Methyl salicylate

Endpoint summary

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.