Diammonium 2,2'-dithiodiacetate

Endpoint summary

Description of key information

Experimental toxicokinetic studies are not available. The log Pow of  0.3 is suggestive of no accumulation potential of DADTDG. Furthermore, on the basis of the molecular structure excretion into urine as glucuronide or sulphate is assumed to be a preferred route of elimination. Elimination is assumed to be rapid. Therefore, no potential for bioaccumulation is to be expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

5

Absorption rate - inhalation (%):

45

Additional information

Assessment of oral toxicokinetics based on the physicochemical properties of DADTDG:

Molecular weight 216

Water solubility 629 g/L

Partition coefficient log Kow = 0.3

The following remarks on the toxicokinetics of DADTDG are based on the available studies. Experimental toxicokinetic studies were only available for the main metabolite, the thioglycolic anion.

 

ABSORPTION

The physicochemical characteristics of DADTDG (log Pow 0.3) and the molecular mass are in a range suggestive of absorption from the lungs and the gastro-intestinal tract subsequent to oral ingestion, respectively. This assumption of an oral absorption is supported by the Danish EPA QSAR database (% G.I. abs. for 1 mg dose) predicting an oral absorption of 50% following an administered dose of 1 mg.

The EpiSuite DermWin v2.02 program predicts a low dermal absorption of 0.0084 mg/cm²/event, but absorption via the skin could be pH-dependent.

 

DISTRIBUTION and METABOLISM

As a small molecule a wide distribution is expected. This assumption is confirmed by the changes shown in the repeated dose toxicity studies conducted with the main metabolite of DADTDG, the thioglycolate anion following oral application. Cleavage of the disulfide bond leads to two molecules of the main metabolite, the thioglycolate anion and the toxicity and metabolism of the anion is very well investigated in many single- and repeat-dose toxicity studies. These studies suggest that after cleavage of DADTDG to thioglycolate anions the anions will preferably be either directly conjugated in a phase-II reaction or will excrete directly via the urine. DADTDG itself is found to enter the urine shortly after systemic administration of the thioglycolate anion described in a review from 2009 (Burnett et al., 2009).

 

ELIMINATION

The n-Octanol/water partition coefficient (log Pow of 0.3) is not suggestive of accumulation of unchanged DADTDG in fatty tissues subsequent to absorption from gastrointestinaltract or from lungs. Furthermore, studies with the main metabolite suggest full metabolism of the thioglycolate anion to unconjugated DADTDG and suphate and subsequent excretion into urine. Elimination is shown to be rapid. Therefore, no potential for bioaccumulation is to be expected

Assessment of oral toxicokinetics based on the physicochemical properties of DADTDG:

Molecular weight 216

Water solubility 629 g/L

Partition coefficient log Kow = 0.3

The following remarks on the toxicokinetics of DADTDG are based on the available studies. Experimental toxicokinetic studies were not available.

 

ABSORPTION

The physicochemical characteristics of DADTDG (log Pow 0.3) and the molecular mass are in a range suggestive of absorption from the lungs and the gastro-intestinal tract subsequent to oral ingestion, respectively. This assumption of an oral absorption is supported by the Danish EPA QSAR database (% G.I. abs. for 1 mg dose) predicting an oral absorption of 50% following an administered dose of 1 mg.

The EpiSuite DermWin v2.02 program predicts a low dermal absorption of 0.0084 mg/cm²/event, but absorption via the skin could be pH-dependent.

 

DISTRIBUTION and METABOLISM

As a small molecule a wide distribution is expected. This assumption is confirmed by the changes shown in the repeated dose toxicity studies conducted with the main metabolite of DADTDG the thioglycolate anion following oral application. Cleavage of the disulfide bond leads to two molecules of the main metabolite, the thioglycolate anion and the toxicity and metabolism of the anion is very well investigated in many single- and repeat-dose toxicity studies. These studies suggest that after cleavage of DADTDG to thioglycolate anions the anions will preferably be either directly conjugated in a phase-II reaction or will excrete directly via the urine. DADTDG itself is found to enter the urine shortly after systemic administration of the thioglycolate anion described in a review from Burnett et al., 2009.

 

ELIMINATION

The n-Octanol/water partition coefficient (log Pow of 0.3) is not suggestive of accumulation of unchanged DADTDG in fatty tissues subsequent to absorption from gastrointestinaltract or from lungs. Furthermore, studies with the main metabolite suggest full metabolism of the thioglycolate anion to unconjugated DADTDG and suphate and subsequent excretion into urine. Elimination is shown to be rapid. Therefore, no potential for bioaccumulation is to be expected

Assessment of oral toxicokinetics based on the physicochemical properties of DADTDG:

Molecular weight 216

Water solubility 629 g/L

Partition coefficient log Kow = 0.3

The following remarks on the toxicokinetics of DADTDG are based on the available studies. Experimental toxicokinetic studies were not available.

 

ABSORPTION

The physicochemical characteristics of DADTDG (log Pow 0.3) and the molecular mass are in a range suggestive of absorption from the lungs and the gastro-intestinal tract subsequent to oral ingestion, respectively. This assumption of an oral absorption is supported by the Danish EPA QSAR database (% G.I. abs. for 1 mg dose) predicting an oral absorption of 50% following an administered dose of 1 mg.

The EpiSuite DermWin v2.02 program predicts a low dermal absorption of 0.0084 mg/cm²/event, but absorption via the skin could be pH-dependent.

 

DISTRIBUTION and METABOLISM

As a small molecule a wide distribution is expected. This assumption is confirmed by the changes shown in the repeated dose toxicity studies conducted with the main metabolite of DADTDG the thioglycolate anion following oral application. Cleavage of the disulfide bond leads to two molecules of the main metabolite, the thioglycolate anion and the toxicity and metabolism of the anion is very well investigated in many single- and repeat-dose toxicity studies. These studies suggest that after cleavage of DADTDG to thioglycolate anions the anions will preferably be either directly conjugated in a phase-II reaction or will excrete directly via the urine. DADTDG itself is found to enter the urine shortly after systemic administration of the thioglycolate anion described in a Cosmetic Ingredient Review from 2009 (Burnett et al.).

 

ELIMINATION

The n-Octanol/water partition coefficient (log Pow of 0.3) is not suggestive of accumulation of unchanged DADTDG in fatty tissues subsequent to absorption from gastrointestinaltract or from lungs. Furthermore, studies with the main metabolite suggest full metabolism of the thioglycolate anion to unconjugated DADTDG and suphate and subsequent excretion into urine. Elimination is shown to be rapid. Therefore, no potential for bioaccumulation is to be expected (Burnett et al., 2009).