Archives of Toxicology

, Volume 62, Issue 2–3, pp 123–132 | Cite as

The repeated dose toxicity of a zinc oxide/hexachloroethane smoke

  • T. C. Marrs
  • H. F. Colgrave
  • J. A. G. Edginton
  • R. F. R. Brown
  • N. L. Cross
Original Investigations


Mice, rats and guinea pigs were exposed to the smoke produced by ignition of a zinc oxide/hexachloroethane pyrotechnic composition, 1 h/day, 5 days/week, at three different dose levels, together with controls. The animals received 100 exposures except for the high dose guinea pigs, which underwent 15 exposures, because of high death rate during the first few days of exposure. The test material had very little effect on weight gain, but there was a high rate of early deaths in the top dose of mice. A variety of incidental findings was seen in both decedents and survivors, but organ specific toxicity was, with one exception, confined to the respiratory tract. The most important of these findings was a statistically significant increase in the frequency of alveologenic carcinoma in the high dose group mice (p<0.01) and a statistically significant trend in the prevalence of the same tumour over all dose groups and the controls. A variety of inflammatory changes was seen in the lungs of all species and some appeared to be treatment-related. Fatty change in the mouse liver was more common in the middle and high dose groups than the controls. The aetiology of the tumour incidence is discussed and it is pointed out that hexachloroethane and zinc, as well as carbon tetrachloride, which may be present in the smoke, may be animal carcinogens in appropriate circumstances. Carbon tetrachloride is a known human carcinogen.

Key words

Zinc oxide Hexachloroethane Repeated dose toxicity Mice Rats Guinea pigs 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. American Conference of Governmental Industrial Hygienists (1985–1986) TLVs threshold limit values and biological exposure limits for 1985–1986. ACGIH, Cincinnati, OhioGoogle Scholar
  2. Andrew W, Pruett D (1957) Senile changes in th kidney of Wistar institute rats. Am J Anat 100: 51–80Google Scholar
  3. Ardran GM (1950) The pulmonary effects of toxic gases and smokes an experimental radiographic investigation. Br J Radiol 23: 107–115Google Scholar
  4. Baganz von H, Perkow W, Lim GT, Meyer F (1961) Zur Toxicität von alkoxylierten und chlorierten Äthänen und Äthenen. Arzneimittel Forsch 11: 902–904Google Scholar
  5. Ballantyne B, Clifford WE (1978) Short-term inhalation toxicology of cinnamic acid smoke. J Combust Toxicol 5: 253–270Google Scholar
  6. Blair A, Decoufle P, Grauman D (1979) Causes of death among laundry and dry cleaning workers. Am J Publ Hlth 69: 508–511Google Scholar
  7. Burton FG, Clark ML, Miller RA, Schirmer RE (1982) Generation and characterization of red phosphorus smoke aerosols for inhalation exposure of laboratory animals. Am Ind Hyg Assoc J 43: 767–772Google Scholar
  8. Casey HW, Ayers KM, Robinson FR (1979) The urinary system. In: Bernischke K, Garner FM, Jones TC (eds) Pathology of laboratory animals, Vol 1. Springer-Verlag, New York, pp 116–173Google Scholar
  9. Conover WK (1980) Non-parametric statistics, 2nd Ed. John Wiley and Sons, New York, p 344Google Scholar
  10. Cullumbine H (1957) The toxicity of screening smokes. J R Army Med Coll 103: 119–122Google Scholar
  11. Deknudt G, Deminatti M (1978) Chromosome studies in human lymphocytes after in vitro exposure to metal salts. Toxicology 10: 67–75Google Scholar
  12. Dept of Health, Education and Welfare, National Cancer Institute (1978) Bioassay of hexachloroethane for possible carcinogenicity: technical report series 68, US Department of Health Education and Welfare Publication No NIH78-1318, Washington DCGoogle Scholar
  13. Drury RAB, Wallington EA (1969) Carleton's histological technique, 4th Edition. Oxford University Press, New York, p 225Google Scholar
  14. Elinder C-G (1986) Zinc. In: Friberg L, Nordberg GF, Vouk VB, Kessler E (eds) Handbook on the toxicology of metals, Volume 2. Elsevier, Amsterdam, pp 664–679Google Scholar
  15. FAInspSan (1982) Erste Hilfe und ärztliche Sofortmaßnahmen bei Vergiftungen durch Zinkchlorid-Nebelmittel. Report No A 42.06 (1/82), Bundesministerium der VerteidigungGoogle Scholar
  16. Fischer H (1974) Morphologie der Zinknebelvergiftung der Lunge. Pneumologie 150: 171–172Google Scholar
  17. Glaister JR (1986) Principles of toxicological pathology. Taylor and Francis, London, pp 198–199Google Scholar
  18. Grady HG, Stewart HL (1940) Histogenesis of induced pulmonary tumors in strain A mice. Am J Pathol 16: 417–432Google Scholar
  19. Grasso P, Crampton RF, Hooson J (1977) The mouse and carcinogenicity testing. British Industrial Biological Research Association, Carshalton, Surrey, June, 1977Google Scholar
  20. Greaves P, Faccini JM (1984) Rat histopathology. Elsevier, Amsterdam, p 144Google Scholar
  21. Helm von KU, Renovanz H-D, Schmahl K, von Clarmann M (1971) Die Zinknebelvergiftung und ihre Behandlung II Symptomlogie und Verlauf der Vergiftungen. Wehrmed Monatsschr 15: 203–217Google Scholar
  22. Helm von KU, Renovanz HD (1975) Clinical-pharmacological contribution to the intensive-care therapy of zinc chloride smoke poisoning with glucocorticoids. Therapiewoche 41: 5914–5920Google Scholar
  23. Henschler D (1987). Mechanisms of genotoxicity of chlorinated aliphatic hydrocarbons. In: de Matteis F, Lock E (eds) Selectivity and molecular mechanisms of toxicity. Macmillan Press, Basingstoke, pp 153–181Google Scholar
  24. Hoar R (1976) Toxicology and teratology. In: Wagner JE, Manning PJ (eds) The biology of the guinea pig. Academic Press, New York, pp 269–280Google Scholar
  25. IARC (1979a) Monographs on the evaluation of the carcinogenic risk of chemicals to humans, volume 20, some halogenated hydrocarbons. International Agency for Research on Cancer, Lyons, pp 467–476Google Scholar
  26. IARC (1979b) Monographs on the evaluation of the carcinogenic risk of chemicals to humans, volume 20. Some halogenated hydrocarbons. International Agency for Research on Cancer. Lyons, pp 371–381Google Scholar
  27. Jarvis A (1970) The combustion reactions of a pyrotechnic white smoke composition. Combustion and Flame 14: 314–320Google Scholar
  28. Johnson FA, Stonehill RB (1961) Chemical pneumonitis from inhalation of zinc chloride. Dis Chest 40: 619–624Google Scholar
  29. JSP 312 (1987) Medical Manual of defence against chemical agents. UK Ministry of Defence publication D/Med (F&S) (2)710/1/1, Her Majesty's Stationary Office, LondonGoogle Scholar
  30. Karlsson N, Cassel G, Fängmark I, Bergman F (1986) A comparative study of the acute inhalation toxicity of smoke from TiO2-hexachloroethane and Zn-hexachloroethane pyrotechnic mixtures. Arch Toxicol 59: 160–166Google Scholar
  31. Kraybill HF (1985) Assessment of human exposure to environmental contaminants with special reference to cancer. In: Clayson DB, Krewski D, Munroe I (eds) Toxicological risk assessment, Vol 2. CRC Press Inc, Boca Raton, Florida, p 24Google Scholar
  32. Macaulay MB, Mant AK (1964) Smoke bomb poisoning: a fatal case following the inhalation of zinc chloride smoke. J R Army Med Coll 110: 27–32Google Scholar
  33. Manning PJ (1976) Neoplastic disease. In: Wagner JE, Manning PJ (eds) The biology of the guinea pig. Academic Press, New York, pp 211–225Google Scholar
  34. Marrs TC (1984) Histological changes produced by exposure of rabbits and rats to smokes produced from red phosphorus. Toxicol Lett 21: 141–146Google Scholar
  35. Marrs TC, Clifford WE, Colgrave HF (1983a) Pathological changes produced by exposure of rabbits and rats to smokes from mixtures of hexachloroethane and zinc oxide. Toxicol Lett 19: 247–252Google Scholar
  36. Marrs TC, Colgrave HF, Cross NL (1983b) A repeated dose study of the toxicity of technical grade dibenz-(b.f.)-1,4 oxazepine in mice and hamsters. Toxicol Lett 17: 13–21Google Scholar
  37. Marrs TC, Colgrave HF, Cross NL, Gazzard MF, Brown RFR (1983c) Repeated dose inhalation toxicology of CS (2-chlorobenzylidene malononitrile) in three species of laboratory animal. Arch Toxicol 52: 183–198Google Scholar
  38. Marrs TC, Colgrave HF, Gazzard M, Brown RFR (1984) Inhalation toxicity of a smoke containing solvent yellow 33, disperse red 9 and solvent green 3 in laboratory animals. Hum Toxicol 3: 289–308Google Scholar
  39. Marrs TC, Colgrave HF, Cross NL, Edginton JAG, Morris BC (1988) Inhalation toxicity of a coloured smoke and the mutagenicity of its constituent dyes, Solvent yellow 33 (CI 47000) and Disperse orange 11 (CI 60700) in the Ames test. J Hazardous Materials 17: 269–285Google Scholar
  40. Matarese SL, Matthews JI (1986) Zinc chloride (smoke bomb) inhalational lung injury. Chest 89: 308–309Google Scholar
  41. Milliken JA, Waugh D, Kadish ME (1963) Acute interstitial pulmonary fibrosis caused by a smoke bomb. Can Med Assoc J 88: 36–39Google Scholar
  42. Pare CMB, Sandler M (1954) Smoke bomb pneumonitis: description of a case. J R Army Med Coll 100: 320–322Google Scholar
  43. Pearse AGE (1985) Histochemistry, theoretical and applied, Volume 2. Churchill-Livingstone, Edinburgh, New YorkGoogle Scholar
  44. Schenker MB, Speizer FE, Taylor JO (1981) Acute upper respiratory symptoms resulting from exposure to zinc chloride aerosol. Environ Res 25: 317–324Google Scholar
  45. Shimkin MB, Weisburger JH, Weisberger EK, Gubareff N, Suntzeff V (1966) Bioassay of 29 alkylating chemicals in the pulmonary tumor response in Strain A mice. J Natl Cancer Inst 36: 915–935Google Scholar
  46. Shimkin MB, Stoner GD (1975) Lung tumors in mice: application to carcinogenesis bioassay. Adv Cancer Res 21: 1–49Google Scholar
  47. Snedecor GW, Cochran WG (1971) Statistical tests. Iowa State University Press, Iowa, p 246Google Scholar
  48. Snell KC (1965) Spontaneous lesions of the rat. In: Ribelin WE, McCoy JR (eds) The pathology of laboratory animals. Charles C Thomas, Springfield, Illinois, pp 241–300Google Scholar
  49. Stewart HL, Dunn TB, Snell KC, Deringer MK (1979) Tumours of the respiratory tract. In: WHO Monographs on the Pathology of tumours of laboratory animals, Vol 1, The mouse. International Association for Research on Cancer, Lyons, France, pp 251–270Google Scholar
  50. Stookey JL, Moe JB (1978) The respiratory system. In: Bernischke K, Garner FM, Jones TC (eds) The pathology of laboratory animals, Vol 2. Springer, New York, pp 1075–1082Google Scholar
  51. Ulrich CE, Marold BW (1979) Pulmonary disposition of aerosols in individual and group caged rats. Am Indust Hyg Assoc J 40: 633–636Google Scholar
  52. US Army (1987). United States Army Corps of Engineers. Construction Engineering Laboratory. USA-CERL Technical Report N-87/26 September 1987. Department of Defense, Washington D.C.Google Scholar
  53. Weeks MH, Angerhofer RA, Bishop R, Thomasino J, Cope CR (1979) The toxicity of hexachloroethane in laboratory animals. Am Indust Hyg Assoc J 40: 187–199Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • T. C. Marrs
    • 1
  • H. F. Colgrave
    • 1
  • J. A. G. Edginton
    • 1
  • R. F. R. Brown
    • 1
  • N. L. Cross
    • 1
  1. 1.CDE Porton DownSalisburyUK

Personalised recommendations