Fatty acids, rape-oil, hydrogenated, reaction products with diethylenetriamine, di-Me sulfate-quaternized

Endpoint summary

Description of key information

Based on the results of the read across study as well as a study with the test substance, 'di-C18-22 AAEMIM-MS' is considered to be of low acute toxicity through acute oral and dermal routes.

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 October 03, 2007 to October 10, 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA study

Justification for type of information:

Refer to section 13 of IUCLID 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HanRcc: WIST(SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 11 weeks
- Weight at study initiation: 165.1 - 186.2 9 at day of application
- Fasting period before study: for approximately 17 to 18 h (access to water was permitted). Food was provided again approximately 3 h after dosing
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland)
- Diet: ad libitum; pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 23/07 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland)
- Water: ad libitum; community tap water from Füllinsdorf
- Acclimation period: 6 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 -70 %
- Air changes (per hr): 10-15 air changes per h
- Photoperiod (hrs dark / hrs light): the Iightening was in a 12-h Iight/dark-cycle.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Maximum dose volume applied: 2000 mg/kg body weight

Doses:

Dose levels: 2000 mg/kg body weight
Concentrations: 0.2 g/mL
Dosing: one single application by gavage
Dosing volume: 10 mL/kg bw
The test substance was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).
Afterwards, the test substance preparation was warmed up to 50°C. The formulations were prepared using a suitable homogenizer. The test substance preparation was kept at room temperature for cooling and was administered when a temperature between 20°C and 30°C is reached. The temperature was measured before treatment with a thermometer and reached 24°C and 25.8°C.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
- Frequency of observations and weighing:

- Mortality / Viability and Clinical Signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15. All abnormalities were recorded.

- Body Weights: On test days 1 (prior to administration), 8 and 15.

Statistics:

No statistical analysis was used.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

No animal died

Remarks on result:

other: No animal died

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the study conditions, the acute oral LD50 of the test substance in rats was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read substance, 'di-C16-18 and C18-unsatd. AAEMIM-MS', according to OECD Guideline 423 (Acute Toxic Class Method), in compliance with GLP. Three FemaleHanRcc: WIST(SPF)rats were administered the test substance by oral gavage at a dose of 2000 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. There was no mortality in this study. No evidence of systemic toxicity was noted during the study period. No toxicologically significant effects on bodyweight were recorded during the study period and no abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw (Arcelin, 2010). Based on the results of the read across study, similar oral LD50 value can be expected for the test substance, 'di-C18-22 AAEMIM-MS'.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good quality 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:

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:

experimental study

Adequacy of study:

key study

Study period:

From May 11, 2010 to May 25, 2010

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

GLP compliance:

yes

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:

Source: Covance Research Products, Inc., Denver
Acclimation: 7 days
Body weights: 2.6 - 3.0 kg for males and 2.9 - 3.3 kg for females
Diet: Fresh PMI Rabbit Chow
Water: ad libitum
Light changes: 12h / 12h

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

To obtain a paste

Details on dermal exposure:

10% of the total body surface (clipped free of hair)
Amount: 3.5 mL

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The test substance was kept in contact with the skin for 24 h. Dermal responses at test sites were recorded at 24 h postdose and on days 7 and 14 using the numerical Draize scoring. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 h after application and once daily for 14 days. All animals were observed twice daily for mortality. Body weight were recorded pretest, weekly and at termination. Finally, rabbits were examined for gross pathology.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the dermal application

Clinical signs:

other: Instances of few feces were observed in one animal. There were no other abnormal signs noted during the observation period. Neither erythema nor oedema was detected.

Gross pathology:

Necropsy results were normal.

Interpretation of results:

other: CLP criteria not met

Conclusions:

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

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance, 'di-C18-22 AAEMIM-MS' (active: 100%), according to OECD Guideline 402, in compliance with GLP. Five male and five female New Zealand White rabbits were exposed to 2000 mg/kg bw test substance (3.5 mL in water) under a semi-occlusive type of coverage on a clipped skin free of hair. The test substance was kept in contact with the skin for 24 hours. Dermal responses at test sites were recorded at 24 h postdose and on days 7 and 14 using the numerical Draize scoring. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours after application and once daily for 14 days. Mortality was checked twice daily. Body weight was recorded pre-test, weekly and at termination. Finally, rabbits were examined for gross pathology. All animals survived the dermal application. Instances of few faeces were observed in one animal. There were no other abnormal signs noted during the observation period. Neither erythema nor oedema was detected. Body weight changes and gross examination were normal. Under the study conditions, the rabbit dermal LD50 was determined to > 2000 mg/kg bw (MBRL, 2010).

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good quality Guideline compliant study.

Additional information

Oral:

A study was conducted to determine the acute oral toxicity of the read across substance, 'di-C16-18 and C18-unsatd. AAEMIM-MS', according to OECD Guideline 423 (Acute Toxic Class Method), in compliance with GLP. Three FemaleHanRcc: WIST(SPF)rats were administered the test substance by oral gavage at a dose of 2000 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. There was no mortality in this study. No evidence of systemic toxicity was noted during the study period. No toxicologically significant effects on bodyweight were recorded during the study period and no abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw (Arcelin, 2010). Based on the results of the read across study, similar oral LD50 value can be expected for the test substance, 'di-C18-22 AAEMIM-MS'.

 

Dermal:

A study was conducted to determine the acute dermal toxicity of the test substance, 'di-C18-22 AAEMIM-MS' (active: 100%), according to OECD Guideline 402, in compliance with GLP. Five male and five female New Zealand White rabbits were exposed to 2000 mg/kg bw test substance (3.5 mL in water) under a semi-occlusive type of coverage on a clipped skin free of hair. The test substance was kept in contact with the skin for 24 hours. Dermal responses at test sites were recorded at 24 h postdose and on days 7 and 14 using the numerical Draize scoring. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours after application and once daily for 14 days. Mortality was checked twice daily. Body weight was recorded pre-test, weekly and at termination. Finally, rabbits were examined for gross pathology. All animals survived the dermal application. Instances of few faeces were observed in one animal. There were no other abnormal signs noted during the observation period. Neither erythema nor oedema was detected. Body weight changes and gross examination were normal. Under the study conditions, the rabbit dermal LD50 was determined to > 2000 mg/kg bw (MBRL, 2010).

 

Inhalation:

The substance is a solid with a low vapour pressure at room temperature. Due to its physical state and physical chemical properties it is unlikely that this substance will form inhalable dust, mist or fumes during normal processing and use conditions. In case inhalable forms of the substance are created under particular conditions (e. g. spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented 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 available study results, the test substance, 'di-C18-22 AAEMIM-MS', does not warrant an acute toxicity classification, according to the EU CLP criteria (Regulation 1272/2008/EC).