Reaction product of 2,4-Dinitrotoluene and 2,6-Dinitrotoluene and hydrogen

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Assessment of the Toxicokinetic Behaviour

The registered substance is a reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen (common name: diaminomethylcyclohexane, MDACH, or MCDA, respectively) consisting of the two isomers 4 -methylcyclohexane-1,3-diamine (CAS 13897-55-7; molecular weight approx. 128 g/mol) and 2-methylcyclohexane-1,3-diamine (CAS 13897-56-8; molecular weight approx. 128 g/mol). Both of which have an estimated log Kow less or equal to 3. It is a clear, colourless liquid miscible with water at room temperature (T = 23°C) in any ratio. Its vapour pressure is estimated to be approx. 0.18 hPa at 20 °C.

The registered substance was tested in several toxicity studies, which were conducted on the one hand using 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7) which is the main isomer of the registered substance (up to 90%) and on the other hand the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen was tested as such (for details see read across justification, IUCLID chapter 13).

 

Absorption

An acute oral LD50 of approx. 1276 mg/kg bw (test substance:4-methylcyclohexane-1,3-diamine (CAS 13897-55-7)) was found in rats (Smyth et al. 1969). Additionally, signs of parental systemic toxicity were observed in rats in an oral combined repeated dose toxicity study with the reproduction / developmental toxicity screening test (OECD TG 422, BASF SE, 2011) from 100 mg/kg bw, while no signs of toxicity were found in a subchronic toxicity study (OECD TG 408, BASF SE, 2017) at the same dose level (test substance: reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen).

It is therefore assumed that the registered substance or its possible metabolites become systemically available after absorption along the gastro intestinal tract.

The registered substance is corrosive to the rabbit skin (BASF SE, 2011), and, probably as consequence of the induced local damage, may induce mortality after single skin contact (LD50 = 452.5 mg/kg bw; test substance: 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7); Smyth et al. 1969). When the salt of the registered substance was evaluated for acute dermal toxicity according to the OECD TG 402, no mortality nor clinical signs of toxicity were observed up to the dose level 3420 mg/kg bw.

It is unclear if the lack of general toxicity is due to low or no dermal absorption or due to the low toxicity of the test substance salt. It is however anticipated that the test substance, because of its corrosivity potential, may be able to penetrate the dermal barrier, and, therefore, become systemically bioavailable.

No mortality occurred in an inhalation risk test (test substance: 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7)), where the test animals (rats) were exposed to an atmosphere saturated with vapours of the test substance (Smyth et al. 1969; with limited documentation).

However, as conjectured above, a systemic availability of the registered substance after inhalation exposure cannot be ruled out because of its corrosive potential.

 

Distribution

At least the accessory sex glands (male animals) appeared to be possible target organs in the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test (test substance: reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen), although their reproduction performances were not affected (BASF SE, 2011).

Therefore, the substance was additionally tested to assess an androgenic and/or antiandrogenic activity by using the Yeast Androgen Screening Assay (YAS-Assay). The reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen did neither exert androgenic effects nor antiandrogenic effects in this test (BASF SE, 2012). Moreover, such effects on the accessory sex glands were not observed in an subchronic repeated dose toxicity study (OECD TG 408) up to the highest dosage tested (100 mg/kg bw) although special attentionwas given to the reproductive organs of male and female animals.

In view of the log Kow value, a general accumulation of the registered substance in adipose tissue may normally be unlikely with repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous.

 

Metabolism

Using the OECD toolbox vs.2.0, the liver metabolism simulator provided approx. 10 potential simulated metabolites for CAS 13897-55-7, and approx. 5 for CAS 13897-56-8, as well as approx. 5 and 10 simulated skin metabolites for CAS 13897-55-7 and CAS 13897-56-8, respectively.

The negative mutagenicity tests in the presence and absence of a metabolic activating system (Ames, HPRT, CA) further suggest that none of the possible metabolites (or the parent substance) is likely to induce genetic toxicity. No further are data available.

 

Excretion

No data available.

Based on the molecular weights of the main constituents and the water solubility, it is conjectured that the registered substance would probably primarily undergo a renal elimination.