N-[3-(dimethylamino)propyl]stearamide

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw, OECD Guideline 423, GLP compliant

Acute dermal toxicity: LD50 expected to be > 2000 mg/kg bw based on read-across

Acute inhalation toxicity: not necessary due to exposure considerations

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:

2012-05-31 to 2012-06-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

GLP compliance:

yes

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
- Age at study initiation: 8-9 weeks
- Fasting period before study: overnight prior to dosing and until approximately 1 hour after the second administration of the test substance
- Housing: 3/cage
- Diet (e.g. ad libitum): pelleted rodent diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24°C
- Humidity (%): 40-70%
- Air changes (per hr): app. 15/h
- Photoperiod (hrs dark / hrs light):12/12

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10% w/w
- Amount of vehicle (if gavage): 10 mL/kg bw

DOSAGE PREPARATION (if unusual):
2000 mg/kg bw were achieved by administration of two times 1000 mg/kg bw, since a 20% w/w formulation was not homogenous based on trial formulations.

Doses:

2000 mg/kg bw, given as 2 dosages of 1000 mg/kg bw within 24 hours. The first on t=0 and the second on t=3 hours. Multiple dosages given within 24 hours are regarded as a single dose

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: mortality: twice daily; clinical signs: 0, 2, 4 h, daily thereafter
- Frequency of weighing:
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

2/6 animals died on day 2 and 3, respectively

Clinical signs:

other: Clinical signs shown by the animals found dead and surviving animals included lethargy, hunched posture, uncoordinated movements, piloerection, diarrhoea, chromodacryorrhoea, pallor, and/or ptosis. The surviving animals had recovered from the symptoms bet

Gross pathology:

One female found dead showed watery-turbid fluid in the stomach and watery-clear, yellowish fluid in the small intestines. The other female found dead showed a reduced size of the spleen. Pelvic dilation of the kidneys was noted in one surviving female. Other surviving females had no macroscopic abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Stearic acid 3-(dimethylaminopropyl)amide in female rats was > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 423, adopted 17 December 2001 and EU method B.1 tris, May 2008, 6 female, fasted, 8-9 weeks old Wistar strain ratswere given a single oral dose of Stearic acid 3-(dimethylaminopropyl)amide in Propylene glycol by gavage at a dose of 2000 mg/kg bw and observed for 14 days.

The test substance was administered as 2 dosages of 1000 mg/kg bw within 24 hours. The first on t=0 and the second on t=3 hours. Multiple dosages given within 24 hours are regarded as a single dose.

2/6 animals died on day 2 and 3, respectively. Clinical signs shown by the animals found dead and surviving animals included lethargy, hunched posture, uncoordinated movements, piloerection, diarrhoea, chromodacryorrhoea, pallor, and/or ptosis.

The surviving animals had recovered from the symptoms between days 7 and 10.

The two animals found dead showed either slight weight gain or weight loss. 3/4 surviving females showed body weight loss between days 1 and 8. These animals again gained body weight between days 8 and 15. One surviving female showed body weight gain that was considered to be similar to that expected of normal untreated animals of the same age and strain.

One female found dead showed watery-turbid fluid in the stomach and watery-clear, yellowish fluid in the small intestines. The other female found dead showed a reduced size of the spleen. Pelvic dilation of the kidneys was noted in one surviving female. Other surviving females had no macroscopic abnormalities.

 

Oral LD50 (rat, females) > 2000  mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

OECD & EC guideline study, no deviations, GLP

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

In an acute oral toxicity study according to OECD guideline 423, adopted 17 December 2001 and EU method B.1 tris, May 2008, 6 female, fasted, 8-9 weeks old Wistar strain rats were given a single oral dose of Stearic acid 3-(dimethylaminopropyl)amide in Propylene glycol by gavage at a dose of 2000 mg/kg bw and observed for 14 days.

The test substance was administered as 2 dosages of 1000 mg/kg bw within 24 hours. The first on t=0 and the second on t=3 hours. Multiple dosages given within 24 hours are regarded as a single dose.

2/6 animals died on day 2 and 3, respectively. Clinical signs shown by the animals found dead and surviving animals included lethargy, hunched posture, uncoordinated movements, piloerection, diarrhoea, chromodacryorrhoea, pallor, and/or ptosis.

The surviving animals had recovered from the symptoms between days 7 and 10.

The two animals found dead showed either slight weight gain or weight loss. 3/4 surviving females showed body weight loss between days 1 and 8. These animals again gained body weight between days 8 and 15. One surviving female showed body weight gain that was considered to be similar to that expected of normal untreated animals of the same age and strain.

One female found dead showed watery-turbid fluid in the stomach and watery-clear, yellowish fluid in the small intestines. The other female found dead showed a reduced size of the spleen. Pelvic dilation of the kidneys was noted in one surviving female. Other surviving females had no macroscopic abnormalities. Oral LD50 (rat, females) > 2000 mg/kg bw

A further acute oral toxicity study is available: 5 fasted Sprague-Dawley rats/sex/group were given a single oral dose of Stearic acid 3-(dimethylaminopropyl)amide by gavage as 40% w/w suspension in deionized water at dose levels of 1420, 1990, 3910 and 5470 mg/kg bw (dose volume 1.67, 2.21, 4.44 and 6.22 mL/kg bw). The dose levels were selected based on the results of a range finding study. Animals were observed daily up to 14 days.

The following mortalities were reported:

0/5 male and 0/5 female rats died at 1420 mg/kg bw dose level

0/5 male and 0/5 female rats died at 1990 mg/kg bw dose level

2/5 male and 4/5 female rats died at 3910 mg/kg bw dose level

5/5 male and 5/5 female rats died at 5470 mg/kg bw dose level 

All mortalities occurred within 8 days of test substance administration.

Clinical signs observed during the study period included diarrhea, soft stool, brown stained abdomen, anal or urogenital region, hypoactivity, hypersensitivity to touch, red stained nose and mouth, hair loss on abdomen and hindquarters, ataxia, emaciation, bloated abdomen, red stain around eyes, piloerection, lacrimation, high carriage, dyspnea, hypothermia to touch and death.

During necropsy, the most frequently recorded observations were in those animals which died during the course of test. The mucosa was reddened in four animals (3 animals from 3910 mg/kg bw and 1 animal from 5470 mg/kg bw dose group) which was probably treatment related. All other observations were considered related to postmortem changes and and/or incidental findings which were not treatment related. All observations recorded on the sacrificed animals were also considered to be incidental. Based on results, the acute oral toxicity (LD50) of Stearic acid 3-(dimethylaminopropyl)amide was determined to be 3490 mg/kg bw/d as 40% suspension, corresponding to 1396 mg a.i./kg bw.

 

However, this second study is less reliable. No constant dose volume has been applied (1.67, 2.21, 4.44 and 6.22 mL/kg bw). Although the maximum applied dose volume is in the range of recommendations (up to 10 mL/kg bw), a constant volume over the range of doses should have been applied to minimize the varying parameters and allow for equal treatment across all dose groups. Moreover, stability of the test substance after the preparation procedure (including heating) was not demonstrated.

As a newer and completely valid OECD guideline study (reliable without restrictions) is available, that study is considered to be the key study for this endpoint and to determine the acute toxicity. Thus, the oral LD50 of Stearic acid 3-(dimethylaminopropyl)amide is > 2000 mg/kg bw.

 

Acute inhalation toxicity

Given that inhalation is not a relevant route of exposure, testing by the inhalation route is not necessary according to REACH Regulation Annex VIII 8.5.2 Column 2. Inhalation is not a relevant route of exposure to Stearic acid 3-(dimethylaminopropyl)amide. This applies to both workers and the general population and is due to the physicochemical properties of the substance and the nature of the products where it is used. Stearic acid 3-(dimethylaminopropyl)amide is a waxy solid paste. Generation of inhalable particles such as dust or aerosols is therefore not to be expected. Vaporisation needs not to be considered due to the substance’s very low vapour pressure of < 3.4E-08 Pa. The generation of aerosols is excluded by technical means or product design. The substance is not used in spray applications. The most likely route of human exposure for workers and consumers is the dermal route. Results of laboratory animal studies show a low acute toxicity after oral exposure. Therefore the acute intrinsic toxic activity of Stearic acid 3-(dimethylaminopropyl)amide is considered to be low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely and therefore the conduct of an acute inhalation toxicity study is unjustified.

 

Acute dermal toxicity

The testing of acute dermal toxicity of Stearic acid 3-(dimethylaminopropyl)amide is scientifically not justified. According to the COMMISSION REGULATION (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity, recent “scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.” The oral LD50 was determined to be > 2000 mg/kg bw based on read-across from a closely related substance. Thus, no toxicity via the dermal route is to be expected.  

Justification for classification or non-classification

The oral LD50 of Stearic acid 3-(dimethylaminopropyl)amide was assessed to be > 2000 mg/kg bw. Acute toxicity via the dermal route or via inhalation is not expected.

According to GHS Regulation EC No 1272/2008 no classification and labelling for acute toxicity is necessary.