More than 40 experts and observers from more than 14 countries met at an IARC Working Group meeting in Lyon, France, during 20-27 March 2018, in order to evaluate the cancer evidence for quinoline, styrene and styrene oxide for the IARC Monograph No. 121.
As always participation in an IARC WGs is hard, intense but also fruitful work. A picture of the “fresh” participants early at day 1, before the work really began in 4 subgroups and plenum, is shown below. I am the grey man in the last row:
Yesterday a summary of our evaluations has been published online by the Lancet Oncology. My even shorter summary is presented below.
Quinoline is present as a contaminant in coal tars, creosote, tobacco smoke and air pollution. It is a high production volume chemical used as a solvent and intermediate for production of a variety of drugs and dyes, including “quinoline yellow”.
No data were available on cancer or toxicokinetics of quinoline in humans. Neither, quantitative data on human exposures were available.
In animal studies with mice and rats quinoline induced rare malignant tumors with high incidence at the lowest dose tested. The tumors occurred with short latency and caused early death. Quinoline is certainly a very potent animal carcinogen.
Although quinoline was considered genotoxic, and there was sufficient evidence of carcinogenicity in experimental animals, the complete lack of human data implied in the IARC assessment scheme only a classification as “possibly carcinogenic to humans” (Group 2B).
Based on the fact that no data results in a lower classification than inadequate data, there will be no incentive, unfortunately, for the industry to try to produce the missing human data.
Styrene and styrene oxide have been evaluated by other IARC WGs several times before, thus the present evaluation was a re-evaluation/update.
Styrene is present in tobacco smoke and air pollution. Styrene is one of the most important industrial chemicals, which primarily is used to produce various common polystyrene polymers and co-polymers.
Styrene 7,8-oxide is the principal metabolite of styrene in humans, and styrene oxide is found together with styrene in workplace air from the reinforced plastics and rubber industries. Styrene oxide is manufactured by oxidation of styrene and is used in epoxy resins.
The most informative epidemiological studies of cancer were in large occupational cohorts (of >100000 workers) in the reinforced plastics industry, where styrene exposure levels were highest. Some recent Danish studies were here in focus.
The WG noted an increased incidence or mortality of lymphohaematopoietic malignancies as a whole and for specific subtypes with increasing cumulative styrene exposure for a latency period of 15 years. An increased incidence of some rare nose cancers were also indicated.
In experimental animals styrene was carcinogenic in the lungs of male mice, in the liver of female mice and in the breast of female rats.
In experimentasl animals styrene oxide caused an increased incidence of malignant forestomach tumors in mice and rats.
Styrene was classified as “probably carcinogenic to humans” (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals and supported by strong evidence of a mechanism also operating in humans. That was the metabolic formation of the electrophile genotoxic, styrene 7,8-oxide.
Styrene 7,8-oxide was also classified as “probably carcinogenic to humans” (Group 2A) based on inadequate evidence of carcinogenicity in humans but sufficient evidence of genotoxicity and carcinogenicity in experimental animals.