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Description of key information

No data are available on the skin and eye irritating properties of sodium diethyldithiocarbamate (SDEC) in its manufactured form (as ca. 26% aqueous solution). However an in vitro percutaneous absorption study with SDEC (TNO study 8918) is available that showed damaging effects of SDEC to the isolated human skin in vitro. Furthermore, reliable GLP-compliant guideline skin and eye irritation studies are available for its structural analogue sodium dimethyldithiocarbamate (SDMC), which differs from SDEC only by the chain length of alkyl substients at the amine function of dithiocarbamate moiety (methyl vs. ethyl). SDMC in its manufactured form (as 41% aqueous solution) was found not to be irritating to rabbit skin and eyes. Based on these studies and using a precautionary principle, it is considered acceptable to conclude that SDEC is irritating for skin and eye. Considering very low acute oral toxicity of SDEC (LD50 > 5000 in 19.4% aqueous solution), it does not appear likely that the substance in its manufactured and marketed form (as 26% solution) can be corrosive.

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

No skin and eye irritation studies with sodium diethyldithiocarbamate (SDEC) are available for assessment. However, anin vitropercutaneous absorption study with SDEC in its manufactured and marketed form (as ca. 26% aqueous solution) is available (TNO Quality of Life, 2010) that showed damaging effects of SDEC to the isolated human skin in vitro (see Section on toxicokinetics). Furthermore, two GLP-compliant guideline skin and eye irritation studies with rabbits are available with a structural analogue of SDEC, sodium dimethyldithiocarbamate (SDMC), also tested in its manufactured and marketed form (as 41.44% aqueous solution). SDMC is a structural homologue of SDEC, differing only in the carbon chain lengh of the alkyl substituents at the amine function of dithiocarbamate moiety (methyl vs. ethyl). SDMC is manufactured and marketed in aqueous solution with average concentration of 41%.

In the percutaneous absorption study with SDEC, isolated human skin was exposed during 24 hours to the undiluted (as manufactured) SDEC solution (23.4% SDEC solution) and as 10% dilution (2.34% SDEC solution) to study skin penetration. The 100% solution and the 10% solution interfered with the barrier function of the skin which can be concluded from the data were the relative absorption (percentage of the amount of substance exposed to the skin) for the 100% solution is higher than the relative absorption for the 10% solution. Furthermore, tape stripping was extremely difficult as a result from the damaging effect of the test solutions on the stratum corneum, which was already observed during washing after 8 hours of exposure.

Because dermal absorption studies are not designed to study the irritation or corrosion potential of substances, also the skin and eye irritation studies performed with the structural analogue, SDMC, were taken into account.

In the skin irritation study with SDMC, 0.5 ml of a 41% aqueous solution was administered to the clipped skin of dorsal/flank area of three New Zealand White rabbits under occlusive conditions (SafePharm Laboratories Limited, 2001a). Four hours after the application the dressing was removed and the residual test material was removed by gentle swabbing with cotton wool soaked in distilled water. Animals were observed for 72 hours. Well-defined erythema (average score 2) was noted at all treated skin sites one hour after patch removal and persisted at the 24-hour observation with very slight erythema at the 48-hour observation (score 1 in one animal). Slight to moderate oedema was noted at all treated skin sites one hour after patch removal (average score 2.7) with very slight to slight oedema at the 24-hour observation (average score 1.3) and very slight oedema persisting at one treated skin site at the 48-hour observation (score 1 in one animal). All treated skin sites appeared normal at the 72-hour observation. The results showed that SDMC is not irritating to rabbit skin.

In the eye irritation study with SDMC, 0.1 ml of a 41% aqueous solution was instilled in one eye of 3 New Zealand White rabbits, with untreated eye serving as concurrent control (SafePharm Laboratories Limited, 2001b). Animals were observed for 7 days and the irritation reactions were scored using the system of Draize. No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment (average conjunctiva score 2, average chemosis score 1.6) with minimal to moderate conjunctival irritation at the 24 and 48-hour observations (average conjunctiva score 1.3 and average chemosis score 0.3 at 48 hours observation). Minimal conjunctival irritation was noted in one treated eye at the 72-hour observation (conjunctiva and chemosis scores of 1 in one animal). Two treated eyes appeared normal at the 72-hour observation and one treated eye appeared normal at the 7-day observation. Discharge from the nose and mouth was noted in one animal at the 24, 48 and 72-hour observations. Based on the results of the study, it is concluded that SDMC in its marketed form is not irritating to eyes.

 

Taking into account the results of the three studies and using precautionary principle, it is considered acceptable to conclude that SDEC in its manufactured form (as 26% aqueous solution) should be regarded as irritating to skin and eyes. Considering very low acute oral toxicity of SDEC (LD50 > 5000 in 19.4% aqueous solution), it does not appear likely that the substance in its manufactured and marketed form (as 26% solution) can be corrosive. No additional studies are thus considered scientifically justified in accordance with Column 2 of REACH Annex VII. It should be noted that no information on skin irritating properties of the pure (anhydrous) substance can be derived from these results.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation: based on the results of the skin penetration study and using a precautionary principle, the substance should be classified as irritating to skin (Xi, R38) according to EU Directive 67/548/EEC. According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 it should be classified as Category 2, H315 (causes skin irritation).

Eye irritation: based on the results of the skin penetration study and using a precautionary principle, the substance should be classified as irritating to eye (Xi, R36) according to EU Directive 67/548/EEC. According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 it should be classified as Category 2, H319 (causes serious eye irritation).

It should be stated that this classification and labeling are not applicable for the isolated substance; however, as the substance is solely manufactured and marketed as saturated (26%) aqueous solution, the classification as reported above is considered to be acceptable.