2-anilinoethanol

Endpoint summary

Description of key information

The oral LD50 was determined to be > 55 mg/kg.
The inhalation LC50 could not be determined.
The dermal LD50 was determined to be 68.7 mg/kg.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP non-guideline study, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

According to BASF-internal method: Two cats exposed orally to preparations of the test substance. Documentation of the clinical signs was performed over the 30 hour study period. Necropsy was performed at the end of the study.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

cat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 4.15 kg and 2.84 kg

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Test concentration used was 1% (v/v); aqueous solution

Doses:

0.05 mL/kg

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 30 hours
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, other: clinical chemistry for methemoglobin

Sex:

male

Dose descriptor:

LD50

Effect level:

> 0.05 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Corresponding to 55 mg/kg bw

Mortality:

No mortality observed.

Clinical signs:

other: Heavy breathing, cyanosis, salivation, apathy, and balance disorders were observed. After 1 day, no symptoms were observed.

Gross pathology:

Blackish brown blood, brown coloured lungs, pulmonary oedema, liver with yellow parts, and a bladder filled with brownish yellow urine were observed.

Other findings:

Methemoglobin up to 69%

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

Four acute oral toxicity studies are available presented in three reports, with three species. One study is considered to be klimisch 4, because only very limited study information is available. All other studies are regarded as klimisch 2.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP non-guideline study, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

BASF internal method

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

Rate of air: 200 L/h

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

0.17 mg/L

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Remarks on result:

other: LD50 > saturated vapour pressure

Mortality:

No mortality observed

Clinical signs:

other: Mucosal irritations: bloody eyes and nasal discharge. The following day animals were without symptoms.

Gross pathology:

In 1 animal chronic bronchitis was observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Two acute inhalation toxicity studies are avaible, performed with the same species. Both studies are regarded as klimisch 2.

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: Data published in peer reviewed literature, restrictions in design and/or reporting but contributing to a weight of evidence assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Penetration of rabbit skin is estimated by a technique closely skin to the one-day cuff method fo Draize and associates, using group of four male albino New Zealand rabbits. Based upon mortalities during a 14-day observation period the most probable LD50 and is fiducial range are estimated by the method of Thompson.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped trunk
- Type of wrap if used: impervious plastic film

REMOVAL OF TEST SUBSTANCE
- No washing
- Time after start of exposure: 24 hours

The animals are immobilized during the exposure period.

Duration of exposure:

24 hours

No. of animals per sex per dose:

4 males per group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

Most probable LD50 value and its fiducial range (± 1.96 SD) are estimated by the method of Thompson using the Tables of Weil

Sex:

male

Dose descriptor:

LD50

Effect level:

0.063 mL/kg bw

Based on:

test mat.

95% CL:

0.043 - 0.094

Interpretation of results:

highly toxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

68.7 mg/kg bw

Quality of whole database:

Two acute dermal toxicity studies are available, performed in two species. Both studies are regarded as klimisch 2.

Additional information

Acute toxicity: oral

Four acute oral toxicity studies are performed with three different species. In all of these studies limited information on the method of study has been reported. In the key study (BASF 1967, cat) two cats were exposed by oral gavage to 0.05 mL/kg of the test substance. After an observation period of 30 hours the animals were necropsied. No mortality was observed. Methemoglobin levels up to 69%, heavy breathing, cyanosis, salivation, apathy, and balance disorders were observed. Upon necropsy blackish brown blood, brown coloured lungs, pulmonary oedema, liver with yellow parts, and a bladder filled with brownish yellow urine were observed. In the second study (BASF 1967, rat) five US rats per sex per dose were exposed to the test substance dissolved in an aqueous emulsions of Traganth. Animals received 0.2, 1.6, 2, 2.5, 3.2 mL/kg bw (equivalent to 218, 1744, 2180, 2725, 3488 mg/kg bw) of the test substance via oral gavage. After an observation period of 7 days animal were necropsied. The LD50 was determined to be 2.5 mL/kg, which is equivalent to 2725 mg/kg bw. After one day crouching, irregular breathing, roughed fur, and sticky eyes were observed. No clinical signs were observed after three days. Crusting of the nose, a faeces smeared anus, and yellow-red dotted livers were observed upon pathology in animals that died. Surviving animals presented enlarged spleens and fatty livers. In the third study (Smyth 1962) groups of five non-fasted Carworth-Wistar male rats were exposed to the test substance via oral gavage. The dosages were arranged in a logarithmic series differing by a factor of two. Based upon mortalities during a 14-day observation period the most probable LD50 (± 1.96 SD) was estimated, by the method of Thompson, to be 2.23 mL/kg bw (2.01-2.47). In the fourth study (Bass 1942) two dogs were exposed to the test substance orally. One animal received 63 mg/kg bw and the other 140 mg/kg bw. No mortality was observed. As the rat is comparable insensitive for methemoglobin formation, the study conducted with cats was considered best appropriate for classification and labeling purposes.

Acute toxicity: inhalation

Two acute inhalation toxicity studies are performed both with rats. In both of these studies limited information on the method of study has been reported. In the first study (BASF 1967) six rats per sex were exposed to 0.17 mg/L of vaporized test substance for 8 hours. After an observation period of 7 days animals were necropsied. No mortality was observed. Mucosal irritations were observed which disappeared within one day, and upon necropsy chronic bronchitis was observed in one animal. In the second study (Smyth 1962) groups of six male or females albino rats were exposed to the test substance in an inhalation hazard test. Inhalations were continued for time periods in a logarithmic series with a ratio of two extending from one-fourth to eight hours, until the inhalation period killing about half the number of rats within 14 days was defined. No mortality was observed.

Acute toxicity: dermal

Two acute dermal toxicity studies are performed. In both of these studies limited information on the method of study has been reported. In the first study (BASF 1967) two cats were dermally exposed to 0.5 mL/kg of the test substance. Documentation of the clinical signs was performed over the 30 hour study period. Necropsy was performed at the end of the study. Heavily breathing, cyanosis, salivation, lying in the lateral position, no food consumption, and balance disorders were observed in both animals. A methemoglobin up to 83%, blackish brown blood, brown coloured lungs, pulmonary oedema, liver with yellow parts, and a bladder filled with brownish yellow urine were observed in one animal. The other animal had similar symptoms, but without the pulmonary oedema and with an empty stomach were observed upon necropsy. The LD50 was determined to be <0.5 mL/kg bw. In the second study (Smyth 1962) penetration of rabbit skin was estimated by a technique closely skin to the one-day cuff method fo Draize and associates, using group of four male albino New Zealand rabbits. Based upon mortalities during a 14-day observation period the most probable LD50 (and its fiducial range) was estimated, by the method of Thompson, to be 0.063 mL/kg bw (0.043-0.094) which is equivalent to 68.7 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Four acute oral toxicity studies are available, performed in three species. The study on cats was considered as the most reliable study for C&L puposes, since the cat is the most sensitive species for methemoglobin formation.

Justification for selection of acute toxicity – inhalation endpoint
Two acute inhalation toxicity studies are available, performed in the same species. The study which included dose level information has been selected as key study.

Justification for selection of acute toxicity – dermal endpoint
Two acute dermal toxicity studies are available, performed in two species. The study with a 14-day observation period following administration was considered most appropriate for C&L purposes.

Justification for classification or non-classification

Based on the massive methemoglobin formation after single application of 55 mg/kg bw to cats 2-anilinoethanol has to be classified for acute toxicity cat.3: H301: Toxic if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

 

Based on the available information on 2 -anilinoethanol, classification for acute inhalation toxicity is not possible in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

 

Based on a dermal LD50 of 68.7 mg/kg bw 2-anilinoethanol has to be classified for acute toxicity Cat 2: H310: Fatal in contact with skin in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.