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Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Remarks:
expert statement
Type of information:
other: expert statement
Executive summary:

No specific study was performed on the absorption, distribution, metabolism, excretion (ADME) of this substance (WS400301), but data are currently available fromin vivoandin vitrotoxicology studies.

 

The substance, WS400301, is the salt of dimethylcyclohexanamine and phosphoric acid with molecular weights of 127 Da and 98 Da, respectively. The substance is well water soluble (> 1000 g/L) and accordingly has low lipophilicity (Log10Pow for dimethylcyclohexanamine ranges from < 1 to 4.1 between pH values from 4 to 9, respectively).

It is expected (and was confirmed in bridging studies) that the salt dissociates in aqueous environments. Accordingly, exposure of man and the environment will be to phosphate ions and dimethylcyclohexanamine.

Different inorganic phosphate salts are used as direct food additives, e.g. E 339, 340, 341, 343, because of their low toxicological potential. Therefore, any adverse effects of WS400301 will be based on toxic properties of dimethylcyclohexanamine.

 

After oral exposure to WS400301 absorption of dimethylcyclohexanamine and systemic distribution is to be expected based on the low molecular weight and high water solubility. In the repeat dose feeding study with the read-across source substance dimethylcyclohexanamine some effects on organ weights (not considered as adverse) were observed indicating systemic distribution. At the highest dose level very likely palatability reasons lead to reduced food intake and body weight gain.

In the acute oral toxicity study performed in rats with the read-across source substance, i.e. dimethylcyclohexanamine, the LD50 was derived at a dose of approx. 290 mg/kg body weight. This value very likely was based not only on oral exposure to the substance but also was due to corrosive and irritating effects caused by dimethylcyclohexanamine as was observed in the stomach of dead animals (which in addition enhanced systemic availability of the substance).

Systemic availability of WS400301 after dermal application is expected to be low based on its hydrophilicity. However, in the acute dermal toxicity study performed with the read-across source substance dimethylcyclohexanamine relatively high toxicity (LD50 380 mg/kg) was observed. It is rather likely that this dermal toxicity was (also) due to severe corrosivity of dimethylcyclohexanamine observed after 24 hour occlusive exposure animals (which in addition enhanced systemic availability of the substance).

Availability of WS400301 under a vapour state will be very limited, because of its low vapour pressure (0.01 Pa at 20°C) and because it is a viscous liquid substance limiting its availability as an inhalable aerosol.

There is no information on metabolism and excretion of WS400301.

Bioaccumulation of WS400301 is very unlikely based on the high hydrophilicity.

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100

Additional information

No specific study was performed on the absorption, distribution, metabolism, excretion (ADME) of this substance (WS400301), but data are currently available fromin vivoandin vitrotoxicology studies.

 

The substance, WS400301, is the salt of dimethylcyclohexanamine and phosphoric acid with molecular weights of 127 Da and 98 Da, respectively. The substance is well water soluble (> 1000 g/L) and accordingly has low lipophilicity (Log10Pow for dimethylcyclohexanamine ranges from < 1 to 4.1 between pH values from 4 to 9, respectively).

It is expected (and was confirmed in bridging studies) that the salt dissociates in aqueous environments. Accordingly, exposure of man and the environment will be to phosphate ions and dimethylcyclohexanamine.

Different inorganic phosphate salts are used as direct food additives, e.g. E 339, 340, 341, 343, because of their low toxicological potential. Therefore, any adverse effects of WS400301 will be based on toxic properties of dimethylcyclohexanamine.

 

After oral exposure to WS400301 absorption of dimethylcyclohexanamine and systemic distribution is to be expected based on the low molecular weight and high water solubility. In the repeat dose feeding study with the read-across source substance dimethylcyclohexanamine some effects on organ weights (not considered as adverse) were observed indicating systemic distribution. At the highest dose level very likely palatability reasons lead to reduced food intake and body weight gain.

In the acute oral toxicity study performed in rats with the read-across source substance, i.e. dimethylcyclohexanamine, the LD50 was derived at a dose of approx. 290 mg/kg body weight. This value very likely was based not only on oral exposure to the substance but also was due to corrosive and irritating effects caused by dimethylcyclohexanamine as was observed in the stomach of dead animals (which in addition enhanced systemic availability of the substance).

Systemic availability of WS400301 after dermal application is expected to be low based on its hydrophilicity. However, in the acute dermal toxicity study performed with the read-across source substance dimethylcyclohexanamine relatively high toxicity (LD50 380 mg/kg) was observed. It is rather likely that this dermal toxicity was (also) due to severe corrosivity of dimethylcyclohexanamine observed after 24 hour occlusive exposure animals (which in addition enhanced systemic availability of the substance).

Availability of WS400301 under a vapour state will be very limited, because of its low vapour pressure (0.01 Pa at 20°C) and because it is a viscous liquid substance limiting its availability as an inhalable aerosol.

There is no information on metabolism and excretion of WS400301.

Bioaccumulation of WS400301 is very unlikely based on the high hydrophilicity.