Registration Dossier

Administrative data

Description of key information

All available ORAL LD50 values
Rat: 1600, 1880, 2400-3000, 7000 mg/kg
Mouse: 2820 mg/kg
Rabbit: 118-940mg/kg, ~987mg/kg
Cat: >940mg/kg
Reliable INHALATION LC50 values
Rat: LC50(4hr)>2.66mg/l (SVC); LT50(SVC)=8hr, LC50(8hr)>SVC (3.91mg/l), LC0(3hr)>SVC (3.68mg/l)
where SVC=saturated vapour concentration.
All available DERMAL acute toxicity values:
Rabbit LD50: 1500mg/kg, 1580mg/kg (occlusive exposure)
Guinea pig LD50: 4700mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
1 880 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
1 500 mg/kg bw

Additional information

Oral route

A number of relatively old but mainly reliable studies are available to assess acute oral toxicity using various animals. Whilst the reporting of these falls short of current standards and there are some uncertainties about the purity and the experimental procedure, together they provide a consistent picture of the toxicity of this substance. The toxicological effects were mainly haemolysis and associated lesions. The data suggests that rabbits are the most sensitive species with a LD50 of around 900 mg/kg, but they are known to be very sensitive to the haemolytic effects of butoxyacetic acid, the main metabolite of the hydrolysis product 2 -butoxyethanol, and therefore not representative of the acute toxicity in humans, who are very resistance to haemolysis induced by the metabolites of the substance . The LD50 in the preferred species of rat is significantly higher (lowest reliable values 1880mg/kg and 2820mg/kg respectively.) Data for mice suggests an LD50 of around 3000mg/kg. A single value of >940mg/kg is available for the cat but this limit value is of little use for classification purposes. This pattern of results is consistent with data for the surrogate parent glycol ether 2 -butoxyethanol, where the rabbit is again found to be the most sensitive species from which the predicted LD50 values would be 1300 -3500mg/kg for rats and 1400 -2700mg/kg for mice. The rat and mouse are also sensitive to haemolysis, but since there is no data in a haemolysis resistant species such as the guinea pig, the lowest LD50 from the preferred species (rat) should be use as a conservative indicator of acute toxicity in humans.

Inhalation route

A number of study results are available across multiple species but all studies are relatively old and those in species other than rats are deemed unreliable. However, at least two of these are judged reliable and all of the other studies provide data which is consistent with these one or two and lead to the conclusion that the LC50 for this substance cannot be achieved under ambient conditions due to its low vapour pressure and relatively low toxicity. Studies using vapour concentrations between 2.66 -3.91mg/l or 81 >100% of the theoretical saturated vapour concentration) consistently showed, directly or indirectly, no lethality for exposures of 4 hours. Other adverse effects were seen, particularly haemoglobinuria in rats, which is consistent with the known toxic effects of the main metabolite (2 -butoxyethanol) of this substance.

Dermal route

There are two studies available for 2 -butoxyethyl acetate. Both were performed with rabbits showed similar LD50 values of around 1500mg/kg. The main toxicity symptoms were haemolysis and associated lesions. A much higher value is available for guinea pigs which confirms that this species is resistant to the toxic effects of this substance (actually, in practice, the metabolite 2 -butoxyacetic acid.) Since the rabbit has been shown above to be the most sensistive species, it is likely that for the dermal route the rabbit again represents the 'worse case' species. It would be preferable to use the rat for consistency with the oral route but no data is available in this species.

Justification for classification or non-classification

Oral route

The preferred species for classification is the rat. Data is available for other species, rabbit and mouse, but the reasons for not selecting these species for the key parameter are described in the section above. The lowest obtained LD50 data from rats indicates classification is required (just) although some values obtained suggest classification may not be required.

Inhalation route

The LC50 for this substance cannot be reached under ambient conditions due to its low volatility. This has been demonstrated in multiple studies across multiple species which when exposed to saturated vapour concentrations for 4 hours have not produced any lethality in test animals. A classification for acute toxicity by the inhalation route is not therefore warranted. It should be noted that the currently listed harmonised classification does include classification for this route and, whilst it was agreed as not appropriate in the EU risk assessment and confirmed at the EU Classification and Labelling Working Group, this decision was never implemented under directive 67/548 before it was repealed by regulation 1272/2008.

Dermal route

The LD50 for exposure under occluded conditions to 2 -butoxyethyl acetate has been shown in two studies to be around 1500mg/kg. This would indicate that classification for acute toxicity by the dermal route is required under both the EU DSD (harmful) and the EU GHS implementation (as category 4).

It should be noted that severe haemolytic anaemia was observed in the rabbit and this effect is likely to be a significant if not key contributor to death. This is an effect to which humans are notably resistant, as are guinea pigs, which could therefore be considered a more representative species. It is likely therefore that the harmful classifications above are likely to exaggerate the actual hazard to humans.