Results of the main study

A) Rats

• Survival: Exposed male rats lived significantly longer than the sham-exposed control animals (number of animals surviving to the end of the study: GSM 25, 45*, 50*, 60* or CDMA 25, 43*, 56*, 43 at 0, 1.5, 3, and 6 W/kg)^a . Exposed female rats lived as long as the control animals except for the animals of the 6 W/kg CDMA-exposed group, which survived significantly longer (number of animals surviving to the end of the study: GSM 48, 53, 48, 57 or CDMA 48, 46, 50, 61 at 0, 1.5, 3, and 6 W/kg).

• Heart: In male rats, the incidence of malignant schwannomas of the heart increased with increasing GSM exposure (0, 2, 1, 5 cases at 0, 1.5, 3, and 6 W/kg) and CDMA exposure (0, 2, 3, 6* cases at 0, 1.5, 3, and 6 W/kg). This exposure-response trend was statistically significant for both modulations and for CDMA in the highest exposure group (6 W/kg) compared with sham exposure. In the female rats, there was neither a trend nor a significantly increased incidence for individual exposure levels (GSM: 0, 0, 2, 0 cases and CDMA: 0, 2, 0, 2 cases at 0, 1.5, 3, and 6 W/kg respectively). The incidence of schwannomas in other parts of the body was unremarkable.

  Significantly (*) increased incidences of right ventricular cardiomyopathies occurred at the highest CDMA and the two highest GSM exposure levels in male rats (GSM: 54, 62, 72*, 74* cases and CDMA: 54, 45, 62, 74* cases at 0, 1.5, 3, and 6 W/kg) as well as in female rats (GSM: 4, 9, 14*, 15* cases at 0, 1.5, 3, and 6 W/kg) compared with sham-exposed controls.
  Increases in the incidence of Schwann cell hyperplasias (possible precancerous stage of schwannomas in the heart) in the male (GSM: 0, 1, 0, 2 cases and CDMA: 0, 0, 0, 3 cases at 0, 1.5, 3, and 6 W/kg) and female rats (only for CDMA: 0, 1, 1, 1 cases at 0, 1.5, 3, and 6 W/kg) were observed compared with controls. However, these were not significant.

• Brain: In male rats, increased incidences of malignant gliomas were found in all exposed groups compared with the control group at GSM modulation (0, 3, 3, 2 cases at 0, 1.5, 3, and 6 W/kg). There was also a significant trend with increasing exposure to CDMA modulation (0, 0, 0, 3 cases at 0, 1.5, 3, and 6 W/kg). In female rats, increases in the incidence of malignant gliomas (GSM: 0, 3, 0, 0 cases and CDMA: 0, 0, 0, 1 cases at 0, 1.5, 3, and 6 W/kg) occurred in only a few exposure levels, all of which were not significant.

  Increased incidences of glial cell hyperplasia (possible precancerous stage of malignant glioma) occurred in most exposed groups of both sexes. However, these were not significant.

• Adrenal medulla: In male rats, incidences of benign pheochromocytomas (GSM: 10, 23*, 25*, 14 cases at 0, 1.5, 3, and 6 W/kg) as well as benign, malignant, and complex pheochromocytomas (GSM: 11, 24*, 28*, 14 cases at 0, 1.5, 3, and 6 W/kg) were significantly increased but only at GSM modulation. In female rats, the incidence of benign pheochromocytomas (GSM) was predominantly only slightly elevated (GSM: 1, 3, 3, 2 cases and CDMA: 1, 7, 3, 4 cases at 0, 1.5, 3, and 6 W/kg) as well as benign, malignant, and complex pheochromocytomas (CDMA: 1, 9*, 5, 4 at 0, 1.5, 3, and 6 W/kg).
• Kidney: In male rats, the severity of chronic progressive nephropathy in all exposed groups (GSM and CDMA) was lower than in the sham-exposed control group at equal incidence rates. For a number of possible secondary side effects of chronic progressive nephropathy, significantly reduced incidence rates were observed in all exposed groups of male rats (GSM and CDMA).
• Other organs: Occasionally significantly increased incidences of unclear significance: for example, for benign or malignant granular cell tumours, adenomas and carcinomas of the prostate gland, adenomas of the pituitary gland, and pancreatic islet cell adenoma or carcinoma (GSM) as well as for adenomas of the pituitary gland and hepatocellular adenomas or carcinomas of the liver (CDMA).

B) Mice

• Survival: The survival probability in most groups of male and female mice did not differ significantly from the sham-exposed control group.
• Heart, brain, and adrenal medulla: In contrast to rats, malignant schwannomas of the heart, malignant gliomas, and diseases of the adrenal medulla in mice showed neither a trend with increasing exposure nor significant increased incidences in the individual exposure levels compared with sham-exposed controls.
• Other organs: Occasionally (significantly) increased incidences or trends of unclear significance: Liver tumours, skin tumours, and lung tumours in male mice; malignant lymphomas in female mice.

A detailed list of further results from the main study can be found in Annex 2: Study design and results of the NTP main study.

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^a) significant results are marked with *.