Wednesday, April 08, 2009

Myrcene Carcinogenesis - Another Facet of the Alpha 2 Houdini Risk Assessment



NTP TECHNICAL REPORT
ON THE
TOXICOLOGY AND CARCINOGENESIS
STUDIES OF β-MYRCENE
(CAS NO. 123-35-3)
IN F344/N RATS AND B6C3F1 MICE
(GAVAGE STUDIES)

[beta-myrcene is a C10 terpene, 3 double bonds, two of which are conjugated. It's a natural product, essential oil, related to limonene (tested at NTP), turpentine, etc]

[Tested at 1.0 mg/kg and below in rats (all the 1 mg/kg male rats died) and mice of both genders]

"...
In the standard evaluation of the kidney, the incidence of renal tubule adenoma was significantly increased in 0.5 g/kg male rats, and the combined incidences of renal tubule adenoma or carcinoma were significantly increased in 0.25 and 0.5 g/kg males. In both the extended evaluation and the combined standard and extended evaluations, the incidences of renal tubule adenoma and the combined incidences of renal tubule adenoma or carcinoma were significantly increased in the 0.25 and 0.5 g/kg groups of males. The incidences of renal tubule nephrosis (nephrosis) were markedly increased in all dosed groups of both sexes except in 0.25 g/kg females. The incidences of papillary mineralization in 0.25 and 0.5 g/kg males were significantly increased. Significantly increased incidences of nephropathy occurred in dosed females, and the severity was increased in the 0.5 and 1 g/kg males and females. ...

[MICE] ...
The incidences of liver neoplasms were significantly increased in 0.25 and/or 0.5 g/kg males and 0.25 g/kg females. Liver neoplasms included hepatocellular adenoma and hepatocellular carcinoma in males and females and hepatoblastoma in males. The incidences of hepatocellular hypertrophy were significantly increased in 0.5 g/kg males and females, as was the incidence of mixed cell focus in 0.5 g/kg females.
The incidences of bone marrow atrophy and lymph node follicle atrophy in the spleen were significantly increased in 0.5 g/kg females. ..

"Conclusions Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of β-myrcene in male F344/N rats based on increased incidences of renal tubule neoplasms. There was equivocal evidence of carcinogenic activity of β-myrcene in female F344/N rats based on increased incidences of renal tubule adenoma. There was clear evidence of carcinogenic activity of β-myrcene in male B6C3F1 mice based on increased incidences of liver neoplasms. There was equivocal evidence of carcinogenic activity of β-myrcene in female B6C3F1 mice based on marginally increased incidences of hepatocellular neoplasms.

Administration of β-myrcene induced nonneoplastic lesions in the kidney of male and female rats, nose of male rats, and liver of male and female mice."

>>>>>>>>>>>>>>>>

BrooklynDodger(s) comment: The competition for the title "Mother" of all Houdini Risk Assessments is stiff, but the alpha-2 hypothesis is in the running. Adopting alpha 2 allowed industry to make the risk of gasoline (and later MBTE) to disappear and thus escape from imposing controls which would be far reaching.

In plain terms, if a chemical causes kidney tumors in male rats only, and the kidney tumors are accompanied by nephropathy in the male rats only (of a particular kind called hyaline droplet), then the tumors are considered to be irrelevant to human risk. That's consensus, although there is a considerable group of alpha-2 deniers (which include the Dodger(s).

Actually, this "morning after the bioassay pill" to abort risk assessment by killing the hazard identification doesn't really apply to gasoline, the subject of another post.

Myrcene is a terpene, non-cyclic C10 hydrocarbon. Actually, it's got a conjugated double bond, an analogy to butadiene. Myrcene dosing produced clear evidence for kidney cancer in male rats and equivocal in females, but nephrophathy in both. And, clear evidence of liver tumors in male mice and equivocal in the females.

So Myrcene ought to be a 2B at IARC and reasonably anticipated at NTP.





No comments: