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Table 13 Selected neoplastic and non-neoplastic lung effects in 2 year inhalation studies of male and female F344/N rats and B6C3F1 mice exposed to nickel subsulphide, nickel oxide and nickel sulphate hexahydrate [3032]; and Wistar rats exposed to nickel metal powder [35]

From: New views on the hypothesis of respiratory cancer risk from soluble nickel exposure; and reconsideration of this risk's historical sources in nickel refineries

  F344/N rats B6C3F 1 mice
Ni species, dose and lung effects Male Female Male Female
Nickel subsulphide:     
   Dose in % of MTDa, b (0, 15, 100) (0, 15, 100) (0, 50, 100) (0, 50, 100)
   Chronic active inflammation rate (9/53, 53/53, 51/53) (7/53, 51/53, 51/53) (1/61, 52/59, 53/58) (1/58, 46/59, 58/60)
   Macrophage hyperplasia rate (9/53, 48/53, 52/53) (8/53, 51/53, 52/53) (6/61, 57/59, 58/58) (5/58, 57/59, 60/60)
   Alveolar/bronchiolar adenoma or carcinoma rate (0/53, 6/53, 11/53) (2/53, 6/53, 9/53)f None None
Nickel oxide:     
   Dose in % of MTDc (0, 25, 50, 100) (0, 25, 50, 100) (0, 25, 50, 100) (0, 25, 50, 100)
   Chronic inflammation rate (28/54, 53/53, 53/53, 52/52) (18/53, 52/53, 53/53, 54/54) (0/57, 21/67, 34/66, 55/69) (7/64, 43/66, 53/63, 52/64)
   Alveolar/bronchiolar adenoma or carcinoma rate (1/54, 1/53, 6/53, 4/52)f (1/53, 0/53, 6/53, 5/54) None (6/64, 15/66, 12/63, 8/64)
Nickel sulphate hexahydrate:     
   Dose in % of MTDd (0, 25, 50, 100) (0, 25, 50, 100) (0, 25, 50, 100) (0, 25, 50, 100)
   Chronic active inflammation rate (14/54, 11/53, 42/53, 46/53) (14/52, 13/53, 49/53, 52/54) (1/61, 2/61, 8/62, 29/61) (1/61, 7/60, 14/60, 40/60)
   Macrophage hyperplasia rate (7/54, 9/53, 35/53, 48/53) (9/52, 10/53, 32/53, 45/54) (6/61, 9/61, 35/62, 59/61) (7/61, 24/60, 53/60, 59/60)
   Neoplastic effects None None None None
  Wistar rats   
Nickel metal:     
   Dose in % of MTDe (0, 25, 100) (0, 25, 100)   
   Chronic inflammation rate (14/50, 44/50, 41/50) (16/50, 45/50, 45/54)   
   Neoplastic effects Noneg Noneg   
  1. a MTD: Maximum Tolerated Dose. b MTD [Ni3S2/m3]: 0.73 mg (rats); 1.2 mg (mice). c MTD ["green" NiO/m3]: 2.0 mg (rats); 3.9 mg (mice).
  2. d MTD [NiSO4.6H2O/m3]: 0.11 mg (rats); 0.22 mg (mice). e MTD [Ni metal/m3]: 0.4 mg (rats). f Includes squamous cell carcinoma. g Oller et al. (2008) [35] concluded that the treatment of nickel metal powder administered by inhalation 6 h/day, 5 days/week over a two-year period did not produce an exposure-related increase in tumors anywhere in the respiratory tract, including the nose.