2-(4-chlorobenzoyl)benzoic acid

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

There are no published data which could be identified on the toxicokinetics of the substance. However, as per REACH guidance document R7. C (June 2017), information on absorption, distribution, metabolism and excretion may be deduced from the physico-chemical properties including:

-       Water solubility

-       Partition coefficient

-       Vapour pressure

-       Molecular weight

Oral absorption

Based on physico-chemical properties:

According to the REACH guidance document R7.C (June, 2017), oral absorption is maximal for substances with molecular weights below 500. Water-soluble substances will readily dissolve into the gastrointestinal fluids; however absorption of hydrophilic substances via passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Further, absorption by passive diffusion is higher at moderate log Kow values (between -1 and 4). If signs of systemic toxicity are seen after oral administration (other than those indicative of discomfort or lack of palatability of the test substance), then it could be assumed that absorption has occurred to some extent.

The test substance is a mono-constituent with a molecular weight (MW) below 500 g/mol. It is a solid with a moderate water solubility 136 ± 3.6 mg/L and an experimental log Kow ranging from 0 to 1. Volatility was determined to be low (based on vapour pressure of 2.23E-6 Pa at 20°C).

Based on the R7.C indicative criteria, oral uptake of the test substance is assessed to be high, given the low MW and moderate water solubility.

Conclusion: Overall, based on all the available weight of evidence, the test substance can be expected to have a high absorption through the oral route. However, in absence of experimental data, a default value of 50% has been considered for the risk assessment.

Dermal absorption

Based on physico-chemical properties:

According to REACH guidance document R7.C (May 2014), dermal absorption is maximal for substances with molecular weights below 500 and log Kow values ranging between 1 and 4. The test substance has MW below 500 g/mol and the measured log Kow of the test substance is in the range of 0 – 1. Therefore, along with the moderate water solubility, this suggests that the substance may penetrate the skin moderately.

Based on QSAR prediction:

It has been suggested that if Kp <10E-3 cm/h (or 0.01 cm/h), low skin penetration will be assigned (Michael and Kenneth, 2007). The Kp value of the test substance is 0.00882 cm/hr and, therefore, is predicted to be absorbed moderately.

Conclusion: Physico-chemical properties and QSAR predictions suggest that the test substance will be absorbed moderately via skin, therefore a default value of 100% has been assumed for a conservative risk assessment.

Inhalation absorption

Based on physico-chemical properties:

According to REACH guidance document R7.C (May 2014), inhalation absorption is maximal for substances with VP >25 KPa, particle size (<100 μm), low water solubility and moderate log Kow values (between -1 and 4). Very hydrophilic substances may be retained within the mucus and not available for absorption.

The test substance, because of its relatively low vapour pressure of 2.23E-6 Pa at 20°C, will not be available as vapour for inhalation under ambient conditions. Further, if at all there is any inhalation exposure, considering its physico-chemical properties (such as moderate water solubility)) penetration into lower respiratory tract is not expected. 

Conclusion: Overall, based on all the available weight of evidence, the test substance can be expected to have low absorption through the inhalation route. However, in absence of experimental data, a default value of 100% has been considered for the risk assessment.

Metabolism

Based on QSAR modelling:

The predicted metabolism of the test substance was evaluated using thein vivorat metabolism and rat liver S9 metabolism simulators of the OECD QSAR Toolbox v.3.4. According to these simulators, the test substance is predicted to undergo reduction.

 

	Test substance
Rat liver S9 metabolism simulator andin vivorat metabolism simulator	Predicted metabolites:

 

Bioaccumulation:

Based on the physico-chemical information (log Kow within the range 0 to 1) and BCF of 3.16 it is concluded that the potential for bioaccumulation is low.

Excretion:

Based on the low MW and moderate water solubility, the test substance is expected to be excreted via urine.