Vinyltoluene

Endpoint summary

Description of key information

A toxicokinetic assessment was conducted in accordance with REACH Annex VIII 8.8.1. The substance vinyl toluene is a colourless transparent organic liquid. It is ≥99.2% pure and consists of 64.3% meta-toluene (CAS No. 100-80-1) and 35.7% para-toluene (CAS No. 622-97-9).

 

A full ADME toxicokinetic study in the rat is not available. The toxicokinetic analysis is based on data from physicochemical data and in vivo animal models. In vivo studies covering the oral (acute toxicity in rats) and dermal routes (skin sensitisation in guinea pigs) are available. An acute and sub-chronic inhalational toxicity study in the rat is available. Further details on endpoints are available in the IUCLID 6 registration dossier.

 

Based on the physicochemical properties and information in the dossier, vinyl toluene is expected to be absorbed after oral, dermal and inhalation exposure. Vinyl toluene may be distributed, metabolised and is likely to be excreted in the urine. The absorption rates of 50% (oral), 50% (dermal) and 100% (inhalation) are accepted for chemical risk assessment purposes.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Physicochemical properties

In accordance with the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7C Section R.7.12 (Endpoint Specific Guidance), the physicochemical properties can provide an insight into the potential behaviour of vinyl toluene in the body.

 

Absorption

The molecular weight of vinyl toluene is 118 g/mol and is in the range for favourable oral absorption (<500 g/mol). The log Pow of vinyl toluene (3.38) indicates it is lipophilic and water solubility (89 mg/L at 25°C) indicates it is slightly soluble in water. These characteristics will facilitate transport of vinyl toluene via passive diffusion.

 

The water solubility (89 mg/L at 25°C) indicates low to moderate dermal uptake while the log Pow (3.38) is favourable for dermal absorption. Overall, the physical state, molecular weight, log Pow and water solubility indicate that some dermal absorption is likely.

 

Based on the vapour pressure of vinyl toluene (199 Pa at 20°C) and physical state (liquid), exposure via the inhalation route is expected.

 

Distribution/Metabolism/Excretion

The molecular weight (118 g/mol) and log Pow (3.38) of vinyl toluene are somewhat favourable for wide distribution. Based upon the molecular weight of 118 g/mol and water solubility, it is likely that vinyl toluene metabolites are excreted mainly in the urine.

 

Information from studies in the dossier

 

Absorption

Oral/GI absorption

Vinyl toluene has low toxicity via the oral route, based on QSAR and in vivo rat data (LD50>2000 mg/kg bw). For chemical safety assessment purposes, based on the physicochemical properties and information in the dossier, an oral absorption rate of 50% is accepted.

 

Dermal absorption

In an in vivo guinea pig maximisation test (GPMT; OECD 406/GLP), vinyl toluene was not a skin sensitiser. The ECHA guidance criteria (Chapter R.7C) state that 10% dermal absorption is used when the molecular weight of the substance is >500 and the log Pow is <-1 or >4, otherwise 100% dermal absorption is used. The molecular weight of vinyl toluene is 118 g/mol and the log Pow is 3.38, so a dermal absorption rate of 100% would be applicable. However, in general, dermal absorption will not be higher than oral absorption, so for chemical safety assessment purposes a dermal absorption rate of 50% is accepted.

 

Respiratory absorption-Inhalation

In an acute toxicity study in rats, the LC50 male/female was > 5.02 mg/L air (OECD 403/GLP). 

In a sub-chronic inhalation toxicity study, vinyl toluene was administered to 10 male and female F344/N rats by dynamic whole body inhalational exposure at concentrations of 0, 25, 60, 160, 400, or 1,000 ppm for 6 hours per day, 5 days/week for a total of 13 weeks (Similar to OECD 413/GLP). All rats lived to the end of the studies. The final mean body weights of rats exposed to 160, 400, or 1,000 ppm were 6%, 8%, or 19% lower than that of controls for males and 5%, 6%, or 12% lower for females. Excessive lacrimation, palpebral closure, and rough hair coats were seen in rats exposed to 1,000 ppm. Relative liver weights, but not absolute weights, for rats exposed to 1,000 ppm were significantly greater than those for controls, but were not associated with histopathological changes. A mild nephropathy characterized by increased tubular casts was found in male rats exposed to 160, 400, or 1,000 ppm. No compound-related lesions were observed in female rats. There were no reports of local effects. The NOAEC value of both sexes was considered to be 60 ppm (289.57 mg/m3 based on molecular weight of 118 g/mol). The LOAEC value for both sexes was considered to be 160 ppm.

The in vivo vinyl toluene data together with the physicochemical information indicates that vinyl toluene is absorbed via the inhalational route. For chemical safety assessment purposes, an inhalation absorption rate of 100% is accepted.

 

Distribution/Metabolism/Excretion

In the sub-chronic inhalation toxicity study, a mild nephropathy was noted in male rats only at 160, 400, or 1,000 ppm and this effect on the kidney may affect excretion.