Calcium cyanamide was first synthesized in 1898 and became one of the earliest successes in nitrogen fixation. The commercially formulated product contains approximately 65% calcium cyanamide, which is 20 to 24% nitrogen. For most of the 20th century it has been used as a fertilizer, and also as a cotton defoliant, herbicide, and soil insecticide. Its use as a fertilizer has diminished in recent years due to the introduction of other compounds, so that the chief industrial uses of calcium cyanamide today stem from the reactivity of the nitrile group. Calcium cyanamide can be dimerized to dicyandiamide, an intermediate for melamine, one of the basic ingredients in amino plastics and resins. Other products prepared from calcium cyanamide include urea, thiourea, and guanidine. Fusion of calcium cyanamide with sodium chloride produces calcium cyanide, which is required for ore processing and the production of ferrocyanides. Calcium cyanamide is added to pig iron to impart nitrogen and to remove sulfur from steel.
A bioassay of formulated calcium cyanamide for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered a commercial formulation containing 63% calcium cyanamide in the diet at one of two doses, either 100 or 200 ppm for the males and either 100 or 400 ppm for the females, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical at one of two doses, either 500 or 2,000 ppm, for 100 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of administration of the test chemical.
Mean body weights of the dosed rats and mice were only slightly lower than those of corresponding controls, except for the low-dose female mice, whose mean body weights were unaffected by the test chemical. Mortality was dose related only in male mice. Survival was 70% or greater in all dosed and control groups of each species and sex at the end of the bioassay, and sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. Both rats and mice may have been able to tolerate higher doses.
No tumors occurred in the dosed rats of either sex at incidences that could clearly be related to administration of the calcium cyanamide. However, in the subchronic studies performed with the rats, calcium cyanamide was found to cause diffuse follicular hyperplasia of the thyroid, with periglandular fibrosis and prominent periglandular vascularity.
In male mice, hemangiosarcomas were dose related in the males (P=0.006); however, in direct comparisons, incidences in the individual dosed groups were not significantly higher than those in the control group (controls 1/20 (5%); low-dose 2/50 (4%); high-dose 10/50 (20%)). The incidence of these tumors in historical-control male B6C3F1 mice was (13/323 (4%)), and the highest incidence observed was 2/19 (10%). In female mice, lymphomas or leukemias were dose related (P=0.009), and in a direct comparison the incidence of these tumors in the high-dose group was significantly higher (P=0.006) than that in the control group (controls 1/20 (5%); low-dose 11/46 (24%); high-dose 18/50 (36%)); however, the incidence of the lymphomas or leukemias in historical-control female B6C3F1 mice was 67/324 (21%), suggesting that the incidence of these tumors in the matched-control group of the present bioassay may have been abnormally low. Thus, neither the incidences of hemangiosarcomas of the circulatory system in male mice nor of lymphomas or leukemias in the female mice can clearly be related to administration of the test chemical.
It is concluded that under the conditions of this bioassay, the test formulation of calcium cyanamide was not carcinogenic for F344 rats or B6C3F1 mice of either sex