Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Butyl benzoate (CAS No 136 -60 -7, EC No 205 -252 -7) is a colorless liquid with a very low water solubility (< 1mg/L), a moderate log Kow (3.30) and a moderate vapour pressure (8.5 Pa at 20°C). It has a molecular weight of 178.231 g/mole. The substance was observed to be non-sensitising to the skin and non-irritant to skin and eyes (Vasquez, 2012).

No toxicokinetic data (animal or human studies) are available on this substance. The data present in this dossier are based on physico-chemical parameters and will allow a qualitative assessment of the toxicokinetic behaviour of the test substance.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Absorption

Oral/GI absorption

Butyl benzoate is considered favorable for absorption based on its moderate molecular weight (< 500 g/mol), moderate partition coefficient (log Kow between -1 and 4). However, its low water solubility would lead to restricted dissolution of the substance into the gastrointestinal fluids and absorption through passive diffusion causing only limited absorption. It is generally assumed that the absorption along the gastrointestinal tract predominantly takes place in the small intestine.

The test substance has been tested in a combined repeated dose toxicity test with reproductive/developmental screening (according to OECD guideline 422; Martell A, 2013). Wistar Rats (5 per sex per dose) were administered 0, 250, 500, 1000 mg/kg bw/day. No mortality nor adverse effect on the body weight was observed. Differences in food consumption were observed in treated males and females but this finding was not considered to be test item related since the body weight was not affected. Any findings in hematology, clinical biochemistry, histopathology or organ weights were considered incidental therefore not treatment-related. During the microscopic tissue evaluations, three males dosed with 1000 mg/kg/day presented slight reduction of germ cells. Despite the presence of this finding, their reproductive ability was not affected, since these males produced offspring from their respective females. While the absolute number of dead pups in the high dose group was statistically significantly increased when compared to controls on day 0, the mean number of live and dead pups per litter was not significantly increased when compared to controls on day4. Therefore, this finding was considered not test item related. In the high dose dams, the total number of pups, live pups at day 0 and body weight of pups at day 4 postnatal were lower compared to the control group. These findings were not statistically significant and are not likely to be test item related. Based on the results, the test substance is not classified as reproductive toxicant. A parental, reproductive and developmental NOAEL of 1000 mg/kg bw/day was derived. 

In an acute oral toxicity study (OECD 425; Vasquez, 2012) in which 2000 and 300 mg/kg bodyweight was administered to 4 females Sprague-Dawley rats by oral gavage, the LD50 value was estimated to be greater than 2000 mg/kg.

Based on the physicochemical properties and the results of the toxicity studies, the oral absorption factor is set to 50%.

Respiratory absorption

Given the vapour pressure of 8.5 Pa, the test substance is not a highly volatile substance and the availability for inhalation as a vapour is limited.       

Generally, liquids would readily diffuse/dissolve into the mucus lining the respiratory tract. Since the water solubility of this substance is very low, the rate at which it will dissolve into the mucus limits the amount that could be absorbed directly when reaching the respiratory system. Once in the respiratory tract, and considering the lipophilic character of the substance, absorption may occur. Absorption directly across the respiratory tract epithelium by passive diffusion is favoured in view of the moderate log Kow value (-1<log Kow<4).

In an acute inhalation toxicity study in male and female Wistar rats, the LC50 was established to exceed 15.246 mg/L (Ferreira, 2012).

Based on the above considerations, the inhalation absorption factor is set to 100%.

Dermal absorption

Liquids and substances in solution are taken up more readily than dry particulates. Absorption of volatile liquids across the skin may be limited by the rate at which the liquid evaporates off the skin surface (Pryde and Payne, 1999). However, the test substance is not very volatile and penetration into the lipid rich environment of the stratum corneum is expected as it is also favoured by lipophilic character of the substance. Nevertheless, penetration from the stratum corneum into the epidermis will be limited by the very low water solubility (<1 mg/L) of the test substance. Dermal uptake is thus expected to be low to moderate based on physico-chemical characteristics.

The substance was demonstrated to be non-irritant to the skin in an in vivo study in rabbits (OECD 404) and non-irritant to eyes in an in vivo study in rabbits (OECD 405) (Vasquez, 2012).

In a Delayed Contact Hypersensitivity in male and female Hartley Guinea Pigs (Buehler Method) according to OECD Guideline 406, the test item was observed to be non-sensitising to the skin (Vasquez, 2012).

The dermal absorption factor for the test substance is set to 50%.

Distribution

The very low water solubility will limit the distribution of the test substance through the body through aqueous channels and pores. Since the substance is moderately lipophilic, the substance will only distribute into the cells to a limited extent. The toxicological studies identified no the target organs. Based on these observations it can be concluded that the test substance is not likely to distribute within the body. 

Accumulation

Based on the physicochemical properties of the substance (very low water solubility, moderate partition coefficient, low vapour pressure etc.), no accumulation is expected within the lungs, bones or stratum corneum.

Metabolism

Once absorbed, extensive hydrolysis and/or hydroxylation may occur to increase the solubility of the substance and possible oxidation followed by rapid amino acid conjugation, sulfonation or glucuronidation is expected.

Excretion

The water soluble conjugated metabolites of the test substance from Phase II biotransformation will be excreted from the systemic circulation through the urine. Most of them will have been filtered out from the blood by the kidneys, though a small amount can enter the urine directly by passive diffusion. There is also the potential for re-absorption into the systemic circulation across the tubular epithelium.