Priority Existing Chemical

i.5Summary

Studies investigating the biotransformation of MMT in vitro indicate the liver is the predominant site of MMT metabolism, followed by the lung, kidney and brain. As the metabolism of MMT in lung and liver microsomes in vitro is inhibited by carbon monoxide and N-decylimidazole, it is likely the cytochrome P-450 monoxygenase enzyme is responsible for the metabolism of MMT in rats. MMT and its metabolites are predominantly excreted in the urine and faeces of rats. The most abundant MMT metabolite was determined to be CMT followed by HMT.

j)Toxicity of MMT

j.1Acute toxicity

The major acute toxic effects of MMT include damage to the lungs by all routes, kidney, liver and spleen effects, tremors, convulsions, dyspnea and weakness.

Table 12. Summary of MMT acute lethality studies

Route	Species	Result	Reference
Inhalation	Rat	LC50 (4hr) > 2 mg/m3	Moore et al., 1975a
	Rat	LC50 (1hr) = 247 mg/m3	Ethyl Corporation, 1976h; Hinderer, 1979
	Rat	LC50 (4hr) = 76 mg/m3	Ethyl Corporation, 1976h; Hinderer, 1979
	Rat	LC50 (1hr) > 19.8 g/m3 (approx.)*	Ethyl Corporation, 1976a
	Rat	LC50 (1hr) = 220 mg/m3	Witherup et al, Unknown date b
Oral	Rat (f)a	LD50 = 22.9 mg/kg bw	Witherup and Larson, 1965
	Rat (f)b	LD50 = 16.8 mg/kg bw	Witherup and Larson, 1965
	Rat (m)a	LD50 = 38.5 mg/kg bw	Witherup and Larson, 1965
	Rat (m)b	LD50 = 23.7 mg/kg bw	Witherup and Larson, 1965
	Rat (m)	LD50 = 175 mg/kg bw**	Witherup and Roell, 1965
	Rat (f)	LD50 = 89 mg/kg bw**	Witherup and Roell, 1965
	Rat	LD50 = 58 mg/kg bw	Hysell et al., 1974; Moore et al., 1975a
	Rat	LD50 = 58 mg/kg bw	Ethyl Corporation, 1975a; Hinderer, 1979
	Rat	LD50 = 175 mg/kg bw*	Ethyl Corporation, 1976b
	Rat	LD50 = 50 mg/kg bw	Hanzlik et al., 1980a
	Rata	LD50 = 23-176 mg/kg bw	Witherup et al., Unknown date b
	Ratb	LD50 = 9->80 mg/kg bw	Witherup et al., Unknown date b
	Mouse	LD50 = 230 mg/kg bw	Ethyl Corporation, 1977c; Hinderer, 1979
	Mouse (f)	LD50 = 60 mg/kg bw	Majima, 1985

Table 12. Summary of MMT acute lethality studies (cont.)
Route	Species	Result	Reference
	Mouse (m)	LD50 = 34 mg/kg bw	Majima, 1985
	Mouse	LD50 = 352 mg/kg bw	Witherup et al., Unknown date b
	Guinea pig (f)	LD50 = 905 mg/kg bw	Witherup et al., Unknown date b
	Rabbit (f)	LD50 = 95 mg/kg bw	Witherup et al., Unknown date b
Dermal	Rabbit	LD50 (24 hrs) = 1350 mg/kg bw**	Witherup and Roell, 1965
	Rabbit	LD50 (24 hrs) = 140 mg/kg bw	Ethyl Corporation, 1975b; Hinderer, 1979
	Rabbit	LD50 (24 hrs) > 2000 mg/kg bw*	Ethyl Corporation, 1976c
	Rabbit	LD50 (24 hrs) = 196.7 mg/kg bw	Ethyl Corporation, 1976e; Hinderer, 1979
	Rabbit	LD50 (24 hrs) = 420 mg/kg bw	Ethyl Corporation, 1976f; Hinderer, 1979
	Rabbit	LD50 (24 hrs) = 795 mg/kg bw	Ethyl Corporation, 1976g; Hinderer, 1979
	Rabbita	LD50 (6 hrs) = 665 mg/kg bw	Witherup et al., Unknown date b
	Rabbitb	LD50 (24 hrs) = 135 mg/kg bw	Witherup et al., Unknown date b
Intraperitoneal	Rat	LD50 = 23 mg/kg bw	Hanzlik et al., 1980a
	Rat	LD50 = 6 mg/kg bw	Hakkinen & Haschek, 1982
	Rat	LD50 = 12.1 mg/kg bw	Cox et al., 1987
	Rat	LD50 = 4 mg/kg bw	Verschoyle et al., 1993
	Mouse	LD50 = 138 mg/kg bw	Hakkinen & Haschek, 1982
	Mousec	LD50 = 152 mg/kg bw	Fishman et al., 1987
	Moused	LD50 = 999 mg/kg bw	Fishman et al., 1987
	Hamster	LD50 = 270 mg/kg bw	Hakkinen & Haschek, 1982
Subcutaneous	Rat	LD50 > 10 mg/kg bw	Clay & Morris, 1989
Intravenous	Rabbit	LD50 = 6.6 mg/kg bw	Witherup et al., Unknown date b

b = kerosene vehicle e = Wesson oil vehicle

c = propylene glycol vehicle f = female only

d = corn oil vehicle

* = product tested is 62% MMT in petroleum distillate

** = product tested is 10% MMT in kerosene

The LC50 for the rat ranges from 220 to 247 mg/m³ for a 1 hour exposure and >2 to 76 mg/m³ for a 4 hour exposure. The LC50 for 62% MMT in petroleum distillate (1 hour exposure) is >19.8 g/m³.

Dermal (24 h) LD50 values for undiluted MMT in the rabbit range from 140 to 795 mg/kg bw. The dermal (24 h) LD50 for 10% MMT in kerosene is 1350 mg/kg bw and for 62% MMT in petroleum distillate is > 2000 mg/kg bw.