Perhydro-1,3,5-trinitro-1,3,5-triazine

Endpoint summary

Additional information

-         No studies were located regarding genotoxicity of RDX in humans following inhalation, oral, or dermal exposure to the chemical.

-         The in vitro mutagenicity of RDX has been investigated in several assays. The most recent and robust study according to OECD TG 471, including the E. coli WP2 uvrA strain, shows that RDX does not present mutagenic properties for the five strains tested for concentration up to the limit of solubility of the substance. Additionnal results of reverse mutation assays with Salmonella typhimurium conducted by several investigators with the test substance confirm these negative results (George et al, 2001; Pan et al, 2007; Cholakis et al, 1980). Other literature studies investigating bacterial strains such as Saccharomyces cerevisiae (Simmon et al, 1977), or Vibrio fischeri (Arfsten et al, 1994) also show negative results. A weakly positive result was found in one S. typhimurium strain (TA97a) (Pan et al, 2007), which is not confirmed in any other study. Overall weight of evidence shows that RDX does not present any mutagenic properties for bacteria in vitro.

-         In mammalian cells, forward mutation assays in mouse lymphoma L5178Y cells (Reddy et al, 2005) and hamster V79 lung cells (Lachance et al, 1999) were negative.

-         One in vitro study was located in which human fibroblasts (WI-38 cells) were incubated in the presence of RDX and tritiated thymidine (3H-TdR) to measure unscheduled deoxyribonucleic acid (DNA) synthesis (Dilley et al, 1978). RDX was tested in concentrations of up to 4,000 μg/mL both with and without metabolic activation. RDX was not found to significantly increase the rate of unscheduled DNA synthesis in the cells of any exposure group regardless of whether or not metabolic activators were present. Therefore, RDX was not observed to induce DNA damage in human fibroblasts under the conditions of the study (Dilley et al, 1978).

-         Only two in vivo animal studies were located and both provided negative evidence of mutagenicity. Cholakis et al (1980) investigated the effects of oral doses of RDX on dominant lethal mutations in rats. RDX was administered to the rats in the diet in doses of 0, 5, 16, or 50 mg/kg/day for 15 weeks. The males in each exposure group were then allowed to mate with untreated females for 2 weeks. There were no significant effects on the number of corpora lutea, implants, or live or dead embryos (Cholakis et al, 1980); no dominant lethal mutations were observed. In the other in vivo study, administration of a single gavage dose of up to 250 mg RDX/kg to male mice did not significantly increase the incidence of micronuclei in bone marrow cells examined 24 hours after dosing (Reddy et al, 2005).

-         Although the results of in vitro assays have been negative for RDX, some studies of environmental biotransformation products of RDX have reported positive results. For example, George et al. (2001) reported that hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3-dinitroso-5-nitro1,3,5,-triazine, were not mutagenic in S. typhimurium TA98 or TA100 with or without metabolic activation, but hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) was weakly genotoxic in strain TA100 but negative in strain TA98. Studies conducted by Pan et al. (2007) showed that in the presence of metabolic activation, both MNX and TNX were mutagenic in S. typhimurium TA97a, weakly mutagenic in strain TA102, and not mutagenic in strain TA98; in addition, TNX was weakly mutagenic in strain TA100 in the presence of metabolic activation. Pan et al. (2007) also reported that neither MNX nor TNX were mutagenic in S. typhimurium TA97a in the absence of metabolic activation. Collectively, the available information suggests that RDX is not a mutagenic substance, but some of its environmental biotransformation products may be of concern, especially since they have been identified as metabolic products in mammals (Major and Reddy, 2007).

 

Short description of key information:

RDX is not mutagenic for in vitro and in vivo mammalian systems.

 

Endpoint Conclusion: No adverse effect observed (negative)