Residual Solvents

USP <467>, Residual Solvents

Residual solvents assessed in USP <467> were evaluated by gas chromatography for their possible risk to human health and placed into one of three classes as follows:

Class 1 Residual Solvents: Solvents to be avoided, known human carcinogens, strongly suspected human carcinogens, and environmental hazards

Solvent	Concentration Limit (ppm)	Concern
Benzene	2	Carcinogen
Carbon tetrachloride	4	Toxic and environmental hazard
1,2-Dichloroethane	5	Toxic
1,1-Dichloroethene	8	Toxic
1,1,1-Trichloroethane	1500	Environmental hazard

Class 2 Residual Solvents: Solvents to be limited, nongenotoxic animal carcinogens or possible causative agents of other irreversible toxicity, such as neurotoxicity or teratogenicity, and solvents suspected of other significant but reversible toxicities

Solvent	PDE (mg/day)	Concentration Limit (ppm)
Acetonitrile	4.1	410
Chlorobenzene	3.6	360
Chloroform	0.6	60
Cyclohexane	38.8	3880
1,2-Dichloroethene	18.7	1870
1,2-Dimethoxyethane	1.0	100
N,N-Dimethylacetamide	10.9	1090
N,N-Dimethylformamide	8.8	880
1,4-Dioxane	3.8	380
2-Ethoxyethanol	1.6	160
Ethylene glycol	6.2	620
Formamide	2.2	220
Hexane	2.9	290
Methanol	30.0	3000
2-Methoxyethanol	0.5	50
Methylbutylketone	0.5	50
Methylcyclohexane	11.8	1180
Methylene chloride	6.0	600
N-Methylpyrrolidone	5.3	530
Nitromethane	0.5	50
Pyridine	2.0	200
Sulfolane	1.6	160
Tetrahydrofuran	7.2	720
Tetralin	1.0	100
Toluene	8.9	890
Trichloroethylene	0.8	80
Xylene	21.7	2170
* Usually 60% m-xylene, 14% p-xylene, 9% o-xylene with 17% ethyl benzene****

Class 3 Residual Solvents: Solvents with low toxic potential. No health-based exposure limit is needed.

Acetic acid	Heptane
Acetone	Isobutyl acetate
Anisole	Isopropyl acetate
1-Butanol	Methyl acetate
2-Butanol	3-Methyl-1-butanol
Butyl acetate	Methylethylketone
tert-Butylmethyl ether	Methylisobutylketone
Cumene	2-Methyl-l-propanol
Dimethyl sulfoxide	Pentane
Ethanol	1-Pentanol
Ethyl acetate	1-Propanol
Ethyl ether	2-Propanol
Ethyl formate	Propyl acetate
Formic acid