Relevance of chemical structure and cytotoxicity to the induction of chromosome aberrations based on the testing results of 98 high production volume industrial chemicals.
Over a 6-year period (1991-1996), the chromosomal aberration testing of high production volume (HPV) industrial chemicals had been conducted using Chinese hamster lung (CHL/IU) cells according to OECD HPV testing program and the national program in Japan. A total of 98 chemicals were tested for the induction of chromosome aberration (CA), consisting of structural CA and polyploidy. Of the 98 chemicals, structural CA and/or polyploidy were induced by 39 chemicals (40%). Anilines and phenols tended to induce only structural CA. p-tert-Butylphenol had a peculiar feature in inducing not only structural CA but also polyploidy at considerably high frequency (93.2%) after continuous treatment for 48 h, posing an aneugenic potential. Not all, but six of 11 carboxylic acids or esters also showed the simultaneous induction of structural CA and polyploidy. The majority of organic phosphates, alcohols or ethers, alkyl benzenes and non-cyclic alkanes had no CA induction activity. For chemicals which were negative in the bacterial reverse mutation assay (Ames test), the proportion of the chemicals that induced CA at a severely cytotoxic dose (doses manifesting more than 50% cytotoxicity) was similar to that of the CA-negative chemicals manifesting severe cytotoxicity, suggesting that severely cytotoxic chemicals do not always induce CA.
Kusakabe
Hirokazu
H
Laboratory of Cell Toxicology, Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan.
Yamakage
Kohji
K
Wakuri
Shinobu
S
Sasaki
Kiyoshi
K
Nakagawa
Yuzuki
Y
Watanabe
Mika
M
Hayashi
Makoto
M
Sofuni
Toshio
T
Ono
Hiroshi
H
Tanaka
Noriho
N
D000438:Alcohols; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D002460:Cell Line; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D010636:Phenols; D010710:Phosphates / Q000378:metabolism; D011123:Polyploidy
D000438:Alcohols; D002264:Carboxylic Acids; D004952:Esters; D009153:Mutagens; D010636:Phenols; D010710:Phosphates; D004247:DNA