1,4-diethylbenzene

Endpoint summary

Description of key information

No studies are available. When the physicochemical properties of 1,4-Diethylbenzene were assessed for toxicokinetic properties, the substance was expected to be easily absorbed from the gastro-intestinal tract. On the other hand, respiratory deposition and absorption as well as dermal absorption were assessed to be very low. The latter was confirmed by calculation of the dermal flux, which was very low (1.46.10-3 mg/(cm2.h)). Distribution in the body is expected to take place rapidly, mainly based upon the low molecular weight and the clinical observations and target organs seen in the toxicity studies.  
Limited data were available for estimation of metabolism (e.g. increased liver weights rats, which may be indicative of adaptive enzyme induction for breakdown).  Hydrolysis data  showed  that the substance is stable at different pH values. From the Manometric Respirometry Test it was concluded that the test item was not readily biodegradable.  Bioaccumulation is not expected, mainly based on the fact that BCF values were well below the trigger value for a PBT. Finally, several routes of excretion (e.g. urine, saliva, sweat, breast milk) were assessed to be possible, based on the physicochemical properties.  

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

90

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

30

Additional information

Discussion

The assessment below is based on the ECHA Guidance on information requirements and chemical safety assessment (Chapter R.7c: Endpoint specific guidance, November 2012 Version 1.1), for which physicochemical data may be used for a qualitative TK assessment. Most of the data needed were found in the OECD SIDS Initial assessment report on 1,4-Diethylbenzene (SIAM 2, Paris, 1994) and MSDS (Sigma Aldrich, Sicherheitsdatenblatt, 17.10.2012). Other data were based on specific study reports and literature references.

 

Absorption of 1,4-Diethylbenzene was assessed as follows based on physicochemical/toxicological data. The substance is a liquid compound with a molecular weight of 134.22 g/mol and water solubility of 17 mg/L. The logPow has a value of 4.06. The vapour pressure is 140.52 Pa. Hydrolysis data showed that the substance is stable at different pH values, and the substance is not readily biodegradable in the Manometric Respirometry test.

 Oral/GI absorption:            
The compound is not ionisable and has a low molecular weight, which favours oral absorption. The water solubility is quite low, which would limit oral absorption, however since the molecular weight is lower than 200 g/mol the substance can pass through the aqueous pores. Because of the high log Pow value (>4) the compound can also be taken up by micellular solubilisation. Furthermore the observed toxicity in acute oral toxicity studies indicates a good systemic availability of the substance underlining an oral absorption. Therefore the substance is expected to be easily absorbed from the gastro-intestinal tract.

 Respiratory absorption:
Based on the low vapour pressure there might not be a high amount of inhalable substance. However if some of the substance is inhaled, it can (theoretically) be expected to reach the lower respiratory tract due to the high lipophilicity. In practice, exposure is assumed to be very low based on the low vapour pressure.

Dermal absorption:

Based upon the fact that the substance is a liquid with a low molecular weight and showing skin irritation, the substance might be expected to be absorbed by the skin. However the low water solubility might prevent the substance to partition from the stratum corneum into the epidermis. Also the log Pow >4 might limit the rate of transfer between the stratum corneum and the epidermis. When QSAR data were taken into consideration (Dermwin; Version 2.01), the dermal penetration rate seems to be quite high. A dermal penetration rate of 0.14 cm/h was found, however because of the low water solubility, the value of the maximum dermal flux is rather low: 1.46.10^-3mg/(cm².h) or 0.00146 mg/(cm².h). Taking all this into account, dermal absorption is considered to be very low.

For the assessment of distribution, metabolism and excretion, physicochemical and toxicological properties are also taken into account according to ECHA guidanceChapter R.7c. 

Distribution:
Based upon the molecular weight below 200 g/mol, moderate water solubility of 17 mg/L and high LogP of 4.06, distribution in the body is expected to take place rapidly. This is further confirmed by the presence of clear target organ findings (liver and kidney changes) and clinical observations (including decrease of spontaneous motor activity) in the toxicity studies.

Metabolism and accumulation potential:
Metabolism cannot be deduced from the data available, except for the increase in liver weights in male and female rats dosed at 750 mg/kg in the repeated dose toxicity study, which may be indicative of adaptive enzyme induction for breakdown of the substance. The adipose tissue and the stratum corneum of the skin may be sites of accumulation, howeverbased on the very low dermal absorption, accumulation is not expected.     

Regarding bioacummulation potential,hydrolysis data showed that the substance is stable at different pH values. From the Manometric Respirometry Test it was concluded that the test item 1,4-Diethylbenzenewas not readily biodegradable.The BCF values lied between 320 and 629 L/kg, which is well below the trigger value of 2000 L/kg for a PBT substance as indicated by the REACH Guidance. Therefore, the substance is not expected to bioaccumulate in the body.

Excretion:
Based on the low molecular weight and moderate water solubility, (partly) urinary excretion of parent substance and metabolites are assumed. Excretion via the saliva and sweat are possible based on the high logPow value (>4). Also exfoliation may be applicable. Excretion in the breast milk is considered to be possible as well. Therefore several routes of excretion are available to reduce the substance in the body.