Methyl isothiocyanate

Endpoint summary

Description of key information

Some studies were availalble in humans.

Additional information

Study of Alexeef (1994) - A cohort study :

A tank car derailement in northern California in 1991 spilled metam sodium into sacramento River and released its breakdown product, methyl isothiocyanate into the air. Over 240 individuals reported symptoms such as eye and throat irritation, dizziness, and shortness of breath. Measured methyl isothiocyanate levels ranged from 0.2 -37 ppb and estimated peak levels ranged from 140 -1600 ppb.

Study of Shama (1981) - Suicide case :

A 23-year-old chemistry student (woman) swallow 50 mg methyl isothiocyanate in drinking water to suicide her. Immediately after ingestion she had noticed severe retrosternal burning and epigastric pain and begun to vomit repeatedly. A few minutes later she began generalised tonic and clonic seizures and became unconscious. She was admitted deeply comatose and with pulse 98/min and blood presssure 90/60 mmHg. Chest, heart, and abdomen were normal. The pupils were slightly dilated but equal in size and reacted sluggishly to light. There was complete loss of all reflex and motor activity including oculocephalic reflex. Gastric lavage was performed with sodium thiosulphate, and sodium nitrite and sodium thiosulphate were given intraveinously diapezam, and she was put on respirator. Peritoneal dialysis was instituted about one hours after admission. After medical treatment, she continued to deteriorate with a further fall in blood pressure, however, and died about eight hours after admission. Necropsy a few hours later showed extensive mucosal necrosis of oesophagus, stomach, and proximal part of duodenum. Other organs showed only evidence of shock.

Study of Richter (1980) : Sensitisation data

Richter (1986) recounted a number of dermatitis patients that showed positive patch test reaction to Vapam (metam sodium), concluding that the initial effector must have been methylisothiocyanate. One patient, exposed to dazomet through rubber boots, developed burns and a bullous eruption again one year later A further complication, "hypersensitivity-hepatitis of nonspecific type" was diagnosed after liver biopsy. While conditioning exposure to oral contraceptives was implicated in this response, Richter concluded that methylisothiocyanate absorption through the skin was also involved. Indeed, "such side effects must be considered if large areas of skin have been affected".

Lowit (2006): eye irritation

In order to determine the no-observed-adverse-effect-level (NOAEL) for human eye irritation produced by methyl isothiocyanate vapors, as well as its odor threshold, human volunteers were exposed to air concentrations of methyl isothiocyanate in a laboratory setting at different times of exposure. A specialized olfactometer was used which permitted the operator to dispense the test material through a manifold system. The odor threshold was determined to be 1.7 ppm (5 mg/m3). The olfactometer was adjusted to include a goggle system; this was then used to deliver methyl isothiocyanate during the eye irritation portion of the study. Five parameters were used to ascertain an irritation response: 1. the subjects’ subjective estimation of irritation (using the “Likert” scale); 2. photographs of the subjects’ eyes prior to and after exposure; 3. blink rate as measured by electromyography; 4. effect upon visual acuity; 5. tear production. Both a positive control (acetic acid) and a negative control (air) were employed. Baseline responses for each of the assessment parameters were determined under pre-exposure conditions (“zero-time controls”) and upon exposure to the negative control (“air-only controls”) for the prescribed period. A positive irritation response was based on three criteria: 1. the average response must be quantitatively greater than the pre-exposure response; 2. the average response must be greater than pre-exposure and greater than could be expected statistically from individual to individual differences within the group; 3. the average treated response must be greater than the air-only group’s response and greater than could be expected from individual differences observed within the group.

Concerning the ethical conduct of this study, informed consent was asserted in the odor threshold study but not mentioned in the eye irritation study; copies of the actual informed consent forms are not provided in the study report. The study also asserts approval through an ethical review but provides no documentation to support the statement. A detailed consideration of the ethical conduct of this study is provided in a separate memo by J. Carley (1/23/04). The odor threshold was determined to be 1.7 ppm (5 mg/m3). Conclusions from the eye irritation portion of the study include:

• For a one-minute exposure, the NOAEL for eye irritation is 3.3 ppm due to a lack of response in any parameter tested.

• For exposures 4-14 minutes, the NOAEL for eye irritation is 0.6 ppm based on responses on the Likert subjective scale at 1.9 ppm.

• For exposures of 1-8 hours, based on the statistically significant subjective (Likert scale) responses at 0.8 ppm MITC at 1-4 hours and the statistically significant eyeblink responses at 2 and 3 hours, 0.22 ppm was designated as the NOAEL for this study