2-chlorophenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 - 31 Mar 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 Feb 1987

Deviations:

no

GLP compliance:

yes

Remarks:

according to Japanese GLP standard (as described on JECDB)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-chlorophenol

EC Number:

202-433-2

EC Name:

2-chlorophenol

Cas Number:

95-57-8

Molecular formula:

C6H5ClO

IUPAC Name:

2-chlorophenol

Test material form:

liquid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in a closed bottle at room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: water solubility is 2.71%, easy soluble in acetone and DMSO

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: dilution in olive oil

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

Crj:CD(SD)IGS

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc., Yokohama, Japan
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5 weeks
- Weight at study initiation: 128 - 139 g (males), 108 - 120 g (females)
- Fasting period before study: 18 h prior to administration until 3 h after administration
- Housing: 5 animals of the same sex per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 - 26
- Humidity (%): 45 - 63
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw
- Lot/batch no. (if required): 8123

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
In a pre-test, doses of 250, 500 and 1000 mg/kg bw was administered to 3 males and females. No mortality occured during the 7 day observation period. Based on this result, the main study was performed at 500, 1000 and 2000 mg/kg bw.

Doses:

500, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Remarks:

gavage with olive oil

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 5 times at the first day and daily thereafter. Individual weights were determined on Day 0 prior to administration and at Day 4, 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

Doses of 250, 500 and 1000 mg/kg bw were administered to 3 males and females. A control group was included. No death occurred during the following observation period (7 days). Locomotor activity was decreased in the high-dose group at the first day. According to this result, doses of 500, 1000 and 2000 mg/kg bw were applied in the main study.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no male died at 1000 mg/kg bw; 3/5 males died at 2000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/5 females died at 2000 mg/kg bw

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: combined approach: 5/10 animals died at 2000 mg/kg bw

Mortality:

500 mg/kg bw: 0/5 males and 0/5 females died
1000 mg/kg bw: 0/5 males and 0/5 females died
2000 mg/kg bw: 3/5 males and 2/5 females

Clinical signs:

500 and 1000 mg/kg bw: decreased locomotor activity, abnormal gait, clonic convulsion and lateral or prone position in males; decreased locomotor activity, abnormal gait and clonic convulsion in femals
2000 mg/kg bw: decreased locomotor activity and abnormal gait in males; abnormal gait in femals

all dose groups, non-surviving animals: decreased locomotor activity, clonic convulsion, lateral or prone position 15 minutes after administration

Body weight:

500 and 1000 mg/kg bw: body weight gains were within the normal ranges in males and females during the whole study period
2000 mg/kg bw: slightly decreased body weight gains observed in surviving animals at Day 4

Gross pathology:

500 and 1000 mg/kg bw: no abnormal findings
2000 mg/kg bw:
- non-survivng animals: discoloration in spleen was found in 1/2 female
- surviving animals sacrificed at termination: no abnormal findings

Any other information on results incl. tables

Table 1. Summary of results

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
Control	0/0/5	---	---	---
500	0/4/5	15 min – 3 h	---	0
1000	0/4/5	15 min – 3h	---	0
2000	3/5/5	15 min – day 4 (surviving)	1 – 3 h	60
Females
Control	0/0/5	---	---	---
500	0/3/5	15 min – 1 h	---	0
1000	0/5/5	15 min – 1 h	---	0
2000	2/5/5	15 min – day 3 (surviving)	1 h – day 2	40
LD50 = 2000 mg/kg bw

* first number = number of dead animals

second number = number of animals with clinical signs

third number = number of animals used

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

CLP: Acute toxicity, Cat. 4, H302