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Description of key information

Acute oral LD50 in rats 444 mg/kg bw,  in cats and dogs 50-100 mg/kg bw. 
Acute dermal LD50 in rats >2000 mg/kg bw (no assay in other species available).
No mortality in rats and cats with highest technically feasible and respirable inhalation atmosphere.

Key value for chemical safety assessment

Additional information

Acute oral exposure:

The key study describing the oral toxicity of pure MDA in rats, resulted in a LD50 of 444 mg/kg bw (BASF, 1975). At a starting dose of 250 mg/kg bw, no mortalities or pathological effects have been observed. In a supporting study in rats similar LD50 values were determined, reaching from 350 to 480 mg/kg bw (Steinhoff, 1974). Damage to the liver and kidneys has been reported to be the most prominent toxic effect in rats.


Orally administered MDA has shown to induce severe changes in the liver of male Sprague-Dawley rats with a threshold of toxicity between 25 and 75 mg/kg. MDA caused changes in markers for liver injury, including serum ALT, bile flow, serum bilirubin concentration, GGT activity, and liver weight. Liver sections of 100 mg/kg bw animals exhibited multifocal lesions consisting of hepatocellular necrosis with hemorrhage and moderate infiltration in neutrophils (Bailie et al., 1993).


Cats and dogs are more sensitive to MDA exposure. After treatment with 100 mg/kg bw 7/11 cats and 3/3 dogs died. MDA induced ophthalmologic damage and damage of the liver and kidney beginning with 10 mg/kg bw in cats and 50 mg/kg bw in dogs (lowest doses tested). Mortality in both species occurred due to organs disorder (BASF, 1961). Methemoglobin (MetHb) levels were moderately elevated in cats (up to 17% with a dose of 100 mg/kg bw). Regarding the ability of MetHb-formation the cat was identified as the species most similar to human. Therefore a slight ability for MetHb in humans has to be expected, but no classification regarding effects on the hematopoetic system is indicated. Retinal damage was reported in surviving cats.


Acute dermal exposure:

Acute mortality on the dermal route of exposure was highly dependent on the solute of the tests substance (DMSO or water) and the sex of the animal. In the key study MDA was applied as a 50% aqueous solution as well as a 50% DMSO solution (Zeller & Hildebrand, 1976). While application of 2500 mg/kg bw MDA as a 50% aqueous solution caused no mortalities, 1000 mg/kg bw MDA as a 50% solution in DMSO killed 5 out of 10 female rats within 7 days. Male rats were not affected by treatment with 1000 mg/kg bw MDA in DMSO. A dose as high as 2000 mg/kg needed to be applied in order to kill male animals. Mortality increased dose dependently, resulting in an acute dermal LD50 value of 2080 mg/kg bw, with females being more susceptive than males. Apathy, hyperchromodacryorrhea, and jaundice as clinical signs of systemic toxicity have been observed in all treatment groups.

In another acute dermal toxicity, MDA was similarly applied as 3 -4 ml aqueous or DMSO formulation. No mortalities were observed applying aqueous solutions of MDA (LD50 >1000 mg/kg, highest concentration tested) in both sexes, and in males treated with MDA in DMSO. Female rats were more sensitive to MDA in DMSO solution resulting in a LD50 of 750-1500 mg/kg (Thyssen, 1976).


Acute inhalation exposure:

After exposure of rats for 6 h with 0.46 mg/l MDA no mortality occurred and animals were in good condition (BASF, 1977a). The same experimental design was used for an inhalation study in cats and also no mortalities occurred during a 6 h exposure with 0.1 mg/l MDA. However, one animal showed salivation and 2 animals vomited during exposure. All animals in this study showed yellowish sclera and conjunctiva which was reversible after 14 days in 5/6 animals (BASF, 1977b). In all tests gravimetrical determination of the particle size distribution was performed, showing that most of the dust particles were within the respirable fraction.



Human exposure:

Acute intoxication of humans with MDA is reported after oral, dermal and inhalation exposure, leading to jaundice. In addition to acute hepatic illness, in some cases myocardial effects and persistent retinal damage were reported.



Based on the animal data described, MDA is toxic after acute oral exposure (R25, GHS cat 3) and harmful in contact with skin (R21, GHS Cat 4). Though considerable dermal toxicity was only observed in presence of a solvent which can act as a carrier (DMSO).

From the animal data available for acute inhalation toxicity no classification is appropriate, since no severe signs of toxicity were reported.

Although due to severe liver toxicity of the substance at low dose levels (between 25 - 75 mg/kg), the test substance should be classified as a specific target toxicant Cat 1 (STOT single-dose Cat 1) and R39 based on GHS/EU standards.

Taking into account that rodents may not present the adequate model to predict acute toxicity of this substance to humans, human observations after several cases of acute poisoning at the workplace, and of consumers in 1965 (“Epping Jaundice”) need to be considered for classification. Since the substance is readily absorbed through the skin and the mucosa of the respiratory tract, classification as R39/23/24/25 (Toxic: danger of very serious irreversible effects through inhalation, in contact with skin and if swallowed) was agreed on the CMR Working Group Meeting, 7-9. October 1998. (STOT single Cat 1, causes damage to the liver on all routes of exposure). Furthermore irreversible damage of the retina should be taken into account.

Justification for classification or non-classification

For acute oral toxicity, cats and dogs are more sensitive than rats. The LD50 of 50 -100 mg/kg calls for an acute oral classification cat 3: HH301: toxic if swallowed.

Considerable dermal toxicity was observed only if the solvent DMSO was used, which acts as a carrier. Therefore, no classification for acute dermal toxicity is proposed.

Although the cut-off limits for acute inhalative toxicity according to regulation 1272/2008/EC were not exceeded, the highest technically feasible concentrations did not cause mortalities. No classification for acute inhalative toxicity is proposed.

Due to irreversible liver and retina effects, classification as STOT single exp. cat 1 (R39/23/24/25) is appropriate.