N,N-dimethyl-alkyl-1-amines, reaction products with alkali hydroxide and chloroacetic acid

Endpoint summary

Description of key information

oral (OECD 401): LD50mouse = 2640 mg/kg bw (neat substance); LD50rat = 3202.5 mg/kg bw (calculated from 3 mL/kg bw with a density of 1.0675 g/cm³)
dermal (OECD 402 limit test): LD50rat > 2000 mg/kg bw (31% a.i.)

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: Comparable to guideline study with acceptable restrictions. Limited documentation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limited documentation

Principles of method if other than guideline:

Study performed before actual guideline was established.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: range 59 - 86 g
- Fasting period before study: overnight

Route of administration:

oral: gavage

Vehicle:

other: unchanged and water, respectively

Details on oral exposure:

- Amount of vehicle (if gavage): 0, 1.6, 2.5, 3.2, 4.0, 5.0, 8.0 ml/kg bw of test substance (aqueous solution)
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw (in the report stated as minimum volume-dosage, which very likely must be a typing error)

Doses:

0, 1.6, 2.5, 3.2, 4.0, 5.0, 8.0 ml/kg bw (approximately equivalent to mg/kg bw)

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: observations several times on the day of application; weighing at dosing and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, time to death, clinical signs, body weight

Statistics:

From the mortality data the LD50 value and its 95 % confidence limits were calculated by the method of Litchfield and Wilcoxon (1949).

Preliminary study:

Range finder with 1 animal per sex and dose at dosages of 0, 5.0 and 10 ml/kg bw indicated a median lethal dose (LD50) in the region of 5 ml/kg bw. Subsequently dosing was extended to groups of 5/sex/dose in order to locate the LD50 more precisely.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 202.5 mg/kg bw

Based on:

test mat.

95% CL:

2 775.5 - 3 629.5

Remarks on result:

other: calculated from 3 mL/kg bw based on the density of 1.0675 g/cm³

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 mL/kg bw

Based on:

test mat.

95% CL:

2.6 - 3.4

Mortality:

Males:
8.0 ml/kg: 5/5 (after 5 - < 22 h)
5.0 ml/kg: 5/5 (after 5 - < 22 h)
4.0 ml/kg: 5/5 (after < 21 h)
3.2 ml/kg: 2/5 (after < 22 h)
2.5 ml/kg: 0/5
1.6 ml/kg: 0/5
control: 0/5

Females:
8.0 ml/kg: 5/5 (after < 22 h)
5.0 ml/kg: 5/5 (after < 22 h)
4.0 ml/kg: 4/5 (after < 21 h)
3.2 ml/kg: 4/5 (after < 22 - 24 h)
2.5 ml/kg: 2/5 (after < 23 - 27 h)
1.6 ml/kg: 0/5
control: 0/5

Clinical signs:

other: Lethargy and diuresis were observed at dosages of 3.2 ml/kg bw or more. Death was preceded by ataxia and coma and usually occurred within 5 to 27 hours following dosing. Recovery of the survivors was apparently complete five days after dosing, as judged

Gross pathology:

The deceased animals showed inflammation of the intestines which were devoid of solid content. The autopsies of the survivors revealed no treatment-related findings.

Conclusion:

The findings in the deceased animals demonstrate mortality due to local irritant effects in form of gastro-intestinal inflammation rather than systemic toxicity. According to the criteria of the DSD and the CLP regulation the substance does not have to be classified for acute oral toxicity.

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified
DSD: not classified

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:

other: Study meets generally accepted scientific principles, acceptable for assessment. Only very limited documentation, only 5 days observation period.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Only very limited documentation, only 5 days observation period

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

CF-1

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Weight at study initiation: 18 - 21 g
- Fasting period before study: no data
- Housing: 5/cage
- Diet (e.g. ad libitum): Lab Blox, ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 % (test material was diluted 1:3 in water just prior to the test)

Doses:

6670, 8350, 10000 mg/kg bw

No. of animals per sex per dose:

10 (sex not specified)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Necropsy of survivors performed: no data

Statistics:

Oral LD50 was calculated according to the method of Litchfield and Wilcoxon (1949).

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 640 mg/kg bw

Based on:

act. ingr.

95% CL:

2 310 - 3 000

Remarks on result:

other: recalculated to neat substance

Sex:

not specified

Dose descriptor:

LD50

Effect level:

8 800 mg/kg bw

Based on:

test mat.

95% CL:

7 700 - 10 000

Mortality:

10000 mg/kg: 7/10
8350 mg/kg: 4/10
6670 mg/kg: 1/10

Clinical signs:

other: not reported

Gross pathology:

not reported

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified
DSD: not classified

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment Only one animal/dose

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

insufficient documentation, only one animal/dose

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Chr-CD

Sex:

male

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: aqueous solution of 60% of original substance (25% active ingredient as sodium salt in aqueous solution) for 3400, 5000, 7500, 11000 and 17000mg/kg bw and 20 % of original substance (25% active ingredient as sodium salt in aqueous solution) for 670 and 2250mg/kg bw
- Amount of vehicle (if gavage): no data

Doses:

670, 2250, 3400, 5000, 7500, 11000, 17000 mg/kg bw

No. of animals per sex per dose:

1

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

male

Dose descriptor:

other: approx. LD100

Effect level:

7 500 mg/kg bw

Mortality:

Animals that received 17000, 11000 and 7500 mg/kg bw died within 2 days, lower dosed animals survived to the end of the observation period

Clinical signs:

other: At lethal doses: severe weight loss, diarrhea, bloody discharge from nose and mouth at death; at non-lethal doses: weight loss, diarrhea and increased water intake

The approx. LD100 for N-Lauryl Betaine as a solution of the sodium salt was 7500 mg/kg bw in male rats.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LD50

Remarks:

mouse

Effect level:

2 640 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 2 310 - < 3 000

Remarks on result:

other: recalculated to neat substance. CAS 68424-94-2

Sex:

not specified

Dose descriptor:

LD50

Remarks:

mouse

Effect level:

8 800 mg/kg bw

Based on:

test mat.

95% CL:

>= 7 700 - <= 10 000

Remarks on result:

other: CAS 68424-94-2

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

3 202.5 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 775.5 - <= 3 629.5

Remarks on result:

other: calculated from 3 mL/kg bw based on the density of 1.0675 g/cm³. CAS 931-700-2

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

3 mL/kg bw

Based on:

test mat.

95% CL:

>= 2.6 - <= 3.4

Remarks on result:

other: CAS 931-700-2

Sex:

male

Dose descriptor:

LD100

Remarks:

rat

Effect level:

ca. 7 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: CAS 683-10-3

Sex:

male

Dose descriptor:

LD50

Remarks:

rat

Effect level:

71 mg/kg bw

Based on:

test mat.

95% CL:

52 - 96

Remarks on result:

other: CAS 683-10-3

Remarks:

disregarded study

Sex:

female

Dose descriptor:

approximate LD50

Remarks:

rat

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: CAS 683-10-3

Remarks:

disregarded study

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for Betaines, C12-14 (even numbered)-alkyldimethyl, potassium salt; aqueous commercial product(s) is estimated to be 2640 mg/kg bw.

Executive summary:

Several studies are available from structural analogues CAS 68424 -94 -2, EC 931 -700 -2 and 683 -10 -3. The LD50 for Betaines, C12-14 (even numbered)-alkyldimethyl, potassium salt; aqueous commercial product(s) was estimated to be 2640 mg/kg bw from the most sensitive study. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in the oral LD50 that are higher than the typical experimental error of the test method.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Original reference not available.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Remarks:

Kashima Laboratory, Mitsubishi Chemical Safety Institue Ltd., 14 Sunayama, Kamisu-shi, Ibaraki, 314-0255, Japan

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nihon Charles River
- Age at study initiation: 8 weeks
- Weight at study initiation: 182-203 g ± 20%
- Fasting period before study: 18 hours before and 3 hours after
- Housing: polycarbonate cages (265W x 426D x 200H mm)
- Diet (ad libitum): MF Oriental
- Water (ad libitum): filtered (5 μm) and ultra-violet radiated
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 - 22.8
- Humidity (%): 43.1 - 69.3
- Air changes (per hr): 6 - 20
- Photoperiod (hrs dark / hrs light): 12 / 12 (7.00 - 19.00 light on)

Route of administration:

oral: gavage

Vehicle:

other: water for injection

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


CLASS METHOD
- Rationale for the selection of the starting dose: Material Safety Data Sheet and RTECS (Registry of Toxic Effects of Chemical Substances)

Doses:

300 mg/kg (1st and 2nd steps) and 2000 mg/kg (3rd step)

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily; weighing on days 1, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, body weight gain

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 300 - 2 000 mg/kg bw

Mortality:

All animals receiving 2000 mg/kg died within 2 days of the administration. No mortality was observed in the 300 mg/kg group.

Clinical signs:

other: Clinical signs appeared approximately 30 minutes after application of the test substance. Decrease in locomotor activity, irregular respiration, loose stool, and soiled perineal regions were noted before death. No clinical signs were observed in the 300 m

Gross pathology:

At necropsy, distention of the stomach or small intestine, reddening of the glandular stomach epithelium, abnormal contents of the small intestine, hemorrhage in the thoracic cavity, and red ascites in the abdominal cavity were noted in dead animals.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: acute oral 4, H302
DSD: Xn, R22

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment. Dose levels not specified.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

dose levels not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: 200 - 250 g
- Fasting period before study: yes, overnight
- Acclimation period: 5 days

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 % (w/v)

Doses:

4 dose levels, not further specified

No. of animals per sex per dose:

5 males

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: no data
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 values were calculated using the moving average method (Thompson, 1947). Comparison between datasets, where appropriate, used Student's t test.

Sex:

male

Dose descriptor:

LD50

Effect level:

71 mg/kg bw

95% CL:

52 - 96

Clinical signs:

other: sluggishness, diarrhea, and lacrimation in some animals

Gross pathology:

Deceased animals showed distension of the gastrointestinal tract with red fluid, the lungs appeared mottled and red.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 640 mg/kg bw

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2-4) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on structural and physico-chemical similarities (refer to endpoint discussion for further details). Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

Study period:

1987-07-27 to 1987-08-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CD (Crl:COBS CD(SD)BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, England
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: 200 to 232 g
- Fasting period before study: no
- Housing: individually housing in metal cages with wire mesh floors
- Diet: ad libitum, standard laboratory rodent diet "Labsure LAD 1"
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day prior to treatment hair was removed from the dorsolumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used.

The test substance was applied by spreading it evenly over the prepared skin. Total volume applied was 1.92 ml/kg bw. Test substance was applied in the original state (aqueous solution, a.i. 31 %) as delivered by the sponsor. The treated area was then promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.

At the end of the 24-hours exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30°-40°C) water and blotting dry with absorbent paper.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw (based on product),

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Body weights were recorded on Day 1 (day of dosing), 8 and 15
- Clinical observation: Animals were observed soon after dosing and 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. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation. The nature, severity, approximate time of
onset and duration of each toxic sign.
- Necropsy of the survivors performed: yes
- Other examinations performed: skin reactions - The treated areas of skin were examined daily for signs of dermal irritation and assessed according to the following arbitrary scoring system.
Erythema and eschar formation:
No erythema = score 0
Slight erythema = score 1
Well-defined erythema = score 2
Moderate to severe erythema = score 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) = score 4
Oedema formation:
No oedema = score 0
Slight oedema = score 1
Well-defined oedema (area well-defined by definite raising) = score 2
Moderate oedema (raised approximately 1 millimetre) = score 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) = score 4
A separate record was kept of dermal changes other than erythema and oedema.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: based on product

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 620 mg/kg bw

Remarks on result:

other: based on a.i.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: based on product; mortality 0/10

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 620 mg/kg bw

Remarks on result:

other: based on a.i.; mortality 0/10

Mortality:

0/10

Clinical signs:

other: - Application site: Sites of application of the test substance showed slight or well-defined erythema in all animals on Day 2 and/or 3. On Day 4 and Day 5, slight erythema were seen in three male and four female rats, sloughing in two male rats and one fe

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified
DSD: not classified

Executive summary:

In an acute dermal toxicity study according to EU Method B.3 and OECD Guideline 402, 5 male and 5 female CD rats (Crl:COBS CD(SD)BR) were dermally exposed to Coco AAPB (a.i 31 %) as delivered by the sponsor for 24 hours to 10% of total body surface at a dose of 2000 mg/kg bw (limit test). Test sites were covered with an occlusive dressing. After 24 hours, the test sites were rinsed with warm water. Animals then were observed for 14 days after dosing.

There were no clinical signs of systemic reaction to treatment. Sites of application of the test substance showed slight or well-defined erythema in all animals on Day 2 and/or 3. On Day 4 and Day 5, slight erythema were seen in three male and four female rats, sloughing in two male rats and one female rat and hyperkeratinisation in three female rats. All skin reactions were completely reversible by Day 6 in all animals. Slightly low bodyweight gains were recorded for three females on Day 8. All other rats achieved anticipated bodyweight gains throughout the study. Terminal autopsy findings were normal.

Dermal LD₀ Combined: 2000 mg/kg bw

Dermal LD₅₀ Combined: > 2000 mg/kg bw

LD₀ and LD₅₀ determined refer to the test substance as delivered by the sponsor. Amount of active ingredient in test substance is 31 %. Therefore the calculated oral LD₀and LD₅₀ combined referring to 100 % active substance is 620 and > 620 mg/kg bw, respectively.

Coco AAPB (a.i. 31 %) is of low toxicity based on the LD₅₀ in males and females.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: based on product

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 620 mg/kg bw

Remarks on result:

other: based on a.i.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: based on product; mortality 0/10

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 620 mg/kg bw

Remarks on result:

other: based on a.i.; mortality 0/10

Mortality:

0/10

Clinical signs:

other: - Application site: Sites of application of the test substance showed slight or well-defined erythema in all animals on Day 2 and/or 3. On Day 4 and Day 5, slight erythema were seen in three male and four female rats, sloughing in two male rats and one fe

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

An dermal LD50 greater than 2000 mg/kg bw was estimated for Betaines, C12-14 (even numbered)-alkyldimethyl, potassium salt; aqueous commercial product(s).

Executive summary:

One study is available from the structural analogue CAS 61789 -40 -0. The LD50 for Betaines, C12-14 (even numbered)-alkyldimethyl, potassium salt; aqueous commercial product(s) was estimated to be greater than 2000 mg/kg bw from this study. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in the oral LD50 that are higher than the typical experimental error of the test method.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural and physico-chemical similarities (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

There is no data available on the acute toxicity of N,N-dimethyl-alkyl-1-amines, reaction products with alkali hydroxide and chloroacetic acid. However, there is reliable data for the structural related substances CAS 68424-94-2, CAS 683-10-3, EC 931-700-2 and CAS 61789-40-0. The target substance and the source substances show pronounced structural and physico-chemical similarities. Therefore, read-across was performed based on an analogue approach. For a detailed justification of the analogue approach, please refer to section 13 of the technical dossier.

Two reliable studies are available addressing acute oral toxicity, the first one performed with undiluted EC 931-700-2 in rats (Huntingdon Research Centre, 1969) and the second one with an undiluted aqueous solution containing 30% a.i. of CAS 68424-94-2 in mice (Levenstein, 1979). The most sensitive one was the study with CAS 68424-94-2, demonstrating an LD50 of 2640 mg/kg bw, recalculated to neat substance, in mice. With EC 931-700-2 a LD50 of 3202.5 mg/kg bw was demonstrated in rats. The mortality observed in this study had to be attributed to local irritant effects of the test substance, manifesting in form of gastro-intestinal inflammation in the deceased animals only, rather than systemic toxicity. Both values were in the same range of magnitude. Therefore, 2640 mg/kg bw was adopted as oral LD50 as the most sensitive value. The values are also in line with an approximate LD100 of 7500 mg/kg bw reported for CAS 683-10-3 by the supporting study (Haskell Laboratory, 1963). Further information for that substance is available from a secondary source reporting a result derived from the acute toxic class method (Kashima Laboratory, 2005). In this study a classification into acute toxicity class 4 (LD50 >300 - 2000 mg/kg bw) was derived. The original data source was not available, therefore it was not chosen for assessment. Additionally, an LD50 of 71 mg/kg bw is reported in a publication (Ridout et al., 1991). Although being the lowest value in the range this publication was not chosen for assessment. First of all it suffers from extremely limited documentation, as even dose levels were not reported, and secondly the value is extraordinarily low in comparison with any other available data, which lacks a logical explanation. Therefore, this publication was not suitable for assessment.

For acute dermal toxicity, read-across data from cocamidopropyl betaine (CAS 61789-40-0) is used (Kao, 1987). This study was designed as a limit test with application of 2000 mg/kg bw of an aqueous solution with 31% active ingredient (commercial product, as supplied) to the skin of rats for a period of 24 hours under occlusive conditions. No mortality occurred, and no clinical signs were observed within the 14-day observation period. There were no unusual findings at terminal autopsy; the only observations were signs of slight to well-defined local skin irritation at the application sites. Therefore, an LD50 > 2000 mg/kg bw was established for the commercial product with 31% active ingredient, the dermal LD50 for 100% active substance was calculated to be > 620 mg/kg bw.

However, although the read-across study conducted with CAS 61789-40-0 does not cover the limit dose requested by OECD guideline 402, carrying out additional acute dermal studies for the pure substances is scientifically not justified as the test substance is assumed to be corrosive at concentrations greater than 30% based on experimental data and on a worst case assumption.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the analogue substances do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.