Reaction product of: stearyl-diethanol-amine with C16-C18 saturated fatty acids

Endpoint summary

Description of key information

Acute oral toxicity study (limit test) according to OECD TG 423 was conducted with single gavage administration on 6 female rats.
Female LD50 oral: >2000 mg/kg bw. No adverse effects observed at the dose 2000 mg/kg bw
Acute dermal toxicity study(limit test) according to OECD TG 402 was conducted on 5 male and 5 female rats.
Male/female LD50 dermal: >2000 mg/kg bw. No adverse effects observed at the dose 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16-31 July 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD 423

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test Animals
Species Wistar rats
Source Velaz Prague, Czech Republic
Number and Sex of Animals 6 females
Age at First Dose
At least 8-12 weeks; female animals were non-pregnant and
nulliparous
Animal Health The health condition of animals was examined by a veterinarian before
initiation of the study.
Acclimatisation The animals were acclimated under the conditions identical to the
conditions during the experiment 5 days prior to the start of treatment.
The acclimation was according to the standard operation procedure.
Housing Condition The animals were housed in plastic cages suspended on stainless steel
racks, up to 3 animals per cage in a room equipped with central airconditioning.
The room temperature was maintained within the range
of 22 ± 2° C, relative humidity within 55 ± 10 %. The light regimen
was set to a 12-hour light /12-hour dark cycle. The sanitation was performed according to the standard operation procedures
Diet A laboratory food Altromin (Altromin Spezialfutter GmbH, Germany)
was offered in recommended doses each day approximately at the
same time. The certificate of analysis is included in the raw data.
Water The animals received tap water for human consumption. Supply of
drinking was unlimited. The quality of drinking water is periodical
analysed (including microbiological control) and recorded; certificate
of analysis is included in raw data.
Bedding Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification Each animal was marked with an ID number. Each cage was affixed
with a cage card containing pertinent animal and study information.
The animals in cages were marked by a line on the tail with an ink
marker.
Justification for the Choice
of Species
Normally females are used in the test according to OECD TG 423
because mostly females are the more sensitive gender.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals
were fasted prior to dosing (food but not water were withheld over-night). Following the period of
fasting, the animals were weighted and the test item administered. After the test item had been
administered, food was withheld for further 3-4 hours.

Doses:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg.
Available information indicates test item is likely to be nontoxic considering to acute toxicity. A
limit dose of 2000 mg/kg was used as starting dose. Group of 3 females were dosed. Test itemrelated
mortality was not observed during 24 hours group of 3 females were tested at the same dose.

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Clinical Observation
Animals were observed individually immediately after the administration of the test item and then
0.5, 1, 2, and 4 hours later. Then each animal was inspected for the next 14 days.
Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory,
circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour
pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea,
lethargy, sleep and coma
Individual weights of animals were determined shortly before the test item was administered and at
weekly thereafter. Weight differences after first and second weeks after application were calculated
and recorded.
All test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful
examination of external surface of the body, all orifices, and cranial, thoracic and abdominal
cavities and their contents. All gross pathological changes were recorded for each animal.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All 6/6 females survived the limit dose 2000 mg/kg.

Clinical signs:

other: No mortality was observed during the study. Animals lived through observation period without important visible signs of intoxication. Neither change of health nor negative reactions were registered.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopically changes were noticed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on OECD 423 Annex 2d: Test Procedure with a Starting Dose of 2000 mg/kg Body Weight it
can be concluded that the substance is classified in Category 5/Unclassified with
the cut off LD50 ≥ 5000 mg/kg, after single oral administration to Wistar rats.

Executive summary:

The test item administered to 6 females in limit dose 2000 mg/kg did not cause

death. All females survived the limit dose 2000 mg/kg. No body weight losses were observed

between one and two week after administration of the test item. No important signs of toxicity were

observed at the dosage of 2000 mg/kg during first 4 hours or in 14 day observation period. During

necropsy, no macroscopically changes were noticed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

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:

9-26 June 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD TG 402

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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:

Species: Wistar rats
Source: Velaz Prague, Czech Republic
Number and Sex of Animals Received/Used: 10 females and 5 males / 5 males and 5 females
Age at First Dose: 8-12 weeks; female animals were non-pregnant and nulliparous
Animal Health: The health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated to the condition identical to the conditions during the experiment 5 days prior to the start of treatment.
The acclimation was according to the standard operation procedure.
Housing Condition: The animals were housed in plastic cages suspended on stainless steel racks, up to 2-3 animals per cage, males and females separately in a room equipped with central air-conditioning. The room temperature was maintained within the range of 22 ± 2° C, relative humidity within
55 ± 10 %. The light regimen was set to a 12-hour light /12-hour dark cycle (deviation ± 30 minute). The sanitation was performed accordingto the standard operation procedures.
Diet: A laboratory food Altromin (Altromin Spezialfutter GmbH, Germany) was offered in recommended doses each day approximately at the same time after dosing. The certificate of analysis is included in the raw data. The food consumption was recorded.
Water: The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded; certificate of analysis is included in raw data.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line on the tail with an ink marker.
Justification for the Choice of Species: Normally females are used in the test according to OECD TG 402 because mostly females are the more sensitivegender, but there is still a possibility that this assumption will not be confirmed. For this reason, one dose in males was used to verify sensitivity of sexes after assessing acute toxicity in females.

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving. A precise amount of the test item was aspirated into an adjustable pipette and application directly on the shaved skin of back in a single dose uniformly on over an area approximately 10 % of the total body surface area. Test item was held in contact with the skin by using a Cosmopor E and a semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period. At the end of the exposure period, any residuals of the test item were removed by using lukewarm water without altering the existing response or integrity of the epidermis.

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Sighting Study
The purpose of the sighting study was to allow selection of the appropriate starting dose for the main test. The starting dose for sighting study could be selected from the fixed dose levels of 50, 200, 1000, and 2000 mg/kg. Available information indicated that the test item was likely to be nontoxic regard to acute toxicity. Therefore, a limit dose of 2000 mg/kg was used as starting dose. One female rat was dosed. Test item-related mortality was not produced during 24-hours exposure period. The sighting study was finished; the main test was started with dose of 2000 mg/kg.

Main Study
A total of five female rats (one from the sighting study with an additional four animals) were dosed with a dose of 2000 mg/kg. Test item-related mortality was not produced during 24 hours. An additional group of 5 male rats were tested at the same dose.

Clinical Observation
Animals were observed individually immediately after the application of the test item and then ½, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weight
Individual weights of animals were determined shortly before the test item was applicated and at weekly thereafter. Weight differences after first and second week after application were calculated and recorded.

Necropsy
All test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents. All gross pathological changes were recorded for each animal.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

All 5/5 females and 5/5 males at the limit dose of 2000 mg/kg survived. No further dosing was necessary.

Clinical signs:

other: No mortality was observed during the study. No important symptoms were observed during the first 4 hours neither in females nor in males or in 14 days observation period.

Gross pathology:

All animals (5 females and 5 males) were necropsied. During necropsy, no macroscopical changes were noticed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on OECD TG 402 and OECD Draft TG 434 it can be concluded that for the substance LD50 is equal to 2000 mg/kg, after single dermal application to Wistar rats.

Executive summary:

The test item applicated to 5♀ and 5♂ in limit dose 2000 mg/kg did not cause

death. All 5/5 females and 5/5 males survived the limit dose 2000 mg/kg thereafter no further

dosing was necessary.

No body weight losses were observed one and two week after application of the test item. No

important symptoms were observed during first 4 hours neither in females nor in males or in 14

days observation period. During necropsy, no macroscopically changes were noticed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

During both studies on oral and dermal acute toxicity, the substance did not evidence any adverse effects at the limit dose of 2000 mg/kg. According to these results, the substance is not classified for acute oral and dermal toxicity.

For acute inhalation toxicity no data is available.