19085-1701857-UL_Prop_65_Test_Results_2019

CA Prop 65 Cumene NSRL February 11, 2019 Page 5 | 12
Studies in rats
Groups of 50 male and 50 female F344 rats were exposed to 0, 250, 500 or 1,000 ppm cumene
(> 99% pure) for 6 hours plus T90 (12 minutes) per day on 5 days per week for 105 weeks.
Treatment-related increases were observed in the incidence of nasal tumours (respiratory
epithelial adenoma) in both males and females, and kidney tumours (renal tubule adenoma or
carcinoma) in males, with a dose-related increase in the incidende of nasal tumours in males,
with a concurrent increase in renal tubule hyperplasia and papillary mineralization in males,
which had a linear pattern. Furthermore, in a subchronic study in rats with five exposure groups
(62.5, 125, 250, 500 or 1000 ppm), dose-related increases in the severity of proximal tubular
hyaline droplet accumulation and regeneration occurred, together with increases in the
incidence of medullary granular casts and in the levels of α2u-globulin in males. Moreover,
males had a treatment-related increase in the incidence of testicular tumours (interstitial-cell
adenoma) (IARC 2013, NTP, 2009). Tumours of the nasal cavity and kidney and splenic
haemangiosarcomas are rare spontaneous neoplasms in experimental animals.
Table 2. Tumor Incidence in F344 Rats (NTP 2009)
Species/Sex
Tumor Type
Exposure Level (ppm)
Trend test
1
0
250
500
1,000
Male Rat F344
Nose
(respiratory
epithelial
adenoma)
0/50 7/50** 18/49** 10/50** p = 0.004
Kidney (renal
tubule adenoma)
1/50 4/50 5/50 4/50
Kidney (renal
tubule
carcinoma)
1/50 1/50 3/50 3/50
Kidney (renal
tubule adenoma
or carcinoma)
2/50 5/50 8/50* 7/50
Testis
(interstitial-cell
adenoma)
36/50 38/50 40/50 46/50** p = 0.006
Female Rat
F344
Nose
(respiratory
epithelial
adenomae)
0/50 5/48* 4/50 3/50
1 Exact test for linear trend
* p<0.05, poly 3-test
** p<0.01, poly 3-test