Dichlone

Endpoint summary

Additional information

Assessment of the toxicokinetic behavior

No studies are available investigating the toxicokinetic properties of the test substance.The test substance (molecular weight of 227 g/mol) is a clear, yellow powder (Chilworth, 2015) with a water solubility of 2.1 mg/L (BASF, 2014) and a vapor pressure of 0.00022 Pa at 25°C (BASF, 2015). The log Pow was determined to be 2.9 at a pH of 6.1 (BASF, 2014).

Absorption

Absorption via the gastrointestinal tract:

Absorption through the gastrointestinal tract is favored for molecules with a molecular weight below 500 g/mol (ECHA GD 7c, 2008), thus the test article’s molecular weight is favorable for absorption after oral exposure. Further criteria in favor of absorption are hydrophilicity and a moderate log P_OW value (between -1 and 4). The test article is hydrophobic and therefore not very soluble in aqueous solutions. However, the moderate log P of the test article is in favor of absorption. In a combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats, treatment with the test item caused adaptive systemic effects in the high dose group, i.e. the weights of kidneys were increased. In conclusion, gastrointestinal absorption takes place as shown by the in vivo data obtained in the repeated dose study.

 

Dermal absorption:

Dermal uptake is favored for chemicals with a molecular weight < 100 g/mol, while for chemicals with a molecular weight > 500 g/mol, dermal uptake is not favored (ECHA GD 7c,2008). In addition, Log P values between 1 and 4 favor dermal absorption. Given the irritating nature of the test article, uptake after dermal exposure is expected to be increased due to the damage of dermal tissue. However, the acute LD50 study revealed an LD50 of > 2000 mg/kg with no mortalities, whereas the substance is classified for acute toxicity by the oral route with LD50 values ranging from 160 mg/kg to 1300 mg/kg. These data indicate that absorption through the skin might be less potent than by the GI tract.

Absorption via inhalation:

No experimental data from acute or repeated dose inhalation toxicity studies are available, which could provide information about the systemic distribution of the test substance after inhalation. The test article is a powder with a low vapor pressure. 20% of particles were determined with a size of < 10µm, therefore this fraction can reach the alveolar region. Absorption is likely to occur due to the log Pow of 2.9, which favors absorption directly across the respiratory tract epithelium by passive diffusion.

Metabolism

In various genotoxicity studies, the test article did not produce an increase in revertant colonies in the presence of a metabolizing agent, therefore there is no indication for metabolic activation.

Excretion

Smaller molecules (< 300 g/mol) tend to be excreted in the urine, especially when they are soluble in water. Larger molecules are expected to be eliminated via biliary excretion. The test substance has a molecular weight of < 300, therefore allowing for excretion via the urine. However, this pathway might be limited by the low water solubility, therefore excretion might occur via feces. Potential metabolites might be excreted via urine or feces, depending on size and water solubility after metabolic breakdown and phase II metabolism.