Amides, C12-18, N-[3-(dimethylamino)propyl]

Endpoint summary

Description of key information

One key acute oral toxicity study is available.  The study was conducted according to OECD Guideline 423 and used female Sprague-Dawley rats as the test species. The study concludes to GHS classification Category 3 for acute oral toxicity (LD50 between 50 and 300 mg/kg bw) with a LD50 cut-off of 300 mg/kg bw for cocoamidopropyldimethylamine. No studies are available for acute inhalation or dermal toxicity.

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:

10 September 2009 to 22 October 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France. Strain Rj: SD (IOPS Han)
- Age at study initiation: 8 or 9 weeks old
- Weight at study initiation: mean 207 ± 14 g
- Fasting period before study: Overnight and up to 4 h after dosing
- Housing: The animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and one to three rats of the same group during the treatment period. Each cage contained autoclaved sawdust
- Diet (e.g. ad libitum): All the animals had free access to SSNIFF R/M-H pelleted maintenance diet ad libitum, except during the fasting period.
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: From: 10 September 2009 To: 22 October 2009

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Based on the results of the solubility assay.
- Lot/batch no. (if required): 128K0040 and 049K0043
- Purity: Not documented

MAXIMUM DOSE VOLUME APPLIED:
10mL/kg

PREPARATION OF DOSING SOLUTION:
The test item was administered as a solution in the vehicle. The test item was prepared at the chosen concentrations in the vehicle under magnetic stirring for at least 10 minutes. The test item preparation was made freshly on the morning of administration by the CIT Pharmacy and any unused material was discarded that same day.

The dosage form preparations were administered to the animals using a dose volume of 10 mL/kg.
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 2 mL plastic syringe (0.1 mL graduations).
The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

Doses:

2000, 300 and 50 mg/kg

No. of animals per sex per dose:

Groups of 3 females were used at each dose level. For the 300 and 50 mg/kg levels two groups were dosed in each case

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item (day 1), then at least once a day until the end of observation period (day 15). The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: No information

Statistics:

No information provided.

Preliminary study:

Not relevant

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Mortality:

At the dose level of 2000 mg/kg, all females were found dead on day 2.
At the dose level of 300 mg/kg, one of the three first treated animals and two of the second treated females were found dead on days 2 and 3.
No mortalities were observed in the 50 mg/kg dose group.

Clinical signs:

other: At the dose level of 2000 mg/kg, hypoactivity or sedation, piloerection, dyspnea (all animals) and soft faeces (one animal) were observed prior to their deaths. In the 300 mg/kg dose group, hypoactivity or sedation, piloerection, dyspnea, hypersalivation

Gross pathology:

In one female in the 2000 mg/kg dose group, soft faeces were observed in the intestines. Macroscopic examination of the main organs of the other animals revealed no apparent abnormalities.

Other findings:

No other observations were noted.

No additional information provided.

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the dose-level of 300 mg/kg of the test item, Coco amidopropyldimethylamine, could be established as the oral LD50 in rats.

Executive summary:

In a acute oral toxicity study by Acute Toxic Class Method (OECD 423), the test substance, Coco amidopropyldimethylamine was administered in corn oil via oral gavage to female Sprague Dawley rats at dose ranges of 50, 300 and 2000mg/kg. The test substance was administered in a dosage volume of 10mL/kg. One group of 3 females was tested at 2000 mg/kg while at 300 and 50 mg/kg, 2 groups of 3 females each were tested. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the dose-level of 2000 mg/kg (three females), all females were found dead on day 2. Hypoactivity or sedation, piloerection, dyspnea and/or soft faeces were observed prior to their deaths. At necropsy, no apparent abnormalities were observed in any animal. At the dose-level of 300 mg/kg (six females), three females were found dead on day 2 or 3. Hypoactivity or sedation, piloerection, dyspnea, hypersalivation, loud breathing and/or tonico-clonic convulsions were noted prior to their deaths. Hypoactivity, piloerection, dyspnea and hypersalivation were observed in three out of six surviving females on day 1. Loud breathing was noted in two out of three surviving females on day 2 then from day 8 until the end of the observation period (day 15) as well as dyspnea and abdominal swelling in one surviving female on days 13 and 15, respectively. A body weight loss was noted in one surviving animal between day 8 and day 15 (-19%). Additionally, when compared to CIT historical control data, a lower body weight gain was noted in one surviving female between day 1 and day 8 (returning to normal thereafter). At necropsy, no apparent abnormalities were observed in any animal. At the dose-level of 50 mg/kg (six females), no mortality or clinical signs were noted during the observation period. When compared to CIT historical control data, a lower body weight gain was noted in two out of six females between day 1 and day 8 (returning to normal thereafter). At necropsy, no apparent abnormalities were observed in any animal.

Under the experimental conditions of this study, the dose-level of 300 mg/kg of the test item, Coco amidopropyldimethylamine, could be established as the oral LD₅₀ in rats.

According to Regulation EC No. 2172/2008, the test substance should be classified as a Category 3 toxicant and should have the signal word Danger and the Hazard Statement H301: Toxic if swallowed. According to Directive 67/548/EEC, the test susbtance should be classified as Harmful and have the symbol Xn and the risk phrase R22: Harmful if swallowed associated with it.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The study is Klimisch 1 and GLP compliant

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral Toxicity:

In an acute oral toxicity study by Acute Toxic Class Method (OECD 423) , cocoamidopropyldimethylamine was administered in corn oil via oral gavage to female Sprague Dawley rats at dose levels of 50, 300 or 2000 mg/kg. The test substance was administered in a dosage volume of 10 mL/kg. One group of 3 females was tested at 2000 mg/kg while at 300 and 50 mg/kg, 2 groups of 3 females each were tested. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

In the 2000 mg/kg group (three females), all rats were found dead on day 2. Hypoactivity or sedation, piloerection, dyspnea and/or soft faeces were observed prior to their deaths. At necropsy, no apparent abnormalities were observed in any animal.

In the 300 mg/kg group (six females), three females were found dead on day 2 or 3. Hypoactivity or sedation, piloerection, dyspnea, hypersalivation, loud breathing and/or tonic-clonic convulsions were noted prior to their deaths. Hypoactivity, piloerection, dyspnea and hypersalivation were observed in three out of six surviving females on day 1. Loud breathing was noted in two out of three surviving females on day 2 then from day 8 until the end of the observation period (day 15) as well as dyspnea and abdominal swelling in one surviving female on days 13 and 15, respectively. A body weight loss was noted in one surviving animal between day 8 and day 15 (-19%). Additionally, when compared to historical control data, a lower body weight gain was noted in one surviving female between day 1 and day 8 (returning to normal thereafter). At necropsy, no apparent abnormalities were observed in any animal.

In the 50 mg/kg group (six females), no mortality or clinical signs were noted during the observation period. When compared to CIT historical control data, a lower body weight gain was noted in two out of six females between day 1 and day 8 (returning to normal thereafter). At necropsy, no apparent abnormalities were observed in any animal.

Under the experimental conditions of this study, the LD50 cut-off level was 300 mg/kg.

 

Acute inhalation toxicity:

There is no study available for acute inhalation toxicity for cocoamidopropyldimethylamine. REACH guidance R.7.a, chapter. 7.4 Acute toxicity, indicates that in principle no inhalation studies are needed when vapour pressure < 0.1 Pa at 20°C or particle size > 100 µm. Cocoamidopropyldimethylamine is a solid paste with a melting point of 23°C that is marketed or used in a non-solid or non-granular form and with a vp around 3.96 10-5 Pa at 25°C (EPI suite estimation). Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur.

 

Acute dermal toxicity:

No acute dermal study is available. The substance is classified as corrosive to skin and testing for acute toxicity is therefore not needed according to REACH regulation (EC) 1907/2006 (Annex VIII, point 8.5, column 2). Use and handling of the pure substance is only industrial and professional (formulation), and the classification of the substance as corrosive requires risk management methods which eliminate the risk of acute systemic toxicity by dermal route.

Justification for classification or non-classification

Available study result to GHS classification Category 3 for acute oral toxicity (LD50 between 50 and 300 mg/kg bw) based on LD50 cut-off of 300 mg/kg bw. Testing for dermal toxicity is not required in view of its corrosive properties.

There is no data on toxicity following exposures via inhalation. Related to low vp and no inhalable particles, no inhalation studies are required in view of limited exposure via inhalation.

 

No classification STOT-SE Cat.3 needed:

The active substance is not structurally related to any known class of neurotoxic chemicals. In addition, repeated dose studies did not show indications of specific neurotoxicity, in specific neurotoxicity measures as sensory activity, grip strength, and motor activity assessment.

 

Also available studies indicate that there is no need of a classification for aspiration hazard.