Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with ethanolamine

Endpoint summary

Description of key information

MEA-LAS dissociates into LAS and MEA in aqueous media and therefore the acute oral toxicity of both compounds has been studied. Results of the acute toxicity studies indicate that the lowest acute LD50 (oral) is 1080 mg/kg bw, whereas the lowest acute dermal LD50 is 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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: Meets generally accepted scientific standards, acceptable for assessment.

Principles of method if other than guideline:

Groups of 5 rats/sex were treated by gavage with 200, 400, 800, 1000, 1250, 1600 or 3200 mL/kg bw of the test material to determine the acute oral LD50

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 % (200 mL/kg bw), 4 % (400 and 800 mL/kg bw), 8 % (1000 and 1250 mL/kg bw) and 20 % (1600 and 3200 mL/kg bw)

Doses:

200, 400, 800, 1000, 1250, 1600, 3200 mL/kg bw (equivalent to 202, 404, 808, 1010, 1262.5, 1616 and 3232 mg/kg bw, respectively)

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 515 mg/kg bw

Remarks on result:

other: ca. 1500 mL/kg bw (calculated with a specific density of 1.01 g/mL)

Mortality:

All males and females treated with 3200 mL/kg bw died within 24 hours. Two males and four females treated with 1600 mL/kg bw died within the first 48 hours. None of the animals treated with 200, 400, 800, 1000 or 1250 mL/kg bw died.

Clinical signs:

other: Animals treated with 3200 or 1600 mL/kg bw exhibited calm behavior and abdominal position after application. Animals treated with 1600 mL/kg bw also exhibited calm behavior, slight staggering and piloerection in the following observation days, until day 7

Gross pathology:

Animals that survived to study termination showed no internal abnormalities at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral toxicity (LD50) of 2-aminoethanol was determined to be ca. 1515 mg/kg bw (ca. 1500 mL/kg bw; calulated with a specific density of 1.01 g/mL). The test material is therefore classified as Category 4 based on GHS criteria.

Executive summary:

The objective of this study was to determine the acute oral toxicity (LD50) of 2-aminoethanol when administered once orally to male and female rats.

Male and female Sprague-Dawley rats were used in this study. The test material was administered by oral gavage as 2% (200 mL/kg bw), 4% (400 and 800 mL/kg bw), 8% (1000 and 1250 mL/kg bw) and 20% (1600 and 3200 mL/kg bw) aqueous solutions to the animals (10 rats/dose). These doses corresponds to 200, 404, 808, 1010, 1262.5, 1616 and 3232 mg/kg bw (calculated on the basis of density of 1.01 g/ mL at 20 °C).

Post treatment, animals were examined for mortality, clinical signs and body weight changes upto day 7. After 7 days of observation, all surviving animals were euthanized, subjected to necropsy and examined for gross pathological changes. Mortalities were observed in all animals treated with 3200 mL/kg bw dose within 24 hours while two males and four females died within first 48 hours in the group treated with 1600 mL/kg bw. No mortality was observed in animals treated with 200, 400, 1000 and 1250 mL/ kg bw doses.

At 3200 and 1600 mL/kg bw doses, animals exhibited calm behaviour and abdominal position after application. Animals treated with 1600 mL/kg bw dose also exhibited slight staggering and piloerection during observation till day 7. Squatting posture and calm behaviour was observed upto 24 hours after treatment in 1250 and 1000 mL/kg bw dose groups and no clinical signs were noted in these groups after day 4. No clinical signs were observed in 800 and 400 mL/kg bw dose groups while slight staggering was noted in animals treated with 200 mL/kg bw on first two days of this study and no clinical signs were observed later on. No abnormal changes in body weight were reported. No abnormal gross pathological alterations were observed at the end of 7 days observation period in

surviving animals at necropsy.

Based on the above observation, the acute oral toxicity (LD50) of 2-aminoethanol was determined to be ca. 1515 mg/kg bw (ca. 1500 ml/kg bw; calulated with a specific density of 1.01 g/mL).

The test material is therefore classified as Category 4 based on GHS criteria.4

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(substance purity not given)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-300 g
- Fasting period before study: over night

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

0.25, 0.50, 1.0, 2.0, 4.0 mL/kg bw (based on a density of 1.018 g/mL: 254, 509, 1018, 2036, 4072 mg/kg bw)

No. of animals per sex per dose:

5 males and 5 females (0.25-2.0 mL/kg bw dosing groups)
2 males (4.0 mL/kg bw dosing group)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: on day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

LD50 values and the estimated LD50 slopes were calculated by the moving average method (Thompson 1947; Weil 1983).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 089 mg/kg bw

Based on:

other: based on a density of 1.018 g/mL

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1.19 mL/kg bw

95% CL:

> 0.79 - < 1.8

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1.07 mL/kg bw

95% CL:

> 0.72 - < 1.59

Mortality:

Dose (mL/kg bw) Numbers of Animals Dead Time of Death
(M,F)
0.25 0,0 N/A
0.50 1,0 12 days
1.0 1,2 1 or 2 days
2.0 5,5 4 hrs to 1 day
4.0 2 (M) 3 hrs
All deaths occurred relatively rapidly after dosing (within 2 days), except for one male rat that died after 12 days after a dose of 0.5 mL/kg bw. Both of the male rats receiving monoethanolamine at the maximum peroral dosage of 4.0 mL/kg bw died after 3 hours. One female in the 2.00 mL/kg bw group died after 4 hours.

Clinical signs:

other: MALES Dosage (mL/kg bw) Signs of Toxicity 4.00 sluggishness at 15 min; slight piloerection at 1 hr. death at 3 hr. 2.00 sluggishness at 1.5 hr; slight piloerection at 2 hr. 1.00

Gross pathology:

MALES
Dosage (mL/kg bw) Gross Pathology
4.00 lungs pale red; stomachs, intestines dark red.
2.00 lungs of 1 mottled light and dark red; stomachs, intestines distended, filled with dark red liquid.
1.00 in deceased, stomach, intestines red; stomach filled with clear red liquid; in survivors, kidneys mottled dark red.
0.50 in deceased, stomach severely distended, filled with brown liquid; emaciation; in survivors, nothing remarkable.
0.25 nothing remarkable

FEMALES
Dosage (mL/kg bw) Gross Pathology
2.00 lungs mottled or bright red; stomachs, intestines dark red, filled with red liquid.
1.00 in deceased, glandular portion of stomachs dark red; in survivors, livers of 2 adhered to glandular portion of stomachs ; stomachs distended with gas; kidneys dark red.
0.50 liver of 1 adhered to glandular portion of stomach; stomach of 1 distended with gas; kidneys of 1 dark red.
0.25 nothing remarkable

The LD50 values (with confidence limits if calculated) in males and females were 1.19 (0.79 - 1.80) mL/kg bw and 1.07 (0.72 - 1.59) mL/kg bw, respectively. The slopes of the curves were 3.84 and 4.96 for males and females, respectively.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral toxicity (LD50) of 2-aminoethanol was determined to be 1089 mg/kg bw (based on density of 1.018 g/mL) in rats, 1.19 (95% CL: 0.79 - 1.8) mL/kg bw for male rats and 1.07 (95% CL: 0.72 - 1.59) mL/kg bw for female rats. The test material is therefore classified as Category 4 based on GHS criteria.

Executive summary:

The purpose of this study was to determine the acute oral toxicity (LD50) of 2-aminoethanol when administered once orally to male and female rats.

Sprague-dawley rats weighing 200 - 300 g were used in this study. The animals were fasted over night prior to the dosing. The test material was administered by oral gavage at following doses (10 animals (5 male and 5 female)/dose for 0.25 to 2.0 mL/kg bw and 2 males for 4.0 mL/kg bw): 0.25, 0.50, 1.0, 2.0 and 4.0 mL/kg bw. These doses corresponds to 254, 509, 1018, 2036 and 4072 mg/kg bw (calculated on the basis of density of 1.018 mg/L).

Post treatment animals were examined for mortality, clinical signs and body weight changes upto day 14. After 14 days of observation, all surviving animals were euthanized, subjected to necropsy and examined for organ weight and gross pathological changes.

No mortality was observed at 0.25 mL/kg bw dose. Mortalities observed at 0.50, 1.0, 2.0 and 4.0 mL/kg bw doses were one male after 12 days, one male and two females within 1 - 2 days, five males and five females within 4 hours - 1 day and two male rats after 4 hours of adminstration of test substance, respectively.

No clinical signs were observed at 0.25 ml/kg bw dose. At 0.50 and 1.0 mL/kg bw doses, animals showed sluggishness, lacrimation, red crust on perinasal and periocular fur, slight brown stain on periurogenital fur, emaciation, kyphosis, unkempt appearance and piloerection. Recovery was observed in the affected males after 2 days at 1.0 mL/kg bw dose while in females recovery was observed after 2 to 4 days at 0.50 mL/kg bw and only single survivor recovered after 2 days at 1.0 mL.kg bw dose. Sluggishness and piloerection were observed in animals before death at 2.0 and 4.0 mL/kg bw doses. Slight kyphosis, lacrimation, unsteady gait, red crust on perinasal and periocular fur along with the slight wetness of periurogenital fur were also observed in female rats at 2.0 and 1.0 mL/kg bw doses.

No abnormal changes in body weight were reported.

No remarkble gross pathological changes were observed at 0.25 mL/kg bw dose in all animals. In males at 0.50 mL/kg bw, no remarkable change was observed in survivours while stoamch wasemaciation,severely distended and filled with brown liquid in deceased while in female rats at this dose, liver of one female was adhered to the glandular portion of stomach, stomach of one female was distended with gas and kidneys of one female rat were of dark red colour. In male rats treated with 1.0 mL/kg bw dose, kidneys were mottled dark red in survivors and both stomach and intestines were red and filled with clear red liquid in deceased while in female rats, liver of two animals were adhered to the glandular portion of stomachs, kidneys were of dark red shade and stomach was distended with gas. In deceased female rats at this dose, glandular portion of stoamch was of dark red shade. At higher doses (4.0 mL/kg bw in male rats and 2.0 mL/kg bw in both male and female rats), lungs were mottled, had pale red to bright red colour and both stomach as well as intestines were of dark red colour. At 2.0 mL/kg bw doses in both sexes, stomach and intestines were also filled with dark red liquid.

Based on the above observations, the acute oral toxicity (LD50) of 2-aminoethanol was determined to be 1089 mg/kg bw (based on density of 1.018 g/mL) in rats, 1.19 (95% CL: 0.79 - 1.8) mL/kg bw for male rats and 1.07 (95% CL: 0.72 - 1.59) mL/kg bw for female rats.

The test material is therefore classified as Category 4 based on GHS criteria.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1970

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute oral toxicity or LD50 value was determined by oral administration of test substance to four dose groups of rats. Subsequently observations of effects (such as clinical signs, cage side observation) and deaths were made for 14 days.

GLP compliance:

no

Remarks:

(pre-GLP)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: The animals were obtained from Charles River Laboratories
- Weight at study initiation: 190-300 g
No other details on test animals and environmental conditions are provided in the study report.

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40% w/w
MAXIMUM DOSE VOLUME APPLIED: Not reported

Doses:

950, 1330, 1860 and 2600 mg/kg bw

No. of animals per sex per dose:

10 animals/dose. Sex of animal is not specified

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Animals were observed daily for clinical sign and symptoms.
- Necropsy: Yes, necropsy was performed.
- Other examinations performed: Animals were observed for motor activity increase, motor activity decrease, respiratory rate increase, respiratory rate decrease, loss of righting reflex, loss of corneal reflex, pupillary response, fine body tremors, coarse body tremors, blanching, gasping, salivation, abdominal griping, diarrhea and excess urination.

Statistics:

Not reported

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 570 mg/kg bw

Based on:

act. ingr.

95% CL:

> 1 390 - < 1 790

Mortality:

950 mg/kg bw: No mortality observed (0/10)
1330 mg/kg bw: 2 animals died out of 10 (2/10)
1860 mg/kg bw: 8 animals died out of 10 (8/10)
2600 mg/kg bw: All animals died (10/10)

Clinical signs:

other: Loss of righting reflex, loss of corneal reflex and pupillary response were observed in a few animals treated with the test substance.

Gross pathology:

No abnormalities related to test substance were observed in any of the test groups.

Other findings:

None

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of Monoethanolamine salt of dodecyl benzene sulfonic acid (MEA-LAS) when administered as 40% w/w aqueous solution in male and female rats was determined to be 1570 mg/kg bw, based on active level. MEA-LAS is therefore classified as OECD GHS Toxicity Category IV (Harmful if swallowed).

Executive summary:

The objective of the study was to determine the acute oral toxicity of Monoethanolamine salt of dodecyl benzene sulfonic acid (MEA-LAS) when administered as 40% w/w aqueous solution to male and female rats.

The test substance was diluted in water and administered orally to Charles River CD rats (weighing 190 -300 g) at the following dose levels: 950, 1330, 1860 and 2600 mg/kg bw

There were ten animals/dose group. Animals were observed for mortality and clinical signs daily for 14 d.

The clinical signs and mortality observed in tested groups were as follows: 0/10, 2/10, 8/10 and 10/10 animals died at 950, 1330, 1860 and 2600 mg/kg bw dose levels respectively. Loss of righting reflex, loss of corneal reflex and pupillary response were observed in a few animals treated with the test substance.

No abnormalities were noted in any of the test groups upon gross examination at necropsy.

Based on the above, the acute oral LD50 of Monoethanolamine salt of dodecyl benzene sulfonic acid (MEA-LAS) when administered as 40% w/w aqueous solution in male and female rats was considered as 1570 mg/kg bw, based on active level. MEA-LAS is therefore classified as OECD GHS Toxicity Category IV (Harmful if swallowed).

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan. 1, 1984-Feb. 14, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

The study examined oral toxicity of the test substance in rats. 5 male and 5 female rats were exposed orally to 0, 1075, 1220, 1360, or 1710 mg/kg of test substance and were then monitored for 14 days for mortality and clinical signs.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann
- Weight at study initiation: 123 g female, 146 g male
- Fasting period before study:
- Housing: 1-5 animals in Makrolon cages,
- Diet (e.g. ad libitum): R10 Alleidiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12.5-19.9% in water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

LAS doses of 1075, 1220, 1360, 1710 or a control
Note that all doses are corrected for 86% activity. The original doses were 1250, 1415, 1580 and 1990 mg/kg.

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Body weight and other signs were measured on days 7 and 14.
Animals were observed for 14 days after dosing.
Necropsies were performed at the end of the study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 080 mg/kg bw

Based on:

act. ingr.

Mortality:

Virtually all animals died in doses of 1220 mg/kg and above.

Clinical signs:

other: Symptoms beginning about 30 minutes past application included diarrhea, squatting attitude, breathing difficulties, nose bleeding, ataxia, and lethargy. These symptoms had disappeared in surviving animals by 120 hours.

Gross pathology:

In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In the surviving animals, hyperemia of the stomach was noted, along with abnormalities of the stomach, liver, spleen, kidneys, and the peritoneum.

Mortality

Dose (mg/kg)	Sex	Mortality
1075	Male	0
	Female	4
1220	Male	5
	Female	3
1360	Male	4
	Female	5
1710	Male	5
	Female	5

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 is 1080 mg/kg. The test material is therefore classified as Category 4 based on GHS criteria.

Executive summary:

This study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally to 0, 1075, 1220, 1360, or 1710 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 4 of 10 animals at the lowest dose level dying. All animals at the highest dose level died. The acute oral LD50, when adjusted for activity was 1080 mg/kg. The test material is therefore classified as Category 4 based on GHS criteria.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Feb. 1, 1984 To Feb. 21, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

The study examined oral toxicity of the test substance in rats. 5 male and 5 female rats were exposed orally to 2510, 2835, or 3160 mg/kg of test substance and were then monitored for 14 days for mortality and clinical signs.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Weight at study initiation: 111 g female, 121 g male
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Alleindiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 3.16 mL/kg

Doses:

2510, 2835, 3160 mg/kg test substance (Volume: 2.51 - 3.16 mL/kg)

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 (occurrence, nature and duration) and time of death were observed up to 6 hours after treatment and daily thereafter, weighing was performed before treatment and on days 1, 7 and 14 after treatment.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 760 mg/kg bw

Based on:

test mat.

95% CL:

> 2 579 - < 2 953

Mortality:

2510 mg/kg: 1 male and 2 females died within 24 hours
2835 mg/kg: 1 male and 4 females died within 24 hours
3160 mg/kg: 5 males and 4 females died within 24 hours

Clinical signs:

other: All animals showed signs of toxicity. Symptoms beginning about 60 minutes past application included piloerection, diarrhea, squatting attitude, diuresis, ataxia, nose bleeding and slight sedation. These symptoms had disappeared in surviving animals by 6

Gross pathology:

In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In some of the surviving animals, partial swelling of gastric mucosa and hyperemia of the small intestine was noted and in two animals adhesion of stomach, liver, spleen, and peritoneum was observed.

Mortality

Dose (mg/kg)	Sex	Mortality
2510	Male	1
	Female	2
2835	Male	1
	Female	4
3160	Male	5
	Female	4

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 is 2760 mg/kg. The test material is therefore classified as Category 5 based on GHS criteria.

Executive summary:

This study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally to 2510, 2835, or 3160 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 3 of 10 animals at the lowest dose level dying. 9 of 10 animals at the highest dose level died. The acute oral LD50 was 2760 mg/kg. The test material is therefore classified as Category 5 based on GHS criteria.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Feb. 1, 1984 To Feb. 21, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

The study examined oral toxicity of the test substance in rats. 5 male and 5 female rats were exposed orally to 1990, 2250 or 2510 mg/kg of test substance and were then monitored for 14 days for mortality and clinical signs.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann
- Weight at study initiation: 111 g female, 121 g male
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Alleindiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 39.8-50.2% in water

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg

Doses:

1990, 2250, 2510 mg/kg test substance

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 (occurrence, nature and duration) and time of death were observed up to 6 hours after treatment and daily thereafter, weighing was performed before treatment and on days 1, 7 and 14 after treatment.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 190 mg/kg bw

Based on:

test mat.

95% CL:

> 2 047 - < 2 343

Mortality:

1990 mg/kg: 2 male animals died within 28 hours, none of the females died
2250 mg/kg: 2 males and 4 females died within 48 hours
2510 mg/kg: 4 males and all females died within 28 hours

Clinical signs:

other: All animals showed signs of toxicity. Symptoms beginning about 30 minutes past application included piloerection, diarrhea, squatting attitude, ataxia, tremor, stagering and slight sedation. These symptoms had disappeared in surviving animals by 72 hours.

Gross pathology:

In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In some of the surviving animals, partial swelling of gastric mucosa and hyperemia of the small intestine was noted and adhesion of stomach, liver, spleen, and peritoneum.

Mortality

Dose (mg/kg)	Sex	Mortality
1990	Male	2
	Female	0
2250	Male	2
	Female	4
2510	Male	4
	Female	5

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 is 2190 mg/kg. The test material is therefore classified as Category 5 based on GHS criteria.

Executive summary:

This study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally to 1990, 2250 or 2510 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 2 of 10 animals at the lowest dose level dying. 9 of 10 animals at the highest dose level died. The acute oral LD50 was 2190 mg/kg. The test material is therefore classified as Category 5 based on GHS criteria.

Reference 7

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Feb. 1, 1984 To Feb. 15, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

The study examined the oral toxicity of the test substance in rats. 5 male and 5 female rats were exposed orally to 1250, 1580 or 1990 mg/kg of test substance and were then monitored for 14 days for mortality and clinical signs.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann
- Weight at study initiation: 102 g female, 108 g male
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Alleindiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12.5-19.9% in water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

1250, 1580, 1990 mg/kg test substance

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 (occurrence, nature and duration) and time of death were observed up to 6 hours after treatment and daily thereafter, weighing was performed before treatment and on days 1, 7 and 14 after treatment.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 600 mg/kg bw

Based on:

test mat.

95% CL:

> 1 455 - < 1 760

Mortality:

1250 mg/kg: 1 male and 1 female animal died within 24 hours
1580 mg/kg: 2 males and 2 females died within 24 hours
1990 mg/kg: 4 males and 4 females died within 48 hours

Clinical signs:

other: All animals showed signs of toxicity. Symptoms beginning about 30 minutes past application included piloerection, diarrhea, squatting attitude, disorders of balance, ataxia and slight sedation. These symptoms had disappeared in surviving animals by 72 ho

Gross pathology:

In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In some of the surviving animals, partial swelling of gastric mucosa and hyperemia of the small intestine was noted along with adhesion of stomach, liver, and spleen.

Mortality

Dose (mg/kg)	Sex	Mortality
1250	Male	1
	Female	1
1580	Male	2
	Female	2
1990	Male	4
	Female	4

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 is 1600 mg/kg.The test material is therefore classified as Category 4 based on GHS criteria.

Executive summary:

This study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally to 1250, 1580 or 1990 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 2 of 10 animals at the lowest dose level dying and 8 of 10 animals at the highest dose level. The acute oral LD50 was 1600 mg/kg. The test material is therefore classified as Category 4 based on GHS criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 080 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(purity of the test material was not noted)

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 402 (Acute Dermal Toxicity), 1981

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

1.0, 2.0 or 4.0 mL/kg bw

No. of animals per sex per dose:

5 animals

Control animals:

no

Details on study design:

Groups of five animals per sex (2-3 kg) were subjected to 24 hours of contact with monoethanolamine (1.0, 2.0, or 4.0 mL/kg bw) which was retained under impervious sheeting on the clipped, intact skin of the trunk. As necessary for larger doses, gauze was wrapped around the trunk over the sample to prevent leakage. Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returned to its cage for the contact period. Doses were varied by adjusting the volume of the test material. After the contact period, excess fluid was removed to diminish ingestion. Observations for toxicity and skin reactions were made at one hour, 7 days, and 14 days after the contact period. Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to termination). LD50 values and the estimated LD50 slopes were calculated by the moving average method (Thompson, 1947; Weil, 1983) and are based on a 14-day observation period. At death or termination, each animal was subjected to a gross pathologic evaluation.

Preliminary study:

The LD50 value for males was 2.46 mL/kg bw (2504 mg/kg bw) with a 95% confidence level of 1.79- 3.39 mL/kg bw (1822 - 3451 mg/kg bw) and a slope of 5.60. The LD50 value for females was 2.83 mL/kg bw (2881 mg/kg bw) with a 95% confidence level of 1.61 - 4.98 mL/kg bw (1639 - 5070 mg/kg bw) and a slope of 3.89.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2.46 - <= 2.83 mL/kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 504 mg/kg bw

95% CL:

> 1 822 - < 3 451

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 881 mg/kg bw

95% CL:

> 1 639 - < 5 070

Mortality:

The numbers of deaths at each dose were as follows:
Dose (ml/kg) Numbers of Animals Dead Time of Death
(M/F)
4.0 5,4 1-2 days
2.0 1,1 2, 13 days
1.0 0,0 N/A
Deaths occurred within two days, except for one female that died at 13 days.

Clinical signs:

other: MALES 4.00 ml/kg dosing group: erythema, edema, necrosis, ecchymosis at 1day; prostration in 1 animal at 1 day. 2.00 ml/kg dosing group: erythema, edema at 1 to 7 days or death; necrosis at 1 to 14 days or death; ecchymosis at 1 day, persisting on 1 to u

Gross pathology:

MALES
4.00 ml/kg dosing group:
lungs salmon-colored; trachea of 1 animal dark red; thymus of 1 animal mottled dark red; large intestines of 1 animal hemorrhaged.

2.00 ml/kg dosing group:
in deceased animal, lungs mottled salmon-colored and bright red; in survivors, lungs bright pink, salmon-colored or mottled bright pink to dark red.

1.00 ml/kg dosing group: lungs of 1 animal dark red.

FEMALES

4.00 ml/kg dosing group:
in deceased animals, lungs salmon-colored to dark red, with dark red foci; thymus of 1 dark red; intestines hemorrhaged; in survivor, nothing remarkable.

2.00 ml/kg dosing group:
in deceased animal, stomach, intestines liquid and gas-filled; small intestines hemorrhaged; in survivors, lungs salmon-colored to red; kidneys of 1 with a pitted surface; intestines of 1 gas-filled.

1.00 ml/kg dosing group:
lungs salmon-colored to dark red, 1animal with dark red foci; stomachs and intestines of 2 animals liquid and/or gasfilled; small intestines of 1 animal hemorrhaged; abdominal cavity of 1 animal liquidfilled.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute dermal (LD50) of 2 -aminoethanol was determined to be in range of 2.46 - 2.83 mL/kg bw in New Zealand White rabbits when applied on the intact skin. LD50 value of 2504 (95% CL: 1822- 3451) mg/kg bw and 2881 (95% CL: 1639 - 5070) mg/kg bw for males and females New Zealand White rabbits, respectively was also determined in this study the test material is therefore classified as Category 5 based on GHS criteria.

Executive summary:

The objective of the study was to determine the acute dermal toxicity of 2-aminoethanol when applied once to the intact rabbit skin.

New Zealand White rabbits weighing between 2 - 3 kg were used in this study. The test material was applied at following three doses (five animals/sex/dose) by adjusting its volume: 1.0, 2.0, or 4.0 mL/ kg bw.

Rabbits were subjected to 24 hours of contact to 2 -aminoethanol retained under impervious sheeting on the clipped and intact skin of the trunk. Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returned to its cage for the contact period. Gauge was also wrapped around the trunk over sample to prevent leakage in case of larger doses. After the contact period, excess fluid was removed to diminish ingestion.

Post treatment, all animals were observed for mortality, clinical signs, skin reactions and body weight changes for 14 days. After 14 days of observation, all surviving animals were euthanized, subjected to necropsy and examined for gross pathological changes.

No mortality was observed at 1.0 mL/kg bw dose. One male within two days and one female at day 13 died at 2.0 mL/kg bw dose while five males and four females died at 4.0 mL/kg bw within two days.

Erythema, edema, necrosis scabs and ulceration were observed in treated animals at 1.0, 2.0, or 4.0 mL/kg bw doses. Apart from these effects, at 1.0 mL/kg bw desquamation was observed in both sexes while abdominal distension, emaciation and audible breathing were also observed in female animals.Animals treated with 2.0 mL/kg bw showed sluggishness (both sexes) along with emaciation (male) and abdominal distention (female). Recovery was observed in survivors at this dose after two days. In high dose group (4.0 mL/kg bw), prostation was obseved in single male along with sluggishness in single female at day 1. One female rabbit also showed recovery after 2 days at high dose.

No abnormal changes in body weight were reported.

In all treated animals, changes in color and texture were observed in multiple internal organs of all animals at all doses. Instances of intestinal hemorrhage were observed in both sexes at high dose and a single instance was also reported in a female at low dose. At high dose, nothing remarkable was observed in the female animals.

Based on the above, the acute dermal (LD50) of 2 -aminoethanol was determined to be in range of 2.46- 2.83 mL/kg bw in New Zealand White rabbits when applined on the intact skin. LD50 value of 2504 (95% CL: 1822 - 3451) mg/kg bw and 2881 (95% CL: 1639 - 5070) mg/kg bw for males and females New Zealand White rabbits, respectively was also determined in this study.

The test material is therefore classified as Category 5 based on GHS criteria.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 402 (Acute Dermal Toxicity), 1981

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CFY (remote Sprague Dawley origin)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Rats were in a weight range of 210 to 239 g prior to dosing on day 1 and approximately six to eight weeks of age. All the rats were acclimated to the experimental environment for a period of 15 days prior to study initiation. Animals were housed in individual metal cages with wire mesh floors. Standard diet and water were provided ad libitum. Each animal was identified by cage number and ear punching.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Test material was a yellow viscous liquid and was applied to an area clipped with electric clippers (approximately 10% of the area) on the backs of 10 rats (five male, five female) at a dose of 2000 mg/kg. The areas were covered with gauze held in place with an impermeable plastic dressing. At the end of 24 hours the dressings were carefully removed and the treated area of skin washed in warm water and blotted dry with absorbent paper.

Duration of exposure:

24 hr

Doses:

2000 mg/kg (undiluted)

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not specified

Details on study design:

Animals were observed soon after dosing and then at frequent intervals for the remainder of day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. The treated areas were examined daily for signs of dermal irritation and assessed according to the standard scoring system for erythema, eschar and oedema. All animals were observed for 14 days after dosing. On day 15 all animals were sacrificed and given a macroscopic post-mortem examination of internal organs.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: undiluted

Mortality:

No mortality was observed exposure to 2000 mg/kg of the undiluted test material.

Clinical signs:

other: There were no signs of systemic reaction. Well defined or slight erythema and slight oedema were observed at all test sites after removal of the occlusive dressings. These reactions were unresolved before progressive hardening of the skin was first detec

Gross pathology:

All terminal autopsy findings were normal.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute lethal dermal dose was found to be greater than 2000 mg/kg.

Executive summary:

The clipped skin on the backs of five male and five female rats were exposed to the test material under an occlusive dressing for 24 hours and observed for another 14 days. Results indicate slight erythema and slight oedema but no acute mortality. The dermal LD50 is > 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute Oral: 

 

Study 1 (C10-13 LAS):

  

An acute oral toxicity study was conducted with C10 -13 LAS, sodium salt in groups of five male and five female rats via oral gavage at 0, 1075, 1220, 1360 or 1710 mg/kg bw, with all doses reported being adjusted from the original for 86% activity. The animals were then monitored for 14 days for mortality, clinical signs and body weight. Mortality was seen at all dose levels, with 4 out of 10 animals at the lowest dose level dying. All animals at the highest dose level died. No effects on body weight were observed. In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In the surviving animals, hyperemia of the stomach was noted, along with abnormalities of the stomach, liver, spleen, kidneys and the peritoneum. Under the study conditions, the acute oral LD50 was 1080 mg/kg bw (Murmann, 1984a).

Study 2 (MEA): 

 

An acute oral toxicity study was conducted with monoethanolamine (MEA) in groups of five male and five female Sprague-Dawley rats at doses of 0, 200, 404, 808, 1010, 1262.5, 1616 and 3232 mg/kg bw via oral gavage. Post treatment, animals were examined for mortality, clinical signs and body weight up to Day 7, following which all surviving animals were euthanized, subjected to necropsy and examined for gross pathological changes. All animals died at the highest dose within 24 h while two males and four females died within 48 h at the next lower dose group. No mortality was observed at other doses. No abnormal gross pathological alterations were observed at the end of 7 days observation period in surviving animals at necropsy. Under the study conditions, the acute oral LD50 was determined to be 1515 mg/kg bw (BASF, 1966).

Study 3 (MEA): 

 

An acute oral toxicity study was conducted with monoethanolamine (MEA) in groups of five male and five female Sprague-Dawley rats at doses of 0, 254, 509, 1018, 2036 and 4072 mg/kg bw via oral gavage. Post treatment, animals were examined for mortality, clinical signs and body weight up to Day 14, following which all surviving animals were euthanized, subjected to necropsy and examined for gross pathological changes. No mortality was observed at the lowest dose. Mortalities observed at higher doses were as follows: 1/10 rats on Day 12, 3/10 within 48 h, 10/10 rats within 4 h and 2/4 rats after 4 h at 509, 1018, 2036 and 4072 mg/kg bw respectively. No abnormal gross pathological alterations were observed at the end of 7 days observation period in surviving animals at necropsy, apart from distended stomach/intestine, reddish fluid in the gastrointestinal tract and mottled appearance of liver. Under the study conditions, the acute oral LD50 was determined to be 1089 mg/kg bw (Myers, 1988).

Study 4 (C10-13 LAS):  

 

An acute oral toxicity study was conducted with C10-13 LAS, sodium salt in groups of five male and five female rats via oral gavage at 0, 2510, 2835 or 3160 mg/kg bw. The animals were then monitored for 14 days for mortality, clinical signs and body weight. Mortality was seen at all dose levels, with 3 out of 10 animals at the lowest dose level dying. 9 out of 10 animals at the highest dose level died. Under the study conditions, the acute oral LD50 was 2760 mg/kg bw (Murmann, 1984b).  

 

Study 5 (C10-13 LAS): 

 

An acute oral toxicity study was conducted with C10-13 LAS, sodium salt in groups of five male and five female rats via oral gavage at 0, 1990, 2250 or 2510 mg/kg bw. The animals were then monitored for 14 days for mortality, clinical signs and body weight. Mortality was seen at all dose levels, with 2 out of 10 animals at the lowest dose level dying. 9 out of 10 animals at the highest dose level died. Under the study conditions, the acute oral LD50 was 2190 mg/kg bw (Murmann, 1984c).  

  

Study 6 (C10-13 LAS): 

 

An acute oral toxicity study was conducted with C10-13 LAS, sodium salt in groups of five male and five female rats via oral gavage at 0, 1250, 1580 or 1990 mg/kg bw. The animals were then monitored for 14 days for mortality, clinical signs and body weight. Mortality was seen at all dose levels, with 2 out of 10 animals at the lowest dose level dying. 8 out of 10 animals at the highest dose level died. Under the study conditions, the acute oral LD50 was 1600 mg/kg bw (Murmann, 1984d).  

  

Study 7 (MEA-LAS): 

  

An acute oral toxicity study was conducted MEA-LAS (40% w/w aqueous solution) in groups of five male and five female Charles River CD rats at dose levels of 0, 950, 1330, 1860 and 2600 mg/kg bw via oral gavage. Animals were observed for mortality, body weight and clinical signs daily for 14 d. The mortality observed in tested groups were as follows: 0/10, 2/10, 8/10 and 10/10 animals died at different dose levels respectively. No abnormalities were noted in any of the test groups upon gross examination at necropsy. Under the study conditions, the acute oral LD50 of MEA-LAS was considered to be 1570 mg/kg bw, based on active ingredient (Nixon, 1970).

 

  

Acute Dermal: 

  

Study 1 (C10-13 LAS): 

 

An acute dermal toxicity study was conducted with C10-13 LAS, sodium salt in five male and five female CFY rats. The test substance was applied to the clipped skin on the back of the rats under an occlusive dressing at a dose of 2000 mg/kg bw for 24 h. At the end of exposure period, following removal of the dressings the skin was washed with warm water and the exposed skin was observed for 14 days. On Day 15, all animals were sacrificed, and a macroscopic examination of internal organs were performed. No mortality was observed. The exposed skin revealed slight erythema and slight oedema. Under the study conditions, the acute dermal LD50 was determined to be greater than 2000 mg/kg bw (Kynoch, 1986).   

 

Study 2 (MEA): 

 

An acute dermal toxicity study was conducted with monoethanolamine (MEA) in five male and five female New Zealand White rabbits. The test substance was applied to the clipped skin on the back of the rabbits under an occlusive dressing at doses of 0, 1, 2 and 4 mL/kg bw for 24 h. At the end of exposure period, following removal of the dressings the skin was washed with warm water. Post treatment, all animals were observed for mortality, clinical signs, skin reactions and body weight changes for 14 days. After 14 days of observation, all surviving animals were euthanized, subjected to necropsy and examined for gross pathological changes. No mortality was observed at 1 mL/kg bw, while 2/10 rabbits at 2 mL/kg bw by Day 13 and 9/10 rabbits died at 4 mL/kg bw by 48 h. The exposed skin revealed erythema, oedema, necrosis, scabs and ulceration at all doses. Under the study conditions, the acute dermal LD50 was determined to be in the range of 2.46-2.83 mL/kg bw (equivalent to 2504 and 2881 mg/kg bw for male and female rabbits respectively) (Myers, 1988).

Justification for classification or non-classification

The acute oral and dermal toxicity of the dissociation products of MEA-LAS (MEA and LAS) have been studied as well as the acute oral toxicity of MEA-LAS itself. The lowest acute oral toxicity value (1080 mg/kg bw) was for C10-13LAS, sodium salt, while that for MEA-LAS was 1570 mg/kg bw. Acute dermal toxicity values for both LAS and MEA were in excess of 2000 mg/kg bw.Based on these results, MEA-LAS warrants classification as Acute Tox 4 – H302 (harmful if swallowed) according to EU CLP (1272/2008/EC) criteria.