N-[3-(dimethylamino)propyl]docosanamide

Endpoint summary

Description of key information

Data on acute toxicity is not available for the target substance DIMAPDO. For the assessment of acute effects of DIMAPDO the results from the following study is taken into consideration: 
Acute oral toxicity: LD50 expected to be > 2000 mg/kg bw based on a read-across study with the source substance N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl] docosanamide (C22) 50:50 (w/w %) according to OECD Guideline 423, GLP compliant

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

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: tertiary amines, amides, and fatty acid chains with comparable length and degree of saturation (corresponding to scenario 2 of the read-across assessment framework)

The read-across hypothesis is based on structural similarity of target and source substances. The target and source chemicals have a very similar structure in that they are comprised of a hydrophobic (alkyl) and hydrophilic (amine headgroup) end. Due to this motif they form micelles (colloidal dispersions) and have surfactant properties.
Based on available experimental data, including key physicochemical properties and data from genotoxicity studies, the read-across strategy is supported by a similar toxicological profile of all substances.

Therefore, read-across from the existing toxicity studies conducted with the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A justification for read-across is attached to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See justification for read-across attached to IUCLID section 13.

3. ANALOGUE APPROACH JUSTIFICATION
See justification for read-across attached to IUCLID section 13.

4. DATA MATRIX
See justification for read-across attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Route of administration:

oral: gavage

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: no mortalities

Interpretation of results:

GHS criteria not met

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

No experimental data on acute toxicity are available for the target substance DIMAPDO. However, reliable data on acute oral toxicity are available for the source substance N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl] docosanamide (C22) 50:50 (w/w %). A justification for read-across is attached to IUCLID section 13.

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 11 weeks old Wistar strain rats were given a single oral dose of the source substance N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl] docosanamide (C22) 50:50 (w/w %) in sesame oil by gavage at a dose of 2000 mg/kg bw and observed for 14 days.

All animals survived until the end of the study period. One hour after dosing, a slightly ruffled fur was noted in three out of six treated females and persisted up to the 5-hour observation. Otherwise, no clinical signs were observed in any animal at any observation timepoint. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. Oral LD50 (rat, females) > 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 DIMAPDO. 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. DIMAPDO 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 7.1E-009 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 of two source substances with high similarity to DIMAPDO after oral exposure. Therefore the acute intrinsic toxic activity of DIMAPDO 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

A study on acute dermal toxicity does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (skin irritation, skin sensitisation).

Based on the available information, the acute toxicity potential of DIMAPDO is low. There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

 

 

 

 

 

 

 

 

 

Justification for classification or non-classification

Based on the available relevant and reliable data, DIMAPDO does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to acute toxicity.