Amides, C12-18 and C18-unsatd., N,N-bis(hydroxyethyl)

Endpoint summary

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:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From February 20, 1996 to April 11, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the section 13 for details on the category justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 5-8 wk
- Weight at study initiation: 152-174 g
- Fasting period before study: Overnight
- Housing: Groups of up to five by sex in solid-floor polypropylene cages
- Diet: Rat and mouse expanded diet no. 1, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Atleast 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 39-65
- Air changes (per h): 15
- Photoperiod (h dark/h light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.99 mL/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of clinical observation: 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 d
- Frequency of weighing: On Days 0, 7 and 14
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination

Statistics:

None

Preliminary study:

No deaths or clinical signs of toxicity were observed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: None

Mortality:

No mortality

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

No abnormalities noted at necropsy

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 in rats was >2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. DEA, in Sprague-Dawley CD rats according to OECD Guideline 401 and EU Method B1, in compliance with GLP. A group of 10 fasted animals (five males and five females) was administered a single oral dose of test substance at a dose level of 2000 mg/kg bw. The animals were observed for 14 d after dosing, then sacrificed and subjected to gross pathological examination. No mortalities and no signs of systemic toxicity were observed during the study. All animals showed expected gain in body weight. No abnormalities were observed at necropsy. Under the study conditions, the LD50 in rats was >2000 mg/kg bw (Hempstock, 1996).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

From October 8, 1985 to October 23, 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

Refer to the section 13 for details on the category justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mollegaard Breeding Centre Ltd, Ejby, DK-4623 LI. Skensved.
- Weight at study initiation: 148±3 g
- Fasting period before study: 18 h
- Housing: Housed in Macrolone cages Type III (42x26x15 cm) in groups of 2 or 3 per cage (males and females separated)
- Diet: Complete rodent diet - Altromin 1314, ad libitum
- Water: Drinking water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: No acclimatization as the rats were born in the laboratory and had been kept in the same environment during the experiment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±2
- Humidity (%): 55±15
- Air changes (per h): 10
- Photoperiod: 6-18 h of light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Maximum dose volume applied: 5 mL/kg

Rationale for the selection of the starting dose: A range-finding study was conducted, which indicated that LD50 would exceed 5,000 mg/kg (details not reported)

Doses:

5000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of clinical observations: 1, 3 and 6 h after administration and daily thereafter once or twice for 14 d
- Frequency of weighing: Day 0, 7 and 14
- Necropsy of survivors performed: Yes

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: Sedation and piloerection were observed in all the rats shortly after treatment. All rats recovered completely by Day 2, except for one female, which showed pilorection till Day 7. This rat also showed pinched abdomen on Days 4, 5 and 6.

Gross pathology:

No macroscopic organ changes were observed, except for one rat (same animal which showed low body weight gain), in which the kidneys were presented with enlarged size, plumpy shape and light and pale tissue on macroscopic observation.

Other findings:

None

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 in rats was >5000 mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. DEA, in Wistar rats according to OECD Guideline 401. A group of 10 fasted animals (five males and five females) was given a single oral dose of test substance at a dose level of 5000 mg/kg bw. The animals were observed for 14 d after dosing, then sacrificed and subjected to gross pathological examination. Clinical signs such as sedation and piloerection were observed in all animals following gavage, with recovery by Day 2. There were no macroscopic changes in the organs at necropsy. No mortality was observed in either sex. Under the study conditions, the LD50 in rats was >5000 mg/kg bw (Skydsgaard, 1985).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient good quality data available.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Refer to the section 13 for details on the category justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: A modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration.

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 1.9-2.7 kg

No further information avaialble.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two male, one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the test substance through the stratum corneum. After test substance application the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the 24 h exposure period the sleeve was removed and the skin sites gently cleansed.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Details on study design:

All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortalities observed.

Clinical signs:

other: All animals appeared normal through Day 14.

Gross pathology:

Not evaluated.

Other findings:

Not evaluated.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the acute dermal LD50 in rabbits was found to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the read across substance, C8-18 and C18-unsatd. DEA, in male/female New Zealand White rabbits. The procedure was the modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration. A single dose of 2000 mg/kg bw of test substance was applied to the abraded and intact skin of the test animals. The trunk of each animal was then encased in a sleeve of plasticized material for a 24 h period. Animals were observed immediately after dosing, and at 1, 6 and 24 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, skin response and general behaviour for 14 d. No mortality occurred. All animals appeared normal throughout the 24 h exposure and 14 d post-exposure observation periods. Under the study conditions, the dermal LD50 in rabbits was found to be > 2000 mg/kg bw (Palanker, 1976).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient data available.

Additional information

Oral

A study was performed to assess the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. DEA, in Sprague-Dawley CD rats according to OECD Guideline 401 and EU Method B1, in compliance with GLP. A group of 10 fasted animals (five males and five females) was administered a single oral dose of test substance at a dose level of 2000 mg/kg bw. The animals were observed for 14 d after dosing, then sacrificed and subjected to gross pathological examination. No mortalities and no signs of systemic toxicity were observed during the study. All animals showed expected gain in body weight. No abnormalities were observed at necropsy. Under the study conditions, the LD50 in rats was >2000 mg/kg bw (Hempstock, 1996).

A study was performed to assess the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. DEA, in Wistar rats according to OECD Guideline 401. A group of 10 fasted animals (five males and five females) was given a single oral dose of test substance at a dose level of 5000 mg/kg bw. The animals were observed for 14 d after dosing, then sacrificed and subjected to gross pathological examination. Clinical signs such as sedation and piloerection were observed in all animals following gavage, with recovery by Day 2. There were no macroscopic changes in the organs at necropsy. No mortality was recorded in either sex. Under the study conditions, the LD50 in rats was >5000 mg/kg bw (Skydsgaard, 1985).

Dermal

A study was conducted to determine the acute dermal toxicity of the read across substance, C8-18 and C18-unsatd. DEA, in male/female New Zealand White rabbits. The procedure was the modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration. A single dose of 2000 mg/kg bw of test substance was applied to the abraded and intact skin of the test animals. The trunk of each animal was then encased in a sleeve of plasticized material for a 24 h period. Animals were observed immediately after dosing, and at 1, 6 and 24 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, skin response and general behaviour for 14 d. No mortality occurred. All animals appeared normal throughout the 24 h exposure and 14 d post-exposure observation periods. Under the study conditions, the dermal LD50 in rabbits was found to be > 2000 mg/kg bw (Palanker, 1976).

Justification for classification or non-classification

The available data on the read across substance C8-18 and C18-unsatd. DEA indicates a low potential for acute toxicity (oral and dermal LD50s >2000 mg/kg bw). The test substance therefore does not meet the requirement for classification according to CLP (EC 1272/2008) criteria.