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Administrative data

Description of key information

A number of studies have been published on the acute toxicity of methyl salicylate by the oral, dermal and inhalation routes in several species. For oral toxicity, a pre-GLP study in rats (Rel. 2) by Jenner (1964) has been chosen as key study. The oral LD50 values from other sources, most of which are secondary references (Rel. 4), are consistent with the key study and are submitted on a weight of evidence basis.

No single reliable study is available for dermal toxicity, however data from two secondary references (Rel. 4) are submitted on a weight of evidence basis to fulfil this endpoint.

No fully reliable acute toxicity study is available for inhalation toxicity. This endpoint is fulfilled on a weight of evidence basis, using primarily a sub-acute inhalation study of Rel. 2 (Gage, 1970) reported in section 7.5.3. A secondary reference to three acute studies of unknown duration (Rumyantsev, 1992, Rel. 4) and a limited report (Bio-Fax, 1971, Rel. 3) of a one-hour inhalation study on the primary metabolite SA also support the conclusion that MeS is not hazardous by inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
887 mg/kg bw

Additional information

Oral Toxicity

The key study (Jenner, 1964) reports oral LD50 887 mg/kg. Other reported values range from 580 to 2800 mg/kg for rat, mouse, rabbit, guinea pig and dog, as summarised in the table below. These LD50 values indicate that methyl salicylate is of moderate toxicity by the oral route.

Acute Oral Toxicity Studies on methyl salicylate

Species

LD50 (mg/kg)

Reference

Rel.

Rat

887

Jenner, 1964

2

Rat

2820

RIFM, 1982

2

Rat

1220 (m) / 1060 (f)

Rumyantsev, 1992

4

Rat

1250

Giroux, 1954

4

Mouse

1390

Ohsumi, 1984

4

Mouse

580

Rumyantsev, 1992

4

Mouse

1100

Davison, 1961

3

Rabbit

1300

Castagnou, 1952

4

Rabbit

2800

Fassett, 1963

4

Rabbit

2800

Rumyantsev, 1992

4

Guinea pig

700

Rumyantsev, 1992

4

Guinea pig

1060

Jenner, 1964

2

Dog

2100

Bisesi, 1994

4

 

 Dermal Toxicity

Two of the three dermal toxicity studies (Bisesi, 1994; Moreno, 1973) report a dermal LD50 value >2000 mg/kg in rat and rabbit as summarised in the table below. The data from these studies have been used to assess this endpoint. By weight of evidence, the dermal toxicity of MeS is considered to be low.

 Acute Dermal Toxicity Studies on methyl salicylate 

Species

LD50 (mg/kg)

Reference

Rel.

Rat

> 2500

Bisesi, 1994

4

Rabbit

> 5000

Moreno, 1973

4

Guinea pig

700

Bisesi, 1994

4

 

Inhalation Toxicity

  Three acute inhalation toxicity studies on MeS (Rumyantsev et al, 1992) report no mortality at concentrations up to 400 mg/m3in rat and mouse as summarised in the table below, however no exposure period was reported. A 1-hour inhalation study (Bio-Fax, 1971) on SA, the principal metabolite, also indicates low acute toxicity. Since these studies are not sufficient to conclude that no classification is required for acute inhalation toxicity, the key study chosen for this endpoint is sub-acute study (Gage, 1970), where rats were exposed to MeS at an almost saturated concentration of 700 mg/m3for 7 hours per day for 5 days per week for 4 weeks. No adverse effects were reported and it is concluded that MeS is of low toxicity by inhalation.

Inhalation Toxicity Studies on methyl salicylate

Species

LC50 (mg/m3)

Duration

Reference

Rel.

Rat

> 400

Unknown

Rumyantsev, 1992

4

Rat

> 114

Unknown

Rumyantsev, 1992

4

Mouse

> 400

Unknown

Rumyantsev, 1992

4

Rat (SA)

> 900

1h

BioFax, 1971

3

Rat

> 700 (almost saturated atmosphere)

7h/d, 5d/wk/4-week

Gage, 1970

2

 

Justification for classification or non-classification

Acute Oral Toxicity:

Methyl salicylate oral LD50 (rat): 887 mg/kg

The limit values for classification of a substance as harmful on acute exposure by the oral route are:

EU DSD (Xn, R22):    200-2000mg/kg

UN/EU GHS (Acute toxicity Cat. 4):   300-2000mg/kg

Methyl salicylate should therefore be classified as Harmful for acute oral toxicity:

EU DSD:       Xn, R22

UN/EU GHS  Acute toxicity Cat. 4, H302

 

Acute Dermal Toxicity:

Methyl salicylate dermal LD50 (rat): >2000 mg/kg

The limit values for classification of a substance as harmful on acute exposure by the dermal route are:

EU DSD (Xn, R22):    400-2000mg/kg

UN/EU GHS (Acute toxicity Cat. 4):   1000-2000 mg/kg

Methyl salicylate should therefore not be classified for acute dermal toxicity according to the criteria of EU DSD or EU GHS

 

Acute Inhalation Toxicity:

The absence of any adverse effects from repeated exposure to MeS vapour at 0.7 mg/l (almost saturated atmosphere) for 7 hours per day 5 days per week for 4 weeks supports a conclusion that classification for acute inhalation toxicity is not required according to the criteria of EU DSD or UN/EU GHS.