Amides, C12-18(even-numbered) and C18(unsatd.), N-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:

February 17 1988 to April 03 1988

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

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Bor:WISW (SPF TNO)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, 4799 Borchen, Germany
- Average weight at study initiation: 119 g
- Housing: Macrolon type III cages, 1-5 animals/cage
- Diet (e.g. ad libitum): R10 diet for rats, Ssniff special feed, 4770 Soest, Germany
- Water (e.g. ad libitum): tap water
- Acclimation period: 4 - 8 d
- Fasting period before test begin: 16 h

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

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% test substance in corn oil
- Amount of vehicle (if gavage): 15 cm3/kg bw

Doses:

3000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: pre-dose, Days 1, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

None.

Clinical signs:

other: None.

Gross pathology:

No effect of the test substance.

Table 1: Bodyweight evolution (average weight) in g

Dose (mg/kg bw)	Pre-dose (fasted)	24 h	Week 1	Week 2	Bodyweight gain
3000	119.0	127.1	160.6	190.2	71.9

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 was determined to be >3000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. MEA (100% active), to Bor:WISW (SPF TNO) rats according to OECD Guideline 401. Male and female rats were gavaged once with the read across substance in corn oil at 3000 mg/kg bw and observed during 14 d for clinical signs, mortality and bodyweight evolution. Gross pathology was conducted on all animals at termination. There were no clinical signs and no mortality during the study. Bodyweight evolution remained within expected values. No macroscopic changes in the organs were observed at test end. Under the study conditions, the LD50 was determined to be >3000 mg/kg bw (Mürmann, 1988). Based on the results of the read across study, a similar LD50 value is expected for the test substance.

Reference 2

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 4, 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)

Version / remarks:

1987

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: Males - 152 - 182 g, females - 140-156 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 (%): 44-65
- Air changes (per h): 15
- Photoperiod (h dark/h light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg in both range-finding and main study

No. of animals per sex per dose:

One in range-finding study and five in main study

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.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality.

Clinical signs:

other: No signs of systemic toxicity.

Gross pathology:

No abnormalities noted at necropsy.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a solution in arachis oil BP at a dose level of 2000 mg/kg bw. The animals were observed for 14 d after dosing and were then killed and subjected to gross pathological examination. There was no mortality in the study and no signs of systemic toxicity were noted. All animals showed an expected gain in body weight apart from one female which showed reduced body weight gain during the second week. No abnormalities were noted at necropsy. Under the study conditions, the LD50 was determined to be >2000 mg/kg bw (Hempstock, 1996).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Quality of whole database:

Sufficient data is available to evaluate this endpoint.

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:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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

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.

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.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

A limit test was conducted to determine the acute dermal toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to albino rabbits. Three male and three female rabbits were administered a single dose of the read across substance at a level of 2000 mg/kg bw. Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two males and one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the read across 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 exposure period, the sleeve was removed and the skin sites gently cleansed. All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior. All animals survived and appeared normal through to Day 14. Two females that had abraded skin lost weight over the 14 d post-exposure period. All remaining rabbits gained weight. Under the study conditions, the acute dermal LD50 was determined 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 information is available on read-across substance.

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a solution in arachis oil BP at a dose level of 2000 mg/kg bw. The animals were observed for 14 d after dosing and were then killed and subjected to gross pathological examination. There was no mortality in the study and no signs of systemic toxicity were noted. All animals showed an expected gain in body weight apart from one female which showed reduced body weight gain during the second week. No abnormalities were noted at necropsy. Under the study conditions, the LD50 was determined to be >2000 mg/kg bw (Hempstock, 1996).

A study was conducted to determine the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to Bor:WISW (SPF TNO) rats according to OECD Guideline 401. Male and female rats were gavaged once with the read across substance in corn oil at 3000 mg/kg bw and observed during 14 d for clinical signs, mortality and bodyweight evolution. Gross pathology was conducted on all animals at termination. There were no clinical signs and no mortality during the study. Bodyweight evolution remained within expected values. No macroscopic changes in the organs were observed at test end. Under the study conditions, the LD50 was determined to be >3000 mg/kg bw (Mürmann, 1988).

Dermal

A limit test was conducted to determine the acute dermal toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to albino rabbits. Three male and three female rabbits were administered a single dose of the read across substance at a level of 2000 mg/kg bw. Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two males and one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the read across 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 exposure period, the sleeve was removed and the skin sites gently cleansed. All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior. All animals survived and appeared normal through to Day 14. Two females that had abraded skin lost weight over the 14 d post-exposure period. All remaining rabbits gained weight. Under the study conditions, the acute dermal LD50 was determined to be >2000 mg/kg bw (Palanker, 1976).

Justification for classification or non-classification

 The available data for the read across substance C8-18 and C18-unsatd. MEA indicates a low potential for acute toxicity (oral and dermal LD50 >2,000 mg/kg bw). The substance therefore does not meet the requirement for classification according to CLP (EC 1272/2008) criteria.