(4-nonylphenoxy)acetic acid

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 278.4 g/mol) is a clear, yellow to brown viscous liquid (BASF, 2012) with a water solubility of 0.04 g/L (Ciba-Geigy, 1985) and a vapor pressure of 0.0025 Pa at 25°C (Ciba-Geigy, 1985). The log Pow was calculated to be 5.8 for the neutral, undissoziated form (EPI Suite, BASF, 2012), and is further characterized by pH dependency, ranging from 4.6 at pH 4 to 1.7 at pH 9 (SciFinder, 2011).

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 at physiological conditions 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 systemic effects in the high dose group. The weights of liver and thyroid glands were increased and kidneys in males were increased slightly. 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 corrosive nature of the test article, uptake after dermal exposure is expected to be increased due to the damage of dermal tissue. This is in line with the results obtained in a guinea pig maximization test. Here, the test article was shown to cause skin sensitization after dermal exposure, indicating its potential to cross the dermal barrier.

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 liquid with a low vapor pressure; therefore its availability for inhalation is expected to be low.

Metabolism

In an Ames and an HPRT test, the test article did not produce an increase in revertant colonies in the presence of a metabolizing agent, therefore no conclusion can be drawn regarding in vitro metabolization. In the available repeated dose toxicity study increases in liver and kidney weights were observed in high dose animals. This often correlates with an increased workload due to administration of the test article indicating that the test article is metabolized in the liver. However, the test article also caused increases in thyroid gland weights and disturbance of T4 levels, which might be due to a rat specific enzyme induction in the liver.

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.