Registration Dossier

Administrative data

Description of key information

ORAL LD50 values:

Rat, male: 2460mg/kg

Rat, male: 2257mg/kg (fasted), 3930mg/kg (non-fasted)

Rat, male: 3250mg/kg

Rat, female: 3400mg/kg

Guinea pig, male/female; 950mg/kg

INHALATION LC50 values (all rat):

>20mg/l (male and female)

>16mg/l.  NOEC=0.95mg/l (male)

~16mg/l (male)

DERMAL LD50 (all male rabbit)

3930mg/kg

1340ml/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
950 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
16 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
1 340 mg/kg bw

Additional information

A number of oral acute toxicity studies are available. Some are quite old but at least one study in rats is sufficiently reliable for the purposes of hazard assessment. A number of studies are available in rats (multiple species), both male and female, both fasted and non-fasted animals. Values obtained are reasonably consistent, ranging from 2257mg/kg in fasted animals to 3930 in non-fasted animals. This is the species normally used for acute toxicity classification by the oral route. Lower values are available for the guinea pig and rabbit. The sole value for the rabbit could not be judged for its reliablility, but the value for the guinea pig of 950mg/kg (male and female) was judged reliable based on the detail provided in the publication.

In a study designed to assess interlaboratory variation of the OECD acute inhalation toxicity study, a number of different rat strains were exposed to 2 -methoxyethanol vapour in the concentration range of 25 -33mg/l (average 29mg/l). No deaths resulted when the animals were exposed to this concentration for 1 -3 hours. From these results it was possible to predict that the LC50 is likely to be greater than 20mg/l. In another study designed to assess testes effects following acute exposure, male rats were exposed to a number of concentrations of methoxyethanol in the range 150ppm up to saturated vapour pressure for a period of 4 hours. No deaths were observed at any concentration. However, the study did note adverse effects on the testes of animals exposed to 625ppm and above of methoxyethanol, producing a NOAEC of 300ppm (0.95mg/l). The study did not provide a true LC50 and as such the results are only of partial use for classification and labeling purposes, but they can be used to derive a NOAEC for risk assessment purposes with appropriate safety factors. It can also be concluded that the LC50 is greater than 5000ppm (15.8mg/l). In an acute toxicity range finder study by the inhalation route, male rats were exposed to a number of concentrations of methoxyethanol for a period of 4 hours. All animals tolerated and exposure of 12.4mg/l but 60% mortality was seen at 17.8mg/l, suggesting that the LC50 fell within this range.

In an acute dermal toxicity study, male rabbits were exposed to 2 -methoxyethanol. The LD50 was estabilished as 3939mg/kg. Sub-lethal effects were seen at lower doses including anorexia, slight depression, cyanosis, ataxia, soft faeces, and at higher doses salivation, nasal discharge, iritis, significant depression, llaboured breathing, and prostration. A second study in rabbits produced a much lower LD50 of 1340ml/kg. Only basic details are reported in the study but it is considered that the result cannot be excluded from the overall evaluation of the acute dermal toxicity of this substance.

It appears that the rabbit and guinea pig are more sensitive than the rat and mouse.

Justification for classification or non-classification

For the oral route, based on the results of the two species normally used, the substance does not warrant classification for acute toxicity in accordance with the current EU guidelines. However, the result from the guinea pig cannot be completely excluded which suggests that classification as harmful is appropriate.

For the inhalation route, methoxyethanol does not appear to be particularly toxic, with the majority of studies (in rats only) indicating that classification is not required. However, one study indicated an LC50 of approximately 16mg/l. Based on this result, methoxyethanol falls marginally within the category where classification as harmful by the inhalation route is required.

Limited and mixed results are currently available for the dermal route and in only one species (rabbit). However, the lowest reliable value available indicates that classification as harmful is warranted.