Myrac Aldehyde

Endpoint summary

Description of key information

There were no studies available in which the toxicokinetic properties of the registered substance were investigated.

The registered substance is a liquid with a molecular weight around 192, it is slightly soluble in water (24 mg/L at 24°C) and is lipophilic (log Kow = 4.7).

The available evidence suggests that the substance is bioavailable via the oral and dermal routes. The substance is expected to be extensively metabolised and mainly excreted in urine.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

In accordance with the section 8.1.1 of Annex VIII of Regulation (EC) No 1907/2006 (REACH), the toxicokinetic profile of the substance (i.e. absorption, distribution, metabolism and elimination) was derived from the relevant available information collated in the dossier. The physical chemical characteristics of the substance, the results obtained from acute, repeated-dose, and reproductive toxicity studies on the substance were used to predict its toxicokinetic behaviour.

 

Physico-chemical properties:

The substance is a multiconstituent, having a relatively low molecular weight around 192. The substance is a slightly water soluble liquid (24 mg/L) and is lipophilic based on the octanol/water partition coefficient (Log Kow = 4.7 at 25°C). The substance has very low volatility according to its vapour pressure (0.59 Pa at 24°C).

 

Absorption:

Oral/GI absorption

The physical chemical characteristics described above suggest that the substance could be absorbed in the gastro-intestinal tract by passive diffusion. There are no ionisable groups in the parent substance so pH would not affect absorption.

These hypotheses are supported by oral adaptative systemic effects observed in the combined toxicity study with the reproduction/developmental toxicity screening test performed on the registered substance in rats by dietary administration. Animals exposed to 12000 ppm 3-cyclohexene-1-carboxaldehyde multiconstituent in the diet showed hepatocellular hypertrophy in the liver which correlated with increased organ weight. After two weeks of recovery there was no difference in the organ weight of the liver and no evidence of hepatocellular hypertrophy on histopathological examination suggesting complete reversibility of the finding. 

In light of these data, and the lack of specific information on oral absorption, the substance was assumed to be 100% bioavailable by oral route for the purposes of human health risk assessment.

 

Dermal absorption

Regarding dermal absorption, systemic absorption by the dermal route is expected to occur, although it is slightly above the Log Kow range of -1 and 4, and because of the low molecular weight (< 500 g/mol). The absence of effects in the actue toxicity study by dermal route probably indicates low toxicity rather than the absence of absorption.

In light of these data, the substance was conservatively assumed to be 100% bioavailable by dermal route for the purposes of human health risk assessment.

 

Respiratory absorption

The potential for inhalation toxicity was not evaluated in vivo.

The vapour pressure of the substance (Vp = 0.59 Pa at 24°C) indicated a low volatility and inhalability and therefore exposure by inhalation may not occur. Thus, at ambient temperature, respiratory absorption is expected to be very low under normal use and handling of the substance. However, when used as a vapour or in aerosol, the substance is expected to be directly absorbed across the respiratory tract epithelium by passive diffusion.

In light of these data, and the lack of specific information on respiratory absorption, the substance was conservatively assumed to be 100% bioavailable by inhalation for the purposes of human health risk assessment.

 

Distribution:

There is no experimental evidence to indicate distribution but the physico-chemical data suggests that wide distribution could occur. The log Kow value of 4.7 at 25°C suggests that the substance could have affinity of adipose tissues. Distribution and bioaccumulation are highly dependent on the rate of biotransformation and elimination. There is, however, no evidence of cumulative effects from the repeated dose oral toxicity study.

  

Metabolism:

Adaptative changes observed in the OECD 422 study, corresponding to hepatocellular hypertrophy, showed signs of metabolisation of the substance.  

 

Excretion:

The parent substance is slightly water-soluble therefore elimination of the unchanged form, in urine, may be limited. Biotransformation is expected and elimination of metabolites would most likely occur in urine, although elimination of conjugates in bile is possible. As the parent substance is not volatile, elimination via the lungs, in expired air is expected to be limited.

Although the registered substance has log Kow=4.7 at 25°C which is above the criterion of 4 for bioaccumulation, it is believed to be extensively and rapidly metabolised; therefore, it is considered to have low bioaccumulation potential.