4-chlorophenol

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

2005

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2007

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

Principles of method if other than guideline:

Remark: All schedules and examinations were performed in compliance with the Test Guideline ‘‘28 day repeated-dose toxicity study using mammals’’ of the Japanese Chemical Control Act (Official Name: Law Concerning the Examination and Regulation of Manufacture, etc. of Chemical Substances). This guideline is equivalent to OECD Test Guideline 407.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorophenol

EC Number:

203-402-6

EC Name:

4-chlorophenol

Cas Number:

106-48-9

Molecular formula:

C6H5ClO

IUPAC Name:

4-chlorophenol

Test animals

Species:

rat

Strain:

other: SPF [Crj:CD(SD)IGS]

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan Inc. (Kanagawa, Japan)
- Age at study initiation: 5–6 week
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2°
- Humidity (%): 55 ± 15
- Air changes (per hr): 10 times per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Test solutions were prepared at least once a week and were kept cool and in the dark until dosing. The stability was confirmed to be at least seven days under these conditions.

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
20 mg/kg bw/d
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
100 mg/kg bw/d
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
500 mg/kg bw/d
Basis:
actual ingested

No. of animals per sex per dose:

6 animals

Control animals:

yes

Details on study design:

- Dose selection rationale: Dose-finding study
- Rationale for selecting satellite groups: To measure pro-longing effects
- Post-exposure recovery period in satellite groups: Two weeks (sacrificed at 11 or 12 weeks of age)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- General behavior

DETAILED CLINICAL OBSERVATIONS: Yes
- Tremors
- Hypoactivity
- Abnormal gait

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes (Blood biochemistry)

URINALYSIS: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
- necropsy findings
- organ weights

HISTOPATHOLOGY: Yes
- Kidney
- Liver

Statistics:

- Quantitative data: Bartlett’s test (Bartlett 1937); homogeneity of distribution
- Recognized homogeneity: Dunnett’s test (Dunnett 1964); comparison between control and individual treatment groups.
- Not homogenous data: Steel’s multiple comparison test (Steel 1959) or the mean rank test of the Dunnett type (Hollander & Wolfe 1973).
- Qualitative data, e.g. histopathological findings: Mann–Whitney’s U-test (Mann & Whitney 1947) or Fisher’s exact test (Fisher 1973)

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS:
- Tremors, tachypnea and salivation were observed from five to 30 minutes after dosing in most animals in both sexes at 500 mg/kg bw/d.
- There were no other dose-dependent changes at any dose.

Effect levels

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Tremors, tachypnea and salivation.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

 

Toxicity findings for the test substance in young rat main study
Males	Dose [mg/kg bw/d]
	0	100	500
General behaviour
Tremors	0/12	0/6	12/12
Tachypnea	0/12	0/6	11/12
Salivation	0/12	0/6	9/12
Histopathology
Kidney	0/6	0/6	0/6
Liver	0/6	0/6	0/6
Data are numbers of animals with the change of the total examined.

 

Toxicity findings for the test substance in young rat main study
Females	Dose [mg/kg bw/d]
	0	100	500
General behaviour
Tremors	0/12	0/6	11/12
Tachypnea	0/12	0/6	9/12
Salivation	0/12	0/6	8/12
Histopathology
Kidney	0/6	0/6	0/6
Liver	0/6	0/6	0/6
Data are numbers of animals with the change of the total examined.