Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
71 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

There is limited information on the toxicity of RDX in humans; the database consists of studies of workers exposed to RDX dust, soldiers using C-4 (a plasticized explosive containing 91% RDX) as a cooking fuel, and case reports of individuals ingesting RDX.

Most of these studies involve acute exposure to RDX and provide limited exposure information. Neurologic dysfunction, primarily seizures and convulsions, was the most commonly reported effect. The seizures/convulsions typically occurred within several hours of exposure, and in some cases, convulsions were noted for several days after exposure. Other neurological symptoms that have been observed in humans include disorientation, lethargy, muscle twitching, and marked hyperirritability.

Studies in laboratory animals support neurological effects as a sensitive end point of RDX. Seizures, convulsions, and tremors have been reported in rats, deer mice, dogs, and monkeys orally exposed to RDX for acute durations. As with human exposure, the clonic-tonic convulsions and seizures are often observed shortly after exposure; however, a study in monkeys did not report seizures in some of the animals until after 34–57 doses of 10 mg/kg/day. In acute-exposure studies, the lowest adverse effect level for seizures and convulsions was 17 mg/kg/day, with no seizures at 12.5 mg/kg/day. In addition to these neurological effects, decreases in motor activity and impaired learning were observed in rats following administration of a single gavage dose of 12.5 mg/kg/day.


Justification for selection of acute toxicity – oral endpoint
No studies were located regarding death in humans after oral exposure to RDX.
Deaths were reported in animals following acute exposures to RDX.
Three out of 12 rats died during induced seizures following acute exposure to 50 mg/kg RDX, which was administered by gavage (Burdette et al, 1988).
LD50 values for single gavage doses were:
- 71–118 mg/kg in rats (Dilley et al, 1978; Cholakis et al, 1980),
- 86–97 mg/kg in mice (Dilley et al, 1978; Cholakis et al, 1980),
- and 136–319 mg/kg in deer mice (Smith et al, 2007).
Apparent age-related differences in LD50 values were found in deer mice; the LD50 values were 136, 319, and 158 mg/kg in 21-, 50-, and 200-day-old mice (Smith et al, 2007). Miniature swine died (2/10) following single gavage doses of 100 mg/kg (Schneider et al, 1977).
Rat dams that were fed 20 mg/kg/day of RDX during gestation had mortality rates of 24% (Cholakis et al, 1980).

Justification for selection of acute toxicity – inhalation endpoint
REACH annexes VII to X ask to perform two acute toxicity studies by two relevant routes, one being oral, except for gases. The substance is not a gas and two routes have been tested, oral and dermal. Therefore, testing by inhalation is not required.
However one non-reliable data exist. Death attributed to impairment of the respiratory system was observed in rabbits and guinea pigs exposed to an unspecified concentration of RDX.

Furthemore, according to Reach Annex VIII end point 8.5.2, the study does not need to be conducted if inhalation is unlikely taking into account the substance particles of an inhalable size. The granulometry study shows that <10% by mass of HMX particles are <10µm, therefore an acute inhalation study is not warranted. Furthermore, >77% by mass of particles are > 100 µm, this is accepted as a non-respirable fraction.

Justification for selection of acute toxicity – dermal endpoint
No studies were located regarding death in humans after dermal exposure to RDX.
Deaths were observed in rabbits receiving repeated dermal applications of 37.5 mg/kg/day RDX in cyclohexanone (1/6 deaths) or 27 mg/kg/day RDX in acetone (2/6) deaths; no gross pathological effects were seen (McNamara, 1974).
Because of the lack of data presented, it is difficult to determine whether RDX alone was responsible for the deaths reported in this study.
Dermatitis was observed in rabbits exposed once to 27 mg/kg RDX in acetone, 37.5 mg/kg RDX in cyclohexanone, or 165 mg/kg RDX in DMSO (McNamara et al, 1974); the dermatitis persisted for at least 30 days and was most pronounced in the rabbits exposed to 165 mg/kg RDX in DMSO. Slight erythema was noted in guinea pigs exposed once to 1,000 mg/kg (McNamara et al, 1974).
However, these local effects were limited and RDX was not considered as Irritating to skin (see Irritation / Corrosion chapter).

Justification for classification or non-classification

With oral LD50 values in rats between 50 to 300 mg/kg and a low observe adverse effect level of 17 mg/kg for seizures, RDX is considered as "Toxic by ingestion" and "Causes damage to organs (central nervous system) after a single exposure , according to the criteria of Regulation EC n°1272/2008 modified (CLP).

The classification of RDX is:

- Acute Toxicity Category 3; H301

- STOT SE Category 1; H370 (oral)