2,4-dichlorobenzyl alcohol

Endpoint summary

Description of key information

The acute oral LD50 in mice was 2455 mg/kg bw, in ducks > 2510 mg/kg bw and in rats > 3000 and > 4800 mg/kg bw.  

The acute inhalation LD50 was > 2.04 mg/L in rats.

The acute dermal LD50 was > 2000 mg/kg bw in rats.

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:

June to August 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Experimental study with basic information given

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test substance was administered to rats orally once and obseration was done for 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Boots wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 70-95 g
- Fasting period before study: 4 h
- Housing: 10 per cage
- Diet: ad libitum, Oxoid Breeding Diet
- Water: ad libitum, tap water

Route of administration:

oral: unspecified

Vehicle:

other: 10 % (w/v) aqueous acacia solution.

Details on oral exposure:

VEHICLE
- Amount of vehicle: 0.2 mL /100 g

Doses:

approx. 3000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation was done for 2 h after dosing and afterwards daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Mortality:

3 male animals died within 24 h after treatment.

Clinical signs:

Signs were detected soon after treatment.
Following signs were detected: Coma (1 male), prostration (1 male), inactivity (8 male, 10 female), ataxi (8 male, 10 female), slow respiration (2 male)

Body weight:

No data.

Gross pathology:

No abnormalities were detected during autopsy in 10 female and 7 male animals. The 3 male animals that died after treatmen were not examined due to autolysis.

Interpretation of results:

not classified

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 455 mg/kg bw

Quality of whole database:

The data was determined to be suitable for classification.

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:

1997-06-18 to 1997-07-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Experimental study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Version / remarks:

The study design was in compliance with EEC, OECD, EPA and JMAFF test guidelines for acute inhalation studies.
Deviation: The test atmosphere could not be produced from the test substance using the Wright dust generator because of the crystalline nature of the test substance. A solution in acetone (50:50 w/w) was prepared and a liquid draplet aerosol generated from the solution using a stainless steel concentric jet atomiser. This deviation from the study protocol was necessary to conduct the study.

Deviations:

yes

Principles of method if other than guideline:

The study design was in compliance with EEC, OECD, EPA and JMAFF test guidelines for acute inhalation studies.
Deviation: The test atmosphere could not be produced from the test substance using the Wright dust generator because of the crystalline nature of the test substance. A solution in acetone (50:50 w/w) was prepared and a liquid draplet aerosol generated from the solution using a stainless steel concentric jet atomiser. This deviation from the study protocol was necessary to conduct the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd. Manston Road, Margate, Kent, England
- Age at study initiation: 8-9 weeks
- Weight at study initiation: male: 185-204 g, female: 175-200 g
- Fasting period before study: no
- Housing: 5 animals per cage (same sex), metal cages with wire mesh floors
- Diet: ad libitum, Special Diet Services RM 1
- Water: ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-20
- Humidity (%): 46-61
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: acetone

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: The rats were held for exposure in moulded polycarbonate tubes which were attached at evenly spaced ports in the cylindrical section of the chamber. The tubes were tapered at one end to allow the snout only to project into the chamber. Ibe other end was closed by insertion of an expanded plastic bung. A push rod passed through the centre of the bung and was adjusted to maintain the position of a rat during exposure.
- Source and rate of air: clean dried air, 15 L/min
- Method of conditioning air: aerosol generator
- System of generating particulates/aerosols: concentric jet atomiser
- Method of particle size determination: A sample (1.5 L) of the chamber atmosphere was drawn through a Marple (Model 296) Personal Cascade Impactor (Graseby Andersen Ltd., Georgia, USA) with stainless steel collection substrates and a Whatman GF/A filter. The sample volume was measured using a wet-type gas meter placed in-line with the pump. The sampling rate (2 1/minute) was set before use, using a tapered tube rotameter. Each collection substrate was weighed before and after sampling.
- Temperature, humidity, pressure in air chamber: 19-20 °C, 42-43 % relative humidity

TEST ATMOSPHERE
- Brief description of analytical method used: Five air samples were taken from the chamber during each exposure and the concentration in the chamber air was determined by chemical analysis.
- Samples taken from breathing zone: no

VEHICLE
- Composition of vehicle: Acetone
- Concentration of test material in vehicle: 50:50 w/w

TEST ATMOSPHERE
- Particle size distribution: total amount collected at 1.5 h was 1936.1 µg and at 3.5 h 2241.5 µg.
- MMAD: 2.9 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

in air: 2.04 mg/L
nominal: 22.2 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. The clinical signs were recorded at the end of the chamber equilibration period, followed by recordings at 0.25, 0.5 and 1.0 hour and at hourly intervals, thereafter, during the exposure. Further recordings were made at 0, 1 and 2 hours post-exposure. During the observation period, the clinical signs were recorded once in the morning and then, following a later check for clinical signs, as deemed necessary. Body weight was determined daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, food and water consumption

Statistics:

No data provided.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.04 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality observed.

Clinical signs:

other: During the exposure all animals showed exaggerated respiratory movements. Following the exposure 3 male and 2 females were lethargic. The fur of all animals was wet around the snout and jaws. During the observation period, exaggerated respiratory movement

Body weight:

There was a slight reduction in the rate of bodyweight gain of male rats on the day following exposure, females were unaffected. Otherwise, the rate of bodyweight gain for test rats was similar to that of the vehicle controls.

Gross pathology:

There were no macroscopic abnormalities in test or control rats.

Other findings:

- Organ weights: The lung weight for test rats was similar to that of the controls.
- Other observations: Food consumption was moderately reduced in male test rats for up to 4 days and slightly reduced in female test rats for 1 - 2 days following exposure. Food consumption for test rats was otherwise similar to that of the vehicle control rats during the observation period. Water consumption for test rats was similar to that of the controls.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2 040 mg/m³

Quality of whole database:

The data was determined to be suitable for classification.

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

Study period:

1997-07-01 to 1997-07-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Experimental study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Version / remarks:

1985

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animais 81-2 Acute dermal toxicity study (Revised Ed. November 1984). Subdivision F provides information on data requirements of 40 CFR Part 158 and supports FIFRA.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England
- Age at study initiation: 11 weeks
- Weight at study initiation: 210 to 254 g
- Fasting period before study: no
- Housing: 5 animals per cage (same sex), metal cages with wire mesh floors
- Diet: ad libitum, Special Diet Services RM 1 (E)SQC expanded pellet
- Water: ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 40-64
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: 1 % (w/v) aqueous methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region (approximately 50 mm x 50 mm)
- % coverage: approximately 10 % of total body surface
- Type of wrap: porous gauze held in place with a non - irritating dressing, covered by a waterproof dressing, encircled firmly around the trunk of the animal

REMOVAL OF TEST SUBSTANCE
- Washing: warm water (30 to 40 °C)
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 4 mL/kg bw (test material in vehicle)
- Concentration: 50 % w/v
- Constant volume or concentration used: yes

VEHICLE
- Amount applied: 4 mL/kg bw (test material in vehicle)
- Concentration: 1 % w/v

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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: Animals were observed after dosing and at frequent intervals for the remainder of Day 1. Afterwards animals were observed once in the morning and once in the aflernoon (Day 15 - morning only). Body weight was recorded on day 1 (before treatement), day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal responses

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No clinical signs were observed.

Body weight:

Body weight gain was in the normal range.

Gross pathology:

No abnormalities were observed.

Other findings:

Dermal response:
very slight erythema (grade 1) was detected in 4 animals after removal (day 2). In 3 animals no signs were detected on day 3. In one animal it was detected till day 5, accompanied by desquamation (day 2 to 7). Afterwards no further dermal responses were observed.

Interpretation of results:

not classified

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The data was determined to be suitable for classification.

Additional information

Oral

In an oral study (BASF SE.1975) ten male and ten female rats were administered the test substance at a dose of approx. 3000 mg/kg bw. A control group of 10 males and 10 females was administered the vehicle, a 10 % acacia solution alone. All animals were observed for 14 days. Three dosed males died within 3 to 19 hours after dosing. Several rats showed different clinical signs. Those were coma (1 male), prostration (1 male), inactivity (8 male, 10 female), ataxi (8 male, 10 female) and slow respiration (2 male). The oral LD50 was determined to be > 3000 mg/kg bw for rats.

 

An oral study in mice was conducted to evaluate the acute toxicity of the test substance (BASF SE. 1982). Groups of 10 male Cre/TO mice were administered the product at doses of 1000, 1500, 2250, and 3375 mg/kg bw and forty control mice were administered the vehicle. All animals were observed for 14 days. 1/10, 4/10, and 8/10 mice administered 1500, 2250, and 3375 mg/kg of the test substance in vehicle, respectively, died within 24 hours after administration. Other animals treated with 1500, 2250, and 3375 mg/kg bw showed several clinical signs of toxicity. The LD50 of the test substance in mice was determined to be 2455 mg/kg bw.

 

The oral toxicity study (BASF SE.1960) used groups of 10 rats for an administration of the test substance at doses of 1200, 2400, 3600, and 4880 mg/kg bw as a suspension in 10 % aqueous acacia solution. Animals were observed for 14 days. One rat given 3600 mg/kg bw died within 24 hours after dosing. Two rats given 4800 mg/kg bw died; the deaths occurred within 24 hours after dosing and at day 4 after dosing. The LD50 was determined to be > 4800 mg/kg bw in rats.

 

An acute oral toxicity study was conducted in Mallard ducks (BASF SE.1981). The test substance was administered orally at doses of 398, 631, 1000, 1590 and 2510 mg/kg bw. The animals were observed for 14 days. Several clinical signs were detected after treatment, including lethargy, reduced reaction to external stimuli, lower limb weakness and loss of coordination. All effects were detected in the first 3 days and afterwards animals were symptom free. No animal died after treatment with the test substance. Therefore the LD50 for acute oral toxicity in ducks was established to be > 2510 mg/kg bw.

In conclusion the test substance is not classified for acute oral toxicity.

 

Inhalation

A group of 5 male and 5 female Sprague-Dawley rats was exposed for 4 h to a test atmosphere containing a liquid droplet aerosol generated from a solution of the test substance in acetone (50/50 w/w). The concentration of the test substance was 2.04 mg/L (measured). A control group of 5 males and 5 females was exposed to the vehicle. All rats were observed for 14 days. No animal died. Clinical signs included wet fur and brown staining around the snout or jaws (observed in both test and control rats); and exaggerated respiratory movements, lethargy, as well as slight reduction of food consumption and body weights (observed in test rats). Control and test rats were normal in appearance and behavior at day 2 and 4 of observation, respectively. The LD50 for acute inhalation was derived to be > 2.04 mg/L of the test substance in air. 

 

Dermal

A group of 5 male and 5 female Sprague-Dawley rats was treated dermally with 2000 mg/kg bw of the test substance under occlusive conditions. After 24 hours, the application patches were removed and residual material was washed off. The rats were observed for 14 days. No deaths and no systemic reactions were observed. Very slight erythema (grade 1) was detected in 4 animals after removal (day 2). In 3 animals no signs were detected on day 3. In one animal it was detected till day 5, accompanied by desquamation (day 2 to 7). Afterwards no further dermal responses were observed. The acute dermal LD50 was determined to be > 2000 mg/kg bw in rats.

Justification for selection of acute toxicity – oral endpoint

Study conducted in rats with most details provided was selected and the result was supported by other studies.

Justification for selection of acute toxicity – inhalation endpoint

Only study available.

Justification for selection of acute toxicity – dermal endpoint

Only study available.

Justification for classification or non-classification

Acute oral toxicity

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/1221. As a result the substance is considered to be not classified for acute oral toxicity.

 

Acute inhalation toxicity

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/1221. As a result the substance is considered to be classified for acute inhalation toxicity (mist) in Category 4. H332: Harmful if inhaled.

 

Acute dermal toxicity

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221. As a result the substance is considered to be not classified for acute dermal toxicity.