Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

 The available evidence suggests that the substance is bioavailable via the oral and dermal route. Systemic absorption of this substance via inhalation route is expected but to a limited extent. The substance is expected to be 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 or on related substances (see Section 13 for read-across justification) were used to predict its toxicokinetic behaviour.

 

Physical-chemical properties:

The substance is a reaction mass of two isomers cis/trans), having a relatively low molecular weight of 228.29 g/mol. The substance is water soluble liquid (1.28 g/L) and is moderately lipophilic based on the octanol/water partition coefficient (Log Kow = 2.61). The substance has low volatility according to its vapour pressure (0.2 Pa at 25°C).

 

Absorption:

Oral/GI absorption

The physical chemical characteristics described above suggest that the substance is absorbed in the gastro-intestinal tract by passive diffusion. Water-soluble substances will readily dissolve into the gastrointestinal fluids. Absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. The absence of effects in the toxicity studies probably indicates low toxicity rather than the absence of absorption. There are no ionisable groups in the parent substance so pH would not affect absorption.

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 be moderate to high based on the Log Kow and the water solubility values. The absence of effects in the toxicity studies 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 = 0.2 Pa at 25°C) indicated a low volatility and inhalability and therefore no exposure by inhalation is anticipated. Thus, at ambient temperature, no respiratory absorption is expected under normal use and handling of the substance.

However, when used as a vapour 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. However, the log Kow value of 2.61 suggests that the substance would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous. 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. The substance is not a contact sensitizer so it may not become bound to proteins.

  

Metabolism:

In vitro Ames and chromosome aberration tests showed some evidence of attenuation of cytotoxicity in the presence of S9 which might indicate biotransformation by microsomal enzymes. The most likely route of biotransformation involves hydrolysis of the ester groups by carboxylic acid esterase to produce the corresponding acid and alcohol. Subsequent oxidative metabolism and conjugation reactions would also be expected.

 

 

Excretion:

The studies conducted provide no information regarding route of excretion. The parent substance is moderately water-soluble so some elimination of the unchanged form, in urine, might be possible. Biotransformation is expected, however, and elimination of metabolites would most likely occur in urine, although elimination of conjugates in bile is possible. The parent substance is not sufficiently volatile for any appreciable elimination via the lungs, in expired air.