Thursday, November 12, 2009

MIMER Notes, November 9, 2009

Medawar Institute for Medical and Environmental Research (MIMER)

Acute and chronic toxicities of arsenic in selected mammals including man: some notes on doses and vulnerabilities

By Sergio Ulhoa Dani, November 9, 2009.

Acute mortality

Different mammal species have different susceptibilities to arsenic acute toxicity, as assessed by LD50 and LC50 [1-12]. The LD50 defines the oral lethal dose that will kill 50% of the tested animals that eat the substance; and the LC50 defines the inhaled lethal concentration that will kill 50% of the tested animals breathing the substance.

A sequence of increased arsenic vulnerability as assessed by LD50 (LC50 for cat) is as follows: mouse (Ca or Pb arsenate p.o., 145-794 mg/kg) < rat (Ca or Pb arsenate p.o., 20-763 mg/g) < cat (AsCl3 gas, 100-200 mg/m3) < rabbit (Ca or Pb arsenate p.o., 50-75 mg/kg) < dog (Ca or Pb arsenate p.o., 38 mg/kg) < human (arsenate p.o., 1 mg/kg).

The vulnerability sequence as derived LC50 values (30 min exposure time) would be as follows [13]: mouse (73-209 mg As/m3) < rat (5.3-534 mg As/m3) < rabbit (8.8-13 mg As/m3) < dog (10 mg As/m3) < cat (5.2-7.8 mg As/m3) < human (estimated 5 mg As/m3).

Chronic morbidity and mortality

 Dose-response relationships have been well documented for arsenic in drinking water and several of the leading causes of morbidity and mortality, starting from low-to-moderate As levels [6,14-22].

There are national and international guidelines which can help you define levels of As in water, but safety standards tend to be kept at minimal levels possible, largely based on analytical capacity.

 As a “rule of thumb” or a “digit rule” (not as a safety rule) one could arbitrarily stage As levels in water as follows: a low level would be a one-digit figure, e.g. 1 part of As per billion parts of water (1 ppb); moderate level would be a two-digit figure (e.g., 10 ppb); high level would be a three-digit figure (100 ppb and above). Caveats: (i) As levels may not correlate linearly with health effects; (ii) high levels of As in drinking water result in the highest known increases in mortality attributable to any environmental exposure [19,21,22] and (iii) there is no such thing as a “safe dose” of a carcinogenic substance like As.

Arsenic can also be absorbed by inhalation. NIOSH recommends as part of its occupational carcinogen policy that the "most protective" respirators be worn for inorganic arsenic compounds at concentrations above 0.002 mg As/m3 [10]. Note that this recommendation is given for acute occupational exposure and that chronic exposure may require much lower As concentrations to affect human health. References:

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