An introductry presentation on Toxicology by Mike Slater of Diamond Environmental Ltd.

1. Mike Slater Diamond Environmental Ltd

2. "All substances are poisons ; there is none which is not a poison. The right dose differentiates a poison from a remedy"

5. Inhalation Skin contact Ingestion

13. V t = terminal velocity g = acceleration due to gravity d = diameter of particle p p = density of particle p m = density of medium µ = viscosity of medium

30. Metabolites - Some Examples Substance Metabolite Benzene Phenol Dichloromethane Carbon monoxide N-hexane 2, 5 hexanedione Methanol Formaldehyde Styrene Mandelic acid Phenylglyoxylic acid Toluene Hippuric acid o- cresol Trichloroethylene Trichloroacetic acid Trichloroethanol Xylene Methyl-hippuric acid

47. Threshold Dose

69. Causes local inflammation of tissue

70. Destroys tissue

71. Depresses Central Nervous System Causes dizziness, nausea, drowsiness

72. Causes an allergic reaction in susceptible people

74. Sensitisers – CHIP Classifications R42 May cause sensitisation by inhalation R43 May cause sensitisation by skin contact

76. Source: http://www.hse.gov.uk/statistics/causdis/asthma.htm

77. Source: http://www.hse.gov.uk/statistics/causdis/asthma.htm

80. Stops body functioning normally

81. Classification depends on dose required to cause effect

90. Carcinogens - CHIP Classification Category 1 Substances known to be carcinogenic in humans R45 May cause cancer Category 2 Evidence of cancer from animal studies R45 May cause cancer Category 3 Suspect carcinogens R40 Limited evidence of a carcinogenic effect

91. Carcinogens – Some Examples Category 1 Arsenic Asbestos Benzene Benzidine Vinyl chloride monomer R45 May cause cancer Category 2 Beryllium Cadmium oxide Strontium chromate Trichloroethylene R45 May cause cancer Category 3 Chloroform Formaldehyde Hydroquinnone Lead chromate R40 Limited evidence of a carcinogenic effect

96. Mutagens - CHIP Classification Category 1 Substances known to be mutagenic in humans R46 May heritable genetic damage Category 2 Evidence from animal or in-vitro studies R46 May heritable genetic damage Category 3 Suspected mutagens R68 Possible risk of irreversible effects

97. Mutagens - CHIP Classification Category 1 R46 May heritable genetic damage Category 2 Butadiene Benzene Sodium chromate R46 May heritable genetic damage Category 3 Aniline Trichloroethylene Vaadium pentoxide R68 Possible risk of irreversible effects

100. Interactions - Independent No interaction

101. Interactions - Additive The combined effect is equal to the individual sum of the effects Example – Narcotics, usually same target organ same mechanism

102. Interactions - Synergistic Combined effect is greater than sum of individuals e.g. Ethanol & Carbon tetrachloride

103. Asbestos and lung cancer (Lung cancer death rates per 100 000 person years) Asbestos worker Smoker Death rate Mortality rate No No 11.3 1 Yes No 58.4 X 5 No Yes 122.8 X 11 Yes Yes 601.6 X 53

104. Interactions - Potentiation Substance increases the effect of a hazardous substance e.g. Isopropanol & carbon tetrachloride, barbiturates and solvents

105. Interactions - Antagonistic Substance reduces effect of another substance Cd & Zn – less kidney damage

110. Plot the dose-response curve for the following data dose No. of deaths Group size % deaths 5 0 20 0 10 0 20 0 25 3 20 15 50 7 20 35 100 15 20 75 250 19 20 95 500 20 20 100 1000 20 20 100

111. Dose response curve for previous data

114. NOAEL LD50

116. Hodge-Sterner Table LD50 Toxicity degree Probable lethal dose <1.0 mg/kg Dangerously Toxic A taste 1-50 mg/kg Seriously Toxic A teaspoon 50-500 mg/kg Highly Toxic An ounce 0.5- 5gm/kg Moderately Toxic A pint 5- 15gm/kg Slightly Toxic A quart >15gm/kg Extremely low Toxicity More than a quart

121. Toxicological studies are normally carried out over a short timescale.

122. What are the implications of this?