Registration Dossier

Administrative data

Description of key information

acute toxicity, oral (OECD 401, RL1), male rats: LD50 > 1000 > 2000 mg/kg bw

acute toxicity, inhalation (OECD 403, RL2), rats: LC50 > 4.77 mg/L air

acute toxicity, dermal (no guideline followed, RL2): LD50 > 1000 > 1580 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Reference:
Composition 1
Qualifier:
according to
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 information:
Composition 1
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
Species:
rat
Strain:
Crj: CD(SD)
Remarks:
Crj:CD(SD)IGS
Sex:
male/female
Details on test animals 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

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
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.
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
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
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

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

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute toxicity, Cat. 4, H302
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable (RL1) key study. The information is therefore sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 Jun - 18 Jul 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited details on inhalation exposure given, no data on MMAD given
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
as adopted 12 May 1981
Deviations:
yes
Remarks:
limited data on inhalation exposure given, no data MMAD given
GLP compliance:
yes
Test type:
traditional method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Hoechst Celanese Corporation, batch 55312
- Expiration date of the lot/batch: 30 Dec 1991
- Purity test date: >99%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored at room temperature, in the original container, protected from light

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was used as supplied.

FORM AS APPLIED IN THE TEST (if different from that of starting material): For the low and mid dose group the test material was administered following vaporization. For the high dose group the test material was nebulized followed by filtration.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd, CH-4414 Fuellinsdorf, Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: males: 8 weeks; females 10 weeks
- Weight at study initiation: males: 180 - 192 g; females: 186 - 200 g
- Housing: in groups of five in Makrolon cages type 4 with softwood bedding
- Diet: pelleted standard Kliba 343 maintance diet, ad libitum
- Water: community tap water from Geneva, ad libitum
- Acclimation period: 4 to 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 15
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod: 12/12

IN-LIFE DATES: From: 24 Jun 1991 To:18 Jul 1991
Route of administration:
other: Inhalation: For the low and mid dose group the test material was administered following vaporization. For the high dose group the test material was nebulized followed by filtration.
Type of inhalation exposure:
nose only
Vehicle:
air
Remark on MMAD/GSD:
no data provided
Details on inhalation exposure:
no data provided
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.089, 0.546 and 4.77 mg/L air (analytical concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and mortality were observed daily. Body weights were recorded prior to exposure and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights
Statistics:
A statistical analysis was not necessary/possible as no mortalities were noted.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 4.77 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortalities occurred during the study.
Clinical signs:
Restlessness was noted in all animals of the high dose group (4.77 mg/L) during exposure. This sign as well as hunched posture, ruffled fur and tachypnea (males only) were observed on test day 1 after exposure. Ruffled fur lasted until test day 2 in all high dose animals.
Body weight:
No treatment-related effects on body weights were noted.
Gross pathology:
Isolated dark red or reddish foci were noted on one or several lung lobes of 2 males and 2 females, 4 males and 2 females of the low and mid dose group, respectively. No necropsy findings were noted in animals of the high dose group.

Table 1. Table for acute toxicity following inhalation

Target concentration
[mg/L air]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

0.089

0/0/5

---

---

0

0.546

0/0/5

---

---

0

4.77

0/5/5

Day 1-2

---

0

Females

0.089

0/0/5

---

---

0

0.546

0/0/5

---

---

0

4.77

0/5/5

Day 1-2

---

0

LC50 > 4.77 mg/L air

* first number = number of dead animals   

 second number = number of animals with clinical signs

 third number = number of animals used 

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
2-chlorophenol is classified as Acute Tox. 4, H332 according to Annex VI of Regulation (EC) No 1272/2008. Although the available data on acute toxicity following inhalation do not meet the classification criteria according to Regulation (EC) No 1272/2008, the registrant follows the harmonised classification.
Conclusions:
CLP: Acute toxicity, Cat. 4, H332
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
4 770 mg/m³
Quality of whole database:
The available information comprises an adequate and reliable (RL2) key study. The information is therefore sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Remarks:
(no details on study design and results provided)
Reference:
Composition 1
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: 4 New Zealand white rabbits were exposed to the test item for 24 h. Applied doses were 631, 1000 and 1580 mg/kg bw, group sizes were n=1, n=1 and n=2, respectively. The observation period was 14 days.
- Parameters analysed / observed: mortality, clinical signs, gross autopsy
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
-Lot/batch No.of test material: KL 1003
Species:
rat
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
631, 1000, 1580 mg/kg bw
No. of animals per sex per dose:
631 mg/kg bw: 1 female
1000 mg/kg bw: 1 male
1580 mg/kg bw: 1 male and 1 female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross autopsy
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 1 580 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was observed after topical application of 1580 mg/kg bw in 2/2 test animals within 2 days. No mortalities were noted at the mid and low dose.
Clinical signs:
Reduced appetite and activity (three to five days in survivors), increasing weakness, collapse and death were observed.
Gross pathology:
In decedents, lung and liver hyperemia, enlarged gall bladder, darkened kidney and spleen, and gastrointestinal inflammation were observed.
In survivors, viscera appeared normal after the end of the observation period of 14 days.

Dose
[mg/kg bw]
Toxicological results* Mortality (%)
Males    
631 0/0 ---
1000 0/1 0
1580 1/1 100
Females    
631 0/1 0
1000 0/0 ---
1580 1/1 100
LD50 >1000 < 1580 mg/kg
* first number = number of dead animals
 second number = number of animals used
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute toxicity, Cat. 4, H312
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable (RL2) key study. The information is therefore sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity

Data on acute toxicity of 2-chlorophenol are available following oral and dermal exposure and inhalation.

Acute oral toxicity

Acute toxicity of 2-chlorophenol was tested in Crj/CD (SD) rats according to OECD TG 401 (reference 7.2.1-1). Based on the results of a preliminary test, the test substance was administered at concentrations of 500, 1000 and 2000 mg/kg bw in olive oil via gavage to groups of 5 males and females. A concurrent control group was included in the study. In the high dose group, 3/5 males and 2/5 females died. No mortality was observed in the lower dose groups. Clinical signs indicative for systemic toxicity were observed in all dose groups, including decreased locomotor activity, abnormal gait, clonic convulsion and lateral or prone position. Furthermore, slightly decreased body weight gains were observed in surviving animals of the high dose group at Day 4. In the lower dose groups, body weight gain appeared normal. Necropsy examination revealed discoloration in the spleen in 1/2 deceased females. In the remaining animals (surviving or deceased), no abnormal findings were reported. Based on the observed mortalities, a LD50 > 1000 < 2000 mg/kg bw was derived for males. In females, a LD50 > 2000 mg/kg bw was apparent. Thus, as the male animals appeared to be the most sensitive species, an overall LD50 > 1000 < 2000 mg/kg bw is considered for 2-chlorophenol.

In conclusion, 2-chlorophenol is considered to exhibit hazardous properties after single exposure. A LD50 > 1000 < 2000 mg/kg bw is derived.

Based on the results of the conducted study, 2-chlorophenol meets the classification criteria for Acute toxicity, Cat. 4, H302 according to Regulation (EC) No 1272/2008.

Inhalation

An acute inhalation toxicity study was performed according to OECD TG 403 and in compliance with GLP with 2-chlorophenol (reference 7.2.2-1). In this study, groups of 5 male and 5 female Wistar rats were exposed to single doses of 0.089, 0.546 and 4.77 mg/L air (analytical concentration) test substance for 4 h via nose only inhalation. The low and mid concentrations were administered as vapour and for the high dose the test substance was nebulized followed by filtration. Animals were observed for 14 days after test material exposure. No mortality occurred during the entire study period and clinical signs of toxicity were limited to high dose animals which revealed restless behavior during exposure. On day one after exposure, hunched posture, ruffled fur and tachypnea (males only) were observed in this dose group. Ruffled fur lasted until test day 2 in all high dose animals. No effects on body weight were noted. Necropsy examination revealed red foci on the lungs of the low and mid dose animals, but not on lungs of high dose animals. The acute inhalation LC50 value is considered to be > 4.77 mg/L air.

In conclusion, based on the available data, 2-chlorophenol did not exhibit hazardous properties after single exposure following inhalation. A LC50 > 4.77 mg/L air is derived. However, according to the harmonised classification, 2-chlorophenol is considered to meet the classification criteria for Acute toxicity, Cat. 4, H332 according to Regulation (EC) No 1272/2008.

Dermal

An acute dermal toxicity study was performed with 2-chlorophenol (reference 7.2.3-1). In this study, groups of 1 female, 1 male and 2 (1 female/1 male) New Zealand White rabbits were exposed to single doses of 631, 1000 and 1580 mg/kg bw test substance for 24 h, respectively. The observation period was 14 days. Mortality occurred in both high dose animals within two days following exposure. No mortalities were noted at the mid and low dose. Clinical signs of toxicity were noted at all doses and comprised reduced appetite and activity (three to five days in survivors), increasing weakness and collapse (no details on affected groups given). Necropsy examination of decedents revealed lung and liver hyperemia, enlarged gall bladder, darkened kidney and spleen as well as gastrointestinal inflammation. In survivors, viscera appeared normal after the end of the observation period. Based on the observed mortalities in the high dose group, a LD50 > 1000 < 1580 mg/kg bw is derived.

In conclusion, 2-chlorophenol is considered to exhibit hazardous properties after single exposure. A LD50 > 1000 < 1580 mg/kg bw is derived.

Based on the results of the conducted study, 2-chlorophenol meets the classification criteria for Acute toxicity, Cat. 4, H312 according to Regulation (EC) No 1272/2008.

Justification for classification or non-classification

2-chlorophenol is classified as Acute Tox. 4, H302, H312 and H332 according to Annex VI of Regulation (EC) No 1272/2008. Although the available data on acute toxicity following inhalation do not meet the classification criteria according to Regulation (EC) No 1272/2008, the registrant follows the harmonised classification.