C12-16-(even numbered)-alkyl-dimethylammonium lactate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: VCI inhalation DNEL for corrosive substances

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

The toxicity profile of the substance is evaluated using analogue approaches and (Q)SARs. Based on the available information, the substance is classified as Cat.4 for acute oral toxicity and Cat. 1B for skin irritation/corrosion,according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). No genotoxic potential is derived for the substance and therefore classification for genetic toxicity is not warranted. Accordingly, the conclusion of low hazard is derived for systemic effects following dermal acute/short term exposure, and high hazard for local effects following dermal exposure (acute/short term and longterm exposure). Although no data is available for eye irritation, high hazard is derived for local effects of the eyes based on the corrosive property of the substance.

Worker DNEL: Long-term/short term for inhalation route, local effects

The German VCI ("Verband der chemischen Industrie") established an inhalation DNEL for local effects for corrosive substances of 1 mg/m³that should be applied for long- and short-term exposure equally. The derivation of this value is fully described in Messinger (2014). Briefly, the DNEL is a generic cut-off value based on an extensive analysis of the German occupational exposure limit (OEL) values as published in TRGS 900 (“Technnische Regeln für Gefahrstoffe”) for substances that are legally classified as corrosive. Substances identified as corrosive in self-classifications only were not considered, since they lack a peer review of the classification assigned. After exclusion of some (groups of) substances, such as CMR substances, the evaluation retrieved 40 corrosive substances with OEL values effective in Germany. In addition to the dermal effects, corrosive substances often display pronounced acute toxicity when administered by other pathways, especially via inhalation. When all very toxic (R26 or R27 or R28) and all sensitising (R42 or R43) substances were removed from the set of 40 corrosive substances, only 2/24 (8%) substances had an OEL below 1 mg/m³. The two substances are 1) sulfuric acid, a very strong acid vigorously reacting with water and b) barium hydroxide, for which the low OEL was derived on the basis of systemic effects (Messinger, 2014).

Overall, the applicability domain of the DNEL of 1 mg/m³for corrosive substances is defined as follows (Messinger, 2014):

- The substance is not a CMR substance, a heavy metal derivative, a sensitiser and does not hydrolyse to strong acids/bases

- The substance is not very toxic by ingestion, dermal contact or inhalation.

The submission substance fulfils these criteria and the DNEL of 1 mg/m³can be applied.

With this DNEL for local effects, any potential systemic effects are covered as well.

Reference 

Messinger, H.: An approach for the delineation of a generic cut-off value for local respiratory tract irritation by irritating or corrosive substances as a pragmatic tool to full fill REACH requirements. Regul. Toxicol. Pharmacol. 2014.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - General Population

The toxicity profile of the substance is evaluated using analogue approaches and (Q)SARs. Based on the available information, the substance is classified as Cat.4 for acute oral toxicity and Cat. 1B for skin irritation/corrosion,according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). No genotoxic potential is derived for the substance and therefore classification for genetic toxicity is not warranted. Accordingly, the conclusion of low hazard is derived for systemic effectsfollowingacute/short term exposure, and high hazard for local effects following dermal exposure (acute/short term and longterm exposure). Although no data is available for eye irritation, high hazard is derived for local effects of the eyes based on the corrosive property of the substance. Since no data on dose-response relationship is available, no DNEL could be derived.

The analogue approach using dimethyl alkylamines (DMAs) with comparable length of alkyl chain as source chemicals is justified:

The target chemical Amines, C12-16-alkyldimethyl, lactates is an ionic compound that results from the neutralization reaction of the compounds of lactic acid and C12-16-DMA. In aqueous solution or in a biological fluid, it could be dissociate as lactic acid and C12-16-DMA. Therefore, the toxicity toxicological profile of the target chemical should be comparable to that of C12-16-DMA and lactic acid. Lactic acid is a natural, functional metabolite in mammals, and serves as mammalian fuel. From previous investigations, it is concluded that lactic acid does not present a hazard for the human health based on its low hazard profile. Based on the basic concept of “chain length category”, the use of toxicity data of other dimethyl alkylamines with comparable length of alkyl chain for read-across purpose to C12-16-DMA and the target chemical is justified. The dissociated product of the target chemical – C12-16-DMA and the source chemicals of C12-DMA, C14-DMA, C16-DMA, C18-DMA, C12-14-DMA, C12-16-DMA, C12-18-DMA and C16-18-DMA belong to the homologues series of fatty amines and form a “chain length category”, where there is an incremental increase in the number of CH2 units. Therefore, it can be reasonably assumed that C12-16-DMA and other dimethyl alkylamines (C12-DMA, C14-DMA, C16-DMA, C18-DMA, C12-14-DMA, C12-16-DMA, C12-18-DMA and C16-18-DMA) share the same toxic mode of action.

The major available physic-chemical properties of target and source chemicals are in a comparable range and support hypothesis that the source and the target chemicals behave similarly or as a function of carbon chain length.

All the chemicals are assessed using the rule based expert system DEREK Nexus based on their chemical structures. The assessment results are identical for the target chemical and source chemicals: all the chemicals are predicted as negative for mutagenicity in bacteria. No toxicity potential or structure alert is identified.

With regard to the endpoint of skin irritation/corrosion, corrosive effect was identified for the source chemicals of C12-DMA, C16-DMA, C12-14-DMA, C12-18-DMA and C16-18-DMA. The target chemical is considered as corrosive to skin (Cat 1B) based on the analogue approach. For this endpoint, the analogue approach is also justified considering the “worst case” scenario.

Based on these similarities in structural, functional and metabolic behavior of DMAs and DMA lactates, it is therefore reasonable and scientifically justified to use analogue DMAs as source molecules to inform endpoint related data gaps for the target molecule under discussion.