1-Chloromethylpyrene: a reference skin sensitizer and genotoxin.
1-Chloromethylpyrene (1-CMP) has been evaluated as a model mutagen and toxin related to the ultimate electrophiles derived from benzo[a]pyrene and 1-nitropyrene. It was mutagenic to Salmonella (greater than 100 pg/plate) and exceptionally reactive to DNA when assessed by the 32P-postlabelling technique. 1-CMP was inactive in a mouse bone micronucleus assay when administered by gavage, probably due to hydrolysis, whose kinetics have been studied (t1/2 approximately 23 min at 37 degrees C). However, as expected, it was a potent skin toxin as determined by its activity as a mitogen to mouse skin and its contact allergenicity, as determined using the local lymph node proliferative assay. It is concluded that 1-CMP will probably be a potent human skin carcinogen and contact allergen.
Ashby
J
J
ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, Great Britain.
Gallagher
J E
JE
Kohan
M
M
Tinwell
H
H
Kimber
I
I
Paton
D
D
Callander
R D
RD
Chouroulinkov
I
I
D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000187:drug effects; D005260:Female; D006868:Hydrolysis; D008198:Lymph Nodes / Q000187:drug effects; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015162:Micronucleus Tests; D009153:Mutagens; D010761:Phosphorus Radioisotopes; D011721:Pyrenes / Q000633:toxicity*; D012475:Salmonella / Q000187:drug effects; D012627:Sebaceous Glands / Q000187:drug effects; D012867:Skin / Q000187:drug effects*
D002273:Carcinogens; D009153:Mutagens; D010761:Phosphorus Radioisotopes; D011721:Pyrenes; C052575:1-chloromethylpyrene; D004247:DNA