Dimethylammonium chloride

Endpoint summary

Description of key information

Skin: Fluhr (2005): 1 % DMA in distilled water on human skin (paravertebral mid back). No significant irritation, but barrier disruption of the stratum corneum.
Skin and eyes: BASF, Gewebetoxikologische Grundprüfung, 1980, 40 % DMA in aqueous solution, in that concentration irritation of the skin and the eye.
Respiratory tract: DMA is an essentially irritant for the upper airways of rodents. (Gagnaire, 1989)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin corrosion

A BASF AG internal procedure for skin irritation was used as in following described: two animals were treated with a 40 % DMA solution for 3 min and 4 animals for 4 hours using occlusive conditions. An application site of 2x2 cm was covered with the liquid test substance. After the application the skin was washed with Lutrol (50%). The animals were observed for 8 days and skin changes were recorded daily. On days 1 to 8 the exposure sites were examined and scored for erythema and edema on a graded scale of 0 to 2 or 4 respectively. The test substance dimethylamine aqueous solution was irritating to the skin of rabbits. The report describes findings after 24 hours and at the end of the observation period (8 days). The 3 min exposure caused in every animal severe erythema and slight edema. The 4 h exposure caused severe erythema and severe edema.

Skin irritation

In the study performed by Fluhr et al, 2005, it was shown that biogenic amines (1 %) cause disruption of the permeability barrier. The biogenic amines without the combination with sodium lauryl sulphate = SLS (acetic acid = AA/ AA, DMA/DMA, TMA/TMA) did not induce a significant irritation measured via chromometry. The values assessed with the visual score were overall very low. However, the application of each of the three biogenic amines did not reveal a significant irritation or increase in SC pH. Sequential application of SLS further enhanced the barrier disruption induced by the biogenic amines. The only exception was the irritation parameter measured via chromometry, where no significant increase of redness could be observed. The TMA/SLS irritation and barrier disruption was slightly more prominent than those induced by ammonium hydroxide = AM/SLS and DMA/SLS, which can be explained by the higher concentration (1.5 vs. 1.0%). Since these results are detectable in all analyzed parameters, they assume that the described features may be consistent properties of biogenic amines. This dichotomy of usually related parameters of barrier disruption and induction of irritation might be based on the fact that the amines disturbed the intercellular barrier-lipid processing but did not induce a pH change and a subsequent increase in pH.

They assume that the mechanism by which the biogenic amines induce a barrier disruption and inflammatory reaction are different from that of SLS. The contact with both classes of irritants however did not show over additive effects. So the skin represents a better barrier for DMA induced alterations than all the mucosal membrane investigated.

Eye corrosion

For eye irritation a Draize test was performed on 3 rabbits (Vienna White) by BASF (1980). One single application was done with 100 µl, the eyes were not washed out afterwards. The untreated eye served as control. The test duration was 14 days. Scoring of ocular lesions was done according to the method of Draize et al. (1944). The application of the test substance caused an irreversible cornea and conjunctivae disturbance of a score of 4 of 4 and the animals did not recover within 8 days after treatment.

According to the authors, the test substance was classified as irritating to the rabbit eyes when applied without rinsing.

Respiratory irritation

No data available

Conclusions:

Since no information for dimethylamine hydrochloride is available, reading across from dimethylamine was performed. This is difficult since dimethylamine is highly alkaline and therefore possesses corrosive and irritating potential. Dimethylamine was irritating to the skin of rabbits (BASF, 1980). Every animal showed severe erythema and slight to severe edema of the skin. Dimethylamine was also highly irritating to the eyes of rabbits (BASF, 1980) and the animals did not recover within 8 days after treatment. Fluhr et al, 2005, showed that biogenic amines (among which dimethylamine was tested) cause disruption of the permeability barrier. The biogenic amines without the combination with sodium lauryl sulphate = SLS (acetic acid = AA/ AA, DMA/DMA, TMA/TMA) did not induce a significant irritation measured by chromometry. The values assessed with the visual score were overall very low. So the skin represents a better barrier for DMA induced alterations than all the mucosal membrane investigated.

This is not the case with dimethylamine hydrochloride. Since DMA-HCl has a pH between 5 and 6 it is clear that the strong corrosive effects that are caused by dimethylamine are not to be expected with the salt. Still dimethylammonium chloride is classified as irritating to the skin an to eyes.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Since skin and eye irritation studies were performed with dimethylamine (native substance), classification for dimethylamine hydrochloride cannot be based on the available study results. DMA is classified as following:

according to DSD as:

- (aqueous): C, R34, Corrosive, causes burns;

- (gaseous): Xi, R41 Irritant, Risk of serious damage to eyes; Xi, R 37/38 Irritant, Irritating to respiratory system and skin.

according to GSH:

- (aqueous): Skin Corr. 1B. H314: Causes severe skin burns and eye damage; STOT Single Exp. 3, H335: May cause respiratory irritation;

- (gaseous): Skin Irrit. 2 H315: Causes skin irritation.

The substance Dimethylamine hydrochloride (CAS-No. 506-59-2, EC-No. 208-046-5) is a near analogue to Dimethylamine (CAS-No. 124-40-3, EC-No. 204-697-4). Merely from comparing the molecular structures of these two secondary amines it is apparent that Dimethylamine hydrochloride (Dimethylammonium hydrochloride; DMA-HCl) and Dimethylamine (DMA) are closely related to each other. DMA-HCl is the chloride of DMAormorespecifically, the gas DMA reacts with hydrochloric acid to form the salt DMA-HCl, an odourless white solid. At this DMA`s unshared electron pair on nitrogen forms a coordinate bond with the proton hydrogen, accompanied bychlorinebonding ionically. If alkali (e.g. sodium hydroxide) is added to solutions of DMA-HCl the free amine DMA will be liberated. Hence, under specific conditions the toxicological and ecotoxicological properties of the gaseous substance DMA and its salt DMA-HCl (even in aqueous solution) are equal and as a result, read across is justified.

Dimethylamine hydrochloride does not possess strong alkaline properties due to ionic bonding in salt (the unshared electron pair of nitrogen is implicated in the coordinate bond).Therefore, its irritating properties are in a range of less severity than native DMA.

Classification is warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

according to DSD as: Xi, R 36/38 Irritant, Irritating to eyes and skin;

according to GHS as: Skin Irrit.2, H315: Causes skin irritation, Eye Irrit.2, H319: Causes eye irritation.