Table 6.
NTP studies where at least one sex had MNCL classified as some evidence of carcinogenicity.
| Two-year study highlights | Overall MNCL incidencesa | MNCL historical control data | Authors’ commentary |
|---|---|---|---|
| Dibromoacetic acid (NTP TR 537) | |||
| This drinking water study was started in March 2000 with good survival in treated groups. There was some evidence of carcinogenicity based on tunica vaginalis mesotheliomas in males with equivocal evidence for MNCL in males. MNCL was the only tumor response in females and was called some evidence of carcinogenicity. Liver and lung tumors were present in treated B6C3F1 mice. | F 11/50 (22%), 13/50 (26%), 16/50 (32%), 22/50 (44%)M 17/50 (34%), 31/50 (32%), 24/50 (48%), 13/50 (26%) | F 23.5% ± 4.4% (range 20–30%)M 31.6% ± 3.3% (range 26–34%) | There was significant debate regarding the MNCL call of some evidence of carcinogenicity for females during the formal public peer review and that discussion continued on the following day. It was noted that the historical control range was possibly artificially tight being based on only four studies. NTP downgraded the evidence of carcinogenicity from some to equivocal in males based on the peer review discussion. |
| Dichlorvos (NTP TR 342) | |||
| There was good survival in this corn oil gavage study started in January 1981 with MNCL in males and pancreatic acinar tumors in male and female rats. Forestomach tumors were present in male and female treated B6C3F1 mice. | F 17/50 (34%), 21/50 (42%), 23/50 (46%)M 11/50 (22%), 20/50 (40%), 21/50 (42%) | F (Not provided in TR)M 9% ± 7% (range 2–18%) (Laboratory)15% ± 9% (range 2–44%) (NTP) | There was discussion during the formal public peer review pointing out the higher than usual concurrent control incidence of MNCL. The MNCL response was considered contributory to the call of some evidence of carcinogenicity. |
| Dimethyl morpholinophosphoramidate (NTP TR 298) | |||
| In this corn oil gavage study started in April 1980, there was reduced survival in high-dose rats. The only tumor response attributed to treatment was some evidence of carcinogenicity for MNCL in both male and female rats. No treatment-associated tumors were present in B6C3F1 mice. | F 9/50 (18%), 13/5 (26%), 12/49 (24%), 18/50 (36%)M 14/50 (28%), 21/50 (42%), 19/50 (38%), 25/50 (50%) | F 29.3% ± 13.0% (range 16–42%) (Laboratory)16.1% ± 8.9% (range 2–42%) (NTP)M 17.3% ± 11.7% (range 4–26%) (Laboratory)12.2% ±7.6% (range 2–26%) (NTP) | There was increased incidence of MNCL in the high-dose for both sexes and the severity of the MNCL was greater in treated than in control rats. On the other hand, the MNCL incidence in male controls exceeded the historical control while that for the female controls was lower than the mean historical control. There was some concern voiced regarding the MNCL call during the formal public peer review. |
| Hydroquinone (NTP TR 366) | |||
| There was good survival in this water gavage study started in August 1982. Renal tubular tumors in the male rats and MNCL in females were considered some evidence of carcinogenicity. Liver tumors were present in female treated B6C3F1 mice. | F 9/55 (16%), 15/55 (27%), 22/55 (40%)M 28/55 (51%), 26/55 (47%), 31/55 (56%) | F 25% ± 15% (range 8–46%) (NTP)M (Not provided in TR) | It is noted that the control incidence of MNCL is lower than the historical control incidence. Some concern regarding the MNCL call was raised during the formal public peer review period due to the high and variable control incidence of MNCL. Most of the discussion, however, was focused on the male renal tumor response. |
| Iodinated glycerol (NTP TR 340) | |||
| This water gavage study was started in April 1981 and there was reduced survival in high-dose male rats plus some evidence of carcinogenicity for MNCL and thyroid follicular carcinomas. There were no treatment-related tumors in female rats. Female B6C3F1 mice had some evidence of carcinogenicity. | F 15/50 (30%), 14/50 (28%), 14/50 (28%)M 14/50 (28%), 29/50 (58%) 24/50 (48%) | F (Not provided in TR)M 39% ± 16% (range 14–60%) | The call of some evidence of carcinogenicity was based largely on the MNCL response in the male rats since the incidences of the thyroid tumors & nasal adenomas were marginal. There was some discussion regarding the MNCL call raised during the formal public review of the study. It is noted that the MNCL incidences for males fall within the historical control range. |
| 2-Mercaptobenzothiazole (NTP TR 332) | |||
| There was reduced survival in treated male and high-dose females in this corn oil gavage study started in July 1981. The some evidence of carcinogenicity call in males was based on MNCL as well as preputial gland, pancreatic ascinar and adrenal pheochromocytomas. Females also had pheochromocytomas (some evidence). There was an equivocal liver tumor response in female B6C3F1 mice. | F 6/50 (12%), 14/50 (28%), 9/50 (8%)M 7/50 (14%), 16/50 (32%), 3/50 (6%) | F 19% ± 9% (range 4–42%) (NTP)M 14% ± 8%(range 2–28%) (NTP) | The MNCL call of some evidence of carcinogenicity was discussed during the formal public peer review and there were two opinions expressed that the levels of evidence for carcinogenicity in males should be equivocal. The MNCL response was present only at the low dose with poor survival at the high dose. |
| Riddelliine (NTP TR 508) | |||
| Riddelliine, a gavage study starting in 1996, had an unbalanced design with only a control and high-dose group for male rats. Both genders of rats are listed as clear evidence of carcinogenicity for MNCL. The male rat study was terminated at 72 weeks due to a high incidence (clear evidence) of hepatic hemangiosarcomas. Male B6C3F1 mice had hepatic hemangiosarcomas while females had lung tumors. | F 12/50(24%), 8/50 (16%), 13/50 (26%), 18/50 (36%), 18/50 (35%), 14/50 (28%)M 2/50 (4%), 9/50 (18%) | F 29.1% ± 8.4% (range 16–42%)M Not applicable. Early study termination. | The overall incidences of MNCL were within the historical control range. We have included riddelliine in our listing of some evidence based on comments made during the formal public peer review that the female MNCL response by itself should be classified as some evidence of carcinogenicity. In light of the early termination and high incidence of hepatic hemangiosarcomas in treated males, attributing any levels of evidence for MNCL carcinogenicity is questionable. |
TR: NTP Technical Report; M: Male; F: Female; MNCL: Mononuclear cell leukemia.
a = Tumor incidences arranged starting with controls and progressing through increased doses.