Dibromomethane

Endpoint summary

Additional information

A standard toxicokinetic study could not be located. However, several scientific publications are available. All of them are well described and reliable (Klimisch2). Some of these publications are also cited in the US EPAHealth and Environmental Profile for Methylene Bromide (1987).

 Absorption-

Oral route-Data regarding the gastrointestinal absorption of dibromomethane could not be located in the available literature. However, systemic effects which were observed following oral exposure points out that the substanceare absorbed by this route.

Inhalation route- Rats exposed by inhalation to 100mmol/ kg (17.4 mg/kg) dibromomethane in a closed rebreathing system exhaled ~70mmol/kg (~2mg/kg) of carbon monoxide above endogenous levels for 6 hours (Rodkey and Collison, 1977). Although these data indicate that dibromomethane was absorbed by the pulmonary route, some of the carbon monoxide production occurred in the lungs, as lung microsomes are capable of metabolizing dibromomethane to carbon monoxidein vitro.

Dermal route-McDougal et al. (1985) studied the dermal absorption of dibromomethane in male Fischer-344 rats in chambers that provided the rats with fresh air while their bodies were exposed to concentrations of dibromomethane ranging from 500-10,000 ppm. A jugular catheter provided the means for obtaining serial blood samples in which plasma levels of dibromomethane and bromide were measured. Dibromomethane was detected in blood within 20 minutes of the start of exposure at all levels and the plasma levels were concentration related, indicating absorbance through the skin.

McDougal et al. (1986) presented a method to determine a skin:air partition coefficient (PC) for volatile organic chemicals. Skin:air PC determined for dibromomethane is 68.3. This high PC value indicates that dibromomethane quickly enters the skin.

McDougal and Whitehead (2001) showed that following short time showering and bathing exposures of isolated rat skin (Fischer 344 strain) with dimromomethane for up to 20 minutes (a diffusion cell experiment), the absorption of the chemical into the skin was greater than the penetration of the chemical through the skin during the exposure. The amount of chemical in the skin was approximately eight times the amount that was in the receptor solution. Therefore, the amount of the chemical in the skin is the most important part of the body burden during showering or bathing.

Distribution-Data regarding the distribution on dibromomethane could not be obtained from the literature. 

Metabolism- Dibromomethane was metabolized to carbon monoxide and inorganic bromidein vitroin the presence of rat hepatic microsomes, NADPH and molecular oxygen (Kubic and Anders, 1975, 1978). Microsomes from rat pulmonary and renal microsomes showed ~18 and ~5 %, respectively of the activity of the hepatic microsomes. Brain and splenic microsomes did not metabolize dibromomethane to carbon monoxide and inorganic bromide.

In vitrostudies with inhibitors and stimulators of cytochrome P-450 activity indicate that a cytochrome P-450 system is involved in the metabolism (Kubic and Andreas, 1975, Stevenes et al 1980).

Kubic and Ander (1975) confirmed that in the cytosolthe metabolic pathway of dihalomethane is to formaldehyde and inorganic bromide.

Administration of dibromomethane to ratsin vivoresulted in increased levels of carboxyhemoglobin, indicating metabolism of dibromomethane to carbon monoxide and inorganic bromide (Kubic et al. (1974).

Kubic et al (1974) administered 3 mmol/ kg (522mg/kg) dibromomethane by intraperitoneal injection to young adult male long-Evans rats and measured the increase in blood carboxyhemoglobin levels for 10 hours. At 4-5 hours, the carboxyhemoglobin level picked at ~14% of the total carboxyhemoglobin content of dibromomethane in rats. The level then declined in a biphasic manner over the next 5-6 hours. When the rats were injected intraperitoneally with 3 mmol/ kg dibromomethane once daily for 4 days, no evidence of accumulation of carboxyhemoglobin was found.

 In dermal exposure experiments by McDougl et al (1985), the bromide ion concentrations in plasma increased with increasing exposure concentration in a nonlinear manner, indicating that the metabolism of dibromomethane to inorganic bromide may become saturated at high exposure concentrations. 

          

 Rodkey and Collison (1977) reported that the rate of carbon monoxide exhalation by female rats exposed by inhalation to 100mmol/kg of dibromomethanefor up to 6 hours was increased 51 times above the rate of carbon monoxide exhalation by untreated rats.

Excretion-

The amount of carbon mono oxide exhaled by female rats which were exposed to dibromomethane increased (Rodkey and Collison, 1977), data regarding the percent of an oral or inhalation dose excreted from the body and feces, urine bile expired air or sweat could not be located in the available literature.