Assessment of the relative hazard involved with airborne irritants with additional hepatotoxic or nephrotoxic properties in mice.
This paper deals with the conversion of the hepatotoxicity of 1,2-dichlorobenzene (DCB), the nephrotoxicity of hexachloro-1,3-butadiene (HCBD) and the respiratory effects of these two toxicants into quantal data. It aims to provide some useful information on the best strategy used for safety evaluation. A reflex bradypnea indicative of irritation of the nasal cavities of mice occurred during a 15-min oronasal exposure to each chemical. A reduction in the development of staining for liver glucose-6-phosphatase (G6-phosphatase) and an increase in the number of damaged tubules in cryostat kidney sections stained for alkaline phosphatase were the measure of toxicity in mice subjected to a whole-body 4-h exposure to DCB and HCBD vapours, respectively. The immediate irritant responses, as well as the delayed liver and kidney responses, were measured at the peak of the chemical's action. These maximum responses were then used to establish the relationships of exposure level effects and also the median active levels of exposure (MALs). The DCB and HCBD MALs responsible for a 50% decrease in the respiratory rate of mice (RD50) were 181 and 211 ppm, respectively. The MAL required for eliciting a 50% decrease in G6-phosphatase staining intensity in DCB-exposed mice was 598 ppm and that associated with 50% of damaged tubules in HCBD-exposed mice was 7.2 ppm. On the basis of these quantitative data, potency ratios indicated that irritation and kidney injury are the primary manifestations of toxicity associated with short-term exposure to DCB and HCBD, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
De Ceaurriz
J
J
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Gagnaire
F
F
Ban
M
M
Bonnet
P
P
D000393:Air Pollutants / Q000633:toxicity*; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D002070:Butadienes / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology*; D002722:Chlorobenzenes / Q000633:toxicity; D005952:Glucose-6-Phosphatase / Q000032:analysis; D006651:Histocytochemistry; D007509:Irritants / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D051379:Mice; D012137:Respiratory System / Q000187:drug effects
D000393:Air Pollutants; D002070:Butadienes; D002722:Chlorobenzenes; D007509:Irritants; C004726:2-dichlorobenzene; C001335:hexachlorobutadiene; D000469:Alkaline Phosphatase; D005952:Glucose-6-Phosphatase