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Description of key information

Key value for chemical safety assessment

Additional information

1. Physical-chemical properties

DMDC (MW 238.4 g/mol) is a colorless/yellowish liquid with a measured melting point of -7.1°C, a measured boiling point of 342°C at 1013 hPa, a measured vapour pressure of 0.08 Pa at 20°C, a water solubility of 3.6 g/l at 20ºC and a dissociation constant (pKa) of 10.67. The octanol-water partition coefficient (log Pow) is 2.51 at 25°C.

 

2. Data from mammalian toxicity studies

The systemic effects after acute and repeated dose oral, inhalation and dermal exposure show that the substance becomes bioavailable and reaches different organs.

 

The acute oral study did not show clear systemic effects (BASF AG, 1979a). However, a well-conducted subchronic oral toxicity study and a developmental toxicity study (both with rats) showed that the substance caused systemic effects (see below).

At gross necropsy, effects on the heart (acute dilatation of the right ventricle, acute congestive hyperemia) were observed in the acute inhalation study (BASF AG, 1979b). The well conducted rat 90-day inhalation study showed more clearly that the substance becomes bioavailable and reaches different organs (see below).

In the acute dermal toxicity study, the following systemic effects were observed: cyanosis, apathy, dyspnea, accelerated breathing, abdominal position with flaccid extremities, lateral position, trembling. In addition, gross necropsy revealed effects on the heart (acutely dilated, right; acute congestion), lungs (notable congestion, in some animals edematised) and liver (gray-white lobular periphery broader) (BASF AG, 1979c).

 

In a well conducted rat 90-day inhalation study (OECD 413) body weight development was impaired, local irritative effects observed for the skin and upper airways (nasal mucosa) and target organ toxicity indicative of a mild anemic effect as well as effects on the liver, testes and kidneys were seen at 48 mg/m3 (BASF AG, 1992a). No histopathological correlate was found with respect to increased absolute lung weights.

At 12 mg/m3 the marginal increase in GPT level was not considered toxicologically relevant in the absence of an increase in GOT levels and any effects in the liver. Therefore, the NOAEC was set at 12 mg/m3.

In a subchronic oral toxicity study with rats (OECD TG 408), the animals were exposed to 0, 2.5, 12 and 60 mg/kg bw/day by gavage over 3 months. Liver, white and red blood cells, kidneys, adrenal glands and heart were the target organs for toxic effect, showing also histopathological alterations. At the high dose level (60 mg/kg bw/day) body weight development/food consumption was clearly impaired and the general state of health was poor. The absolute testes weight was decreased and an atrophy of the seminiferous tubuli and a reduced content of the seminal vesicle were noted. These changes were interpreted as consequence of the marked impairment on body weight. While the toxic effects at the mid dose of 12 mg/kg bw/day were generally less pronounced, a NOAEL was achieved at 2.5 mg/kg bw/day (BASF AG, 1990b).

In a developmental toxicity study (OECD TG 414 and GLP) DMD (0, 5, 15 or 45 mg/kg bw/day) was administered from day 6 to 19 post-coitum orally by gavage to rats (BASF AG, 2001). Several macroscopic findings in the liver (i.e. paleness, accentuated lobular pattern and/or whitish areas) were observed at 45 mg/kg bw/day.

In the dose range finding study of the developmental toxicity study, pregnant female rats were administered daily from day 6 to day 19 post-coitum (BASF AG, 2002). Slight maternal toxic effects were reported at 50 mg/kg bw/day. At 100 mg/kg bw/day, marked maternal toxicity was recorded, with forestomach, stomach and liver as target organs. The 200 mg/kg bw/day dose-level was dramatically maternal toxic (non-specific signs of poor clinical condition, signs of gastro-intestinal intolerance, respiratorydisorders; severe body weight loss and reduction of food consumption). All surviving high-dose dams were sacrificed in moribund condition before schedule on day 10 post-coitum.

 

3. Absorption, distribution, metabolism, excretion

No studies on toxicokinetics, metabolism and distribution are available. However, the results from the studies described above show that the compound can be absorbed via the skin, the lung and the intestinal tract. Nevertheless, internal exposure through dermal contact was calculated using IH SkinPerm model (AIHA) showing a maximal dermal absorption of 0.00257 mg/cm2/h.