9 mix: 7.81, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (TA100, TA1535, TA98 strains)
, 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(s)/solvent(s) used: Acetone
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Negative controls
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no
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Solvent / vehicle controls
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yes
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True negative controls
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no
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Positive controls
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yes
|
|
Positive control substance
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|
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 |
In any strain(s) tested with or without S9 mix, when the mean number of revertant colonies per plate increased twice more than that of the negative control and when the increase was shown to be dose-related and reproducible, the chemical was judged mutagenic.
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No
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Species/strain
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S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
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Metabolic activation
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with and without
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Test system
|
all strains/cell types tested
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Genotoxicity
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negative
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Cytotoxicity
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no
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Vehicle controls valid
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yes
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Negative controls valid
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not examined
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Positive controls valid
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yes
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Species/strain
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E. coli WP2 uvr A
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Metabolic activation
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with and without
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Test system
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all strains/cell types tested
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Genotoxicity
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negative
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Cytotoxicity
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no
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Vehicle controls valid
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yes
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Negative controls valid
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not examined
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Positive controls valid
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yes
|
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 |
negative
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In a bacterial reverse mutation assay using Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA (OECD TG 471), 4-chlorobenzoyl chloride was negative with or without metabolic activation.
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UUID
|
IUC5-1cc6257a-ecfb-4760-896a-031e4df5890e
|
|
Dossier UUID
|
0
|
|
Author
|
dra / National Institute of Health Sciences / Tokyo / Japan
|
|
Date
|
2017-01-04 16:18:26 JST
|
|
Remarks
|
Purpose flag
|
key study
|
||
Study result type
|
experimental result
|
||
Reliability
|
1 (reliable without restriction)
|
||
Rationale for reliability incl. deficiencies
|
OECD Test Guideline study under GLP condition
|
Reference type
|
Author
|
Year
|
Title
|
Bibliographic source
|
Testing laboratory
|
Report no.
|
Owner company
|
Company study no.
|
Report date
|
study report
|
MHW (Ministry of Health and Welfare), Japan
|
2006
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In Vitro Chromosomal Aberration Test of 4-chlorobenzoyl chloride on Cultured Chinese Hamster Cells.
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Japan Existing Chemical Data Base (JECDB)
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Biosafety Research Center, Foods, Drugs and Pesticides (Anpyo Center)
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data published
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chromosome aberration
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in vitro mammalian chromosome aberration test
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Qualifier
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Guideline
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Deviations
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according to
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OECD Guideline 473 (In vitro Mammalian Chromosome Aberration Test)
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no
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according to
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JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
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no
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yes
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yes
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Identifier
|
Identity
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CAS number
|
120-01-0
|
- 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, and insoluble 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 |
Chromosome
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Species/strain
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other: Chinese hamster lung(CHL/IU) cells
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Metabolic activation
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with and without
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Metabolic activation system
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rat liver, induced by phenobarbital and 5,6-benzoflavone
|
-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(s)/solvent(s) used: Acetone
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Negative controls
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no
|
||
Solvent / vehicle controls
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yes
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||
True negative controls
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no
|
||
Positive controls
|
yes
|
||
Positive control substance
|
|
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 |
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.Appearance incidence of cell with chromosomal aberrations:Negative(-): less than 5%Equivocal(±): 5% or more, less than 10%Positive(+): 10% or more
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Fisher and Chochran-Armitage trend tests (one-sided test, P = 2.5%)
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Species/strain
|
other: Chinese hamster lung (CHL/IU) cells
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Metabolic activation
|
with and without
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Test system
|
all strains/cell types tested
|
Genotoxicity
|
negative
|
Cytotoxicity
|
no
|
Vehicle controls valid
|
yes
|
Negative controls valid
|
not examined
|
Positive controls valid
|
yes
|
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 |
negative
|
4-Chlorobenzoyl chloride did not induce chromosomal aberrations in cultured cells.
|
Anin vitrochromosomal aberration test using CHL/IU cells (OECD TG 473) was negative with or without metabolic activation. |
UUID
|
IUC5-425c2820-7a3b-4906-ba61-2f2048c78a20
|
|
Dossier UUID
|
0
|
|
Author
|
dra / National Institute of Health Sciences / Tokyo / Japan
|
|
Date
|
2017-01-04 16:18:44 JST
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|
Remarks
|
Purpose flag
|
key study
|
||
Study result type
|
experimental result
|
||
Reliability
|
1 (reliable without restriction)
|
||
Rationale for reliability incl. deficiencies
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OECD Test Guideline study under GLP condition
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Reference type
|
Author
|
Year
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Title
|
Bibliographic source
|
Testing laboratory
|
Report no.
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Owner company
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Company study no.
|
Report date
|
study report
|
MHW (Ministry of Health and Welfare), Japan
|
2011
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A combined repeated-dose/reproductive-developmental toxicity study of 4-chlorobenzoyl chloride by oral administration in rats.
|
Japan Existing Chemical Data Base (JECDB)
|
BoZo Research Center Inc.
|
data published
|
7.5.Repeated dose toxicity: oral: Repeated dose toxicity: oral.001
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screening
|
no
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Qualifier
|
Guideline
|
Deviations
|
according to
|
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
|
no
|
yes
|
yes
|
Identifier
|
Identity
|
CAS number
|
120-01-0
|
- 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, and insoluble 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 |
rat
|
Crj: CD(SD)
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male/female
|
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 |
oral: gavage
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corn oil
|
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 |
- 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] |
yes
|
Test suspensions at each concentration to be used for males in week 1 and six week of administration were analyzed by the HPLC method at Bozo Research Center Inc. Results showed that the concentration of the test article in each suspension was 98.0 to 104.0% of the nominal concentration and both values were within the acceptable range (concentration: percentage of the nominal concentration, 100 ± 10%; C.V.: 10% or below)
|
(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 |
Daily: 7 times / week
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0 (vehicle), 20, 100 and 500 mg/kg bw/day
|
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Basis
|
actual ingested
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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 mating and examined after the administration period or after a 14 day recovery period. |
yes, concurrent vehicle
|
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 lactation 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 of administration and on the day of necropsy, and males and females in the recovery groups were weighed on days 1, 4, 8, 11 and 14 of recovery and on the day of necropsy in addition to the measurement days for males in the main groups. Females in the main groups were weighed on days 1, 4, 8, 11 and 15 of administration (uncopulated animals were weighed on 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 administration, 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 |
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.
|
Parameters examined in P male parental generations: testes weight, epididymides weight
|
PARAMETERS EXAMINED:The following parameters were examined in F1 offspring: Number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, and weight gain.
GROSS EXAMINATION OF DEAD PUPS: Yes, for external and internal abnormalities. |
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 (including 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) |
SACRIFICE: The F1 pups were euthanized on PND 4 by exsanguination under ether anesthesia.
GROSS NECROPSY: Yes |
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 heterogeneous data was analyzed by a Steel test. In the recovery test, these values of two groups were analyzed by F test and Student or Aspin-Welch t-test. Frequency data were analysed by Fisher test. Statistical significance was set at < 5% by two-sided
|
) 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 |
Number of live pups on day 0 of lactationBirth index (%) = (Number of live pups on day 0/Number of implantation 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 |
Endpoint
|
Generation
|
Sex
|
Effect level
|
Based on
|
Basis for effect level / Remarks
|
NOAEL (reproduction)
|
P
|
male/female
|
500 mg/kg bw/day (actual dose received)
|
no effects on reproduction
|
|
NOAEL (development)
|
F1
|
male/female
|
100 mg/kg bw/day (actual dose received)
|
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
|
yes (see Details on results)
|
no effects
|
no effects
|
no effects
|
not examined
|
no effects
|
no effects
|
no effects (on reproductive organs)
|
no effects (on reproductive organs)
|
CLINICAL SIGNS AND MORTALITY: Mortality: No animal died in any group.Clinical signs: 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.
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 differences 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 receiving 500 mg/kg bw/day, which showed high value, however this change was determined the incidental effect. |
no effects
|
no effects
|
yes (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)
|
not examined
|
not examined
|
no effects
|
not examined
|
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.
|
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. |
UUID
|
IUC5-a2a9360b-d978-4902-b119-ef75ccfb7959
|
|
Dossier UUID
|
0
|
|
Author
|
dra / National Institute of Health Sciences / Tokyo / Japan
|
|
Date
|
2017-01-04 16:23:46 JST
|
|
Remarks
|
Reference substance name
|
4-chlorobenzoyl chloride
|
EC number
|
204-515-3
|
CAS number
|
122-01-0
|
EC name
|
4-chlorobenzoyl chloride
|
||
Molecular formula
|
C7H4Cl2O
|
CAS number
|
122-01-0
|
Molecular formula
|
C7H4Cl2O
|
UUID
|
IUC4-b036ff75-0f3c-323b-b200-ed5f46cf5101
|
|
Dossier UUID
|
0
|
|
Author
|
XML Transformation V4.0 Plug-In
|
|
Date
|
2011-06-23 11:55:01 JST
|
|
Remarks
|
Successfully migrated to IUCLID 5.5 format.
|
Legal entity name
|
National Institute of Health Sciences
|
Flags
|
IT system
|
ID
|
Remarks
|
LEO
|
10767
|
||
IUCLID4
|
16558402024DIV750
|
Address
|
1-18-1 kamiyoga
|
Address
|
Setagaya-ku
|
Postal code
|
158-8501
|
Town
|
Tokyo
|
Country
|
Japan
|
Organisation
|
National Institute of Health Sciences
|
Department
|
Division of Risk Assessment
|
Title
|
Dr.
|
First name
|
Akihiko
|
Last name
|
Hirose
|
Address
|
1-18-1 Kamiyoga
|
Address
|
Setagaya-ku
|
Postal code
|
158-8501
|
Town
|
Tokyo
|
Country
|
Japan
|