Methanaminium, N-[4-[[4-(dimethylamino)phenyl]phenylmethylene]-2,5-cyclohexadien-1-ylidene]-N-methyl-, ethanedioate

Endpoint summary

Description of key information

Oral toxicity: LD50 < 2000 mg/kg bw

Dermal toxicity: LD50 > 2000 mg/kg bw

Inhalatory exposure is unlikely.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

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

Value:

2 000 mg/kg bw

Additional information

ACUTE TOXICITY - ORAL ROUTE

The oral acute toxicity of Malachite Green was mainly tested in rats. The available data report LD50 values for rats in the range of 275 - 1400 mg/kg bw. Unfortunately, details about the lot composition tested in the two experimental investigation (DyStarColours Distribution GmbH 1983) and in the Meyer and Jogenson (1983) publication are missing. Only in the case of Clammensen et al (1984) a test substance purity higher than 90 % is stated.

In the Clammensen et al (1984) publication is also indicated that mice seemed to be more sensitive than rats, as range-finding for the micronucleus test showed that approximately half of the animals died at a dose of 50 mg/kg.

Despite the low reliability of the available data, the substance showed evident toxicity if swallowed.

An harmonized classification and labelling (C&L) has already been approved for Malachite Green chloride (EC: 209-322-8) and oxalate (EC: 219-441-7) salts. The classifications have been discussed by Commission of the European Communities and the related information was presented in ECBI/54/02 report, 18th July, 2002 (Health and Safety Executive, UK. 2005). The oral acute toxicity assessment was based on the Clemmensen et al. (1984) and Meyer and Jorgenson (1983) publications and the conclusion was that the data available support the current classification as Xn; R22. It has to be note that criteria to classify a substance as harmful if swallowed are different for Directive 67/548/EEC (DSD) and EC Regulation 1272/2008 (CLP): for LD50 value a range of 200-2000 and of 300-2000 is stated, respectively. However, the harmonized classification arranges both salts oxalate and chloride in category 4, for acute oral toxicity (H302), of the CLP Regulation; it can be concluded that a re-classification has not been considered as appropriated.

In conclusion, taking into account the available data and the harmonized C&L of the analogous salts Malachite Green oxalate (EC: 219-441-7) and Malachite Green hydrochloride (EC: 209-322-8), a classification as Acute tox. 4 (H302), according to the CLP Regulation (EC 1272/2008), is proposed.

ACUTE TOXICITY - INHALATION ROUTE

No acute toxicity studies by inhalation route are available on Malachite Green. Nevertheless, because of the physical state and the trade forms of the substance inhalation is not an appropriate route of exposure. Particle size distribution (DyStarColours Distribution GmbH, 2011) showed that Malachite Green is characterized by particles that are expected to remain in the upper respiratory tract, which has efficacious defence mechanisms able to remove them. The analysis recorded that the 90 percent of particles have a diameter lower than 184 µm, the 50 percent have a diameter lower than 68 µm and the 10 percent have a diameter lower than 13 µm. In particular, only about 2.6 % of particles have a diameter lower than 5 µm. From this point of view, inhalation route is expected to be an unlikely route of absorption of the substance.

Despite the real importance of the following observation cannot be evaluated, it should be mentioned for completeness sake that in the study on teratogenical effects on rabbits and published by Meyer and Jorgenson (1983) the authors reported that some animals died for acute pulmonary toxicity, within minutes after the test item aspiration into the lungs. It should also be taken into account that there are no informations about the test substance composition and that the effects cannot be certainly attributed to Malachite Green.

ACUTE TOXICITY - DERMAL ROUTE

Currently, according to the REACH Regulation annex VIII column 2 (specific rules for adaptation from column 1) testing by the dermal route is appropriate if inhalation of the substance is unlikely; and skin contact in production and/or use is likely; and the physical/chemical and toxicological properties suggest potential for a significant rate of absorption through the skin.

The inhalation of Malachite Green is unlikely, nevertheless also the skin contact is unlikely. Because of the physical/chemical properties of the substance the dermal absorption is expected as not significant, from a systemic acute toxicity point of view. The investigation performed on both Malachite Green Oxalate and Chloride concluded that dermal absorption can be considered as negligible; after 24 hours the 92 % of Malachite Green oxalate resulted to be unabsorbed (REACH&colours Kft, 2011).

Clemmensen et al (1984) publication reports that no signs of systemic toxicity were observed after occlusive dermal application of 2000 mg/kg: the 20 % suspension of Malachite Green did not produce visible erythema or oedema on either rats and guinea pigs.

REFERENCE

Health and Safety Executive, UK. June 2005. ECBI/35/05. Commission of the European Communities. Classification and labelling of dangerous substances. Recommended form to be used for the proposed classification and labelling of Dangerous Substances in order to update Annex 1 of Directive 67/548/EEC.

Justification for selection of acute toxicity – oral endpoint

Conclusion based on a weight of evidence approach, taking into account all the available information.

Justification for selection of acute toxicity – inhalation endpoint

Because of the physical state and the trade form of the substance, inhalation is not an appropriate route of exposure.

Justification for selection of acute toxicity – dermal endpoint

Conclusion based on a weight of evidence approach, taking into account all the available information.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be approximately in the range of 300 - 2000 mg/kg body weight, therefore the classification as harmful if swallowed is proposed (Acute Tox. 4, H302).

The dermal LD50 value was established to be higher than 2000 mg/kg body weight, which exceeded the highest CLP limit for classification (dermal acute toxicity category 4: 1000 < ATE ≤ 2000 mg/kg bw).

In conclusion, the test substance is classified as Acute Tox. 4 (H302) for oral route of exposure; on the contrary, it is non classified for dermal acute toxicity, according to the CLP Regulation (EC 1272/2008).