Amides, coco, N,N-bis(hydroxyethyl); C10-12 and C18-unsatd. DEA

Endpoint summary

Description of key information

Based on the results of the read across study, the oral and dermal LD50 value for test substance, C10-12 and C18-unsatd. DEA is considered to be >2000 mg/kg bw.

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Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

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 section 13 for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

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:

2,000 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

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

No abnormalities noted at necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 in rat 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 401and 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 oral LD50 in rat was >2000 mg/kg bw (Hempstock, 1996). Based on the results of the read across study, similar oral LD50 can be considered for the test substance, C10-12 and C18-unsatd. DEA.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline compliant study

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:

Reason / purpose for cross-reference:

data waiving: supporting information

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:

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

Adequacy of study:

supporting study

Study period:

Not available

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 section 13 for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

not specified

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:

TEST ANIMALS
- Weight at study initiation: 1.9 to 2.7 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap if used: The trunk of each animal was encased in a sleeve of plasticized material after application of test material

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Three animals with abraded skin and three animals with intact skin

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 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 behavior for 14 d

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were observed.

Clinical signs:

other: All animals appeared normal throughout the 24 h exposure period and the 14 d post-exposure observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the dermal LD50 in rat 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 albino rabbit. 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 rat was found to be > 2000 mg/kg bw (HPVIS, 1976). Based on the results of the read across study, a similar dermal LD50 can be considered for the test substance,C10-12 and C18-unsatd. DEA.

Reference 2

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Published study meeting generally accepted scientific standards

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 401and 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 oral LD50 in rat was >2000 mg/kg bw (Hempstock, 1996).Based on the results of the read across study, similar oral LD50 can be considered for the test substance,C10-12 and C18-unsatd. DEA.

Dermal:

As per Annex VIII 8.5.3 of the REACH regulation, the acute dermal toxicity testing is not needed as the substance does not meet the criteria for classification for acute toxicity and STOT SE for the oral route. This is also supported by the absence of any systemic effects in the in vivo skin sensitisation study available with the read across substance, C8-18 and C18-unsatd. DEA. Moreover, given the physico-chemical properties of the test substance, the dermal LD50 value is less likely (due to lower absorption potential of dermal route) to be lower than oral LD50 or the oral doses showing clinical signs. This can be further supported by low acute dermal toxicity conclusion drawn for the read across substance, based on >2000 mg/kg bw dermal LD50 value, available from a study published in HPVIS (2001). Hence, testing via dermal route will less likely result in any additional hazard identification and testing is therefore considered unnecessary.

Inhalation:

Due to the low vapour pressure and high viscosity of the test substance, inhalatory exposure is not expected to occur under the conditions of normal and foreseeable handling and use and therefore additional testing for acute inhalation toxicity is not considered necessary. Moreover, because the substance is irritating to skin and highly irritating to eyes, the required risk reduction measures are already in place to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

Justification for classification or non-classification

Based on the results of the read across studies (i.e., oral LD50 >2000 mg/kg bw and absence of systemic effects in skin sensitisation study), the test substance, C10-12 and C18-unsatd. DEA, is concluded not to warrant classification for acute oral or dermal toxicity, according to the EU CLP criteria (Regulation 1272/2008/EC).