2-hydroxy-2-methylpropionitrile

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - workers

Acute Exposure guideline levels (AEGLs) have been established and reported by the AEGL-Committee (US-NAC, Actone Cyanohydrin, Interim Acute Exposure Guideline Levels (AEGLs), Interim final draft, 2005).

See section general population below.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

AEGLs:

Acute Exposure guideline levels (AEGLs) have been established and reported by the AEGL-Committee (US-NAC, Actone Cyanohydrin, Interim Acute Exposure Guideline Levels (AEGLs), Interim final draft, 2005). The following part is cited from this report:

“AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes to 8 hours. AEGL-2 and AEGL-3 levels, and AEGL-1 levels as appropriate, will be developed for each of five exposure periods (10 and 30 minutes, 1 hour, 4 hours, and 8 hours) and will be distinguished by varying degrees of severity of toxic effects. It is believed that the recommended exposure levels are applicable to the general population including infants and children, and other individuals who may be sensitive or susceptible. The three AEGLs have been defined as follows:

AEGL-1 is the airborne concentration (expressed as ppm or mg/m³) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, non-sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.

AEGL-2 is the airborne concentration (expressed as ppm or mg/m³) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects, or an impaired ability to escape.

AEGL-3 is the airborne concentration (expressed as ppm or mg/m³) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.

 

Summary Table of AEGL values for Acetone Cyanohydrin^ab
Classification	10-Minute	30-Minute	1-Hour	4-Hour	8-Hour	Endpoint (Reference)
AEGL-1 (Non-disabling)	2.5 ppm (8.8 mg/m³)	2.5 ppm (8.8 mg/m³)	2.0 ppm (7.0 mg/m³)	1.3 ppm (4.6 mg/m³)	1.0 ppm (3.5 mg/m³)	application of AEGL-1 values for hydrogen cyanide
AEGL-2 (Disabling)	17 ppm (60 mg/m³)	10 ppm (35 mg/m³)	7.1 ppm (25 mg/m³)	3.5 ppm (12 mg/m³)	2.5 ppm (8.8 mg/m³)	application of AEGL-2 values for hydrogen cyanide
AEGL-3 (Lethal)	27 ppm (95 mg/m³)	21 ppm (74 mg/m³)	15 ppm (53 mg/m³)	8.6 ppm (30 mg/m³)	6.6 ppm (23 mg/m³)	application of AEGL-3 values for hydrogen cyanide

a.       Acetone cyanohydrin decomposes spontaneously in the presence of water to yield hydrogen cyanide and acetone. Therefore, always a mixed cyanide and cyanohydrin exposure will result from acetone cyanohydrin release. The derived values refer to the sum of acetone cyanohydrin and hydrogen cyanide. Therefore, both acetone cyanohydrin and hydrogen cyanide concentrations should be measured and considered.

b.      Cutaneous absorption may occur; direct skin contact with the liquid should be avoided.

The derivation of AEGL-1 values was based upon the facts that acetone cyanohydrin decomposes spontaneously to hydrogen cyanide and acetone and that both local and systemic toxic effects of acetone cyanohydrin are due to free cyanide. Once absorbed, a dose of acetone cyanohydrin behaves in a manner identical to that of its molar equivalent in absorbed free cyanide. It is appropriate to apply the AEGL-1 values (on a ppm basis) derived for hydrogen cyanide (NRC, 2002) to acetone cyanohydrin. This procedure is supported by the fact that similar values would be derived on the basis of available acetone cyanohydrin studies in rats (derivation basis would be exposure to 9.2 ppm for 6 hours/day, 5 days/week for 4 weeks, which did not result in red nasal discharge; Monsanto, 1986a) using a total uncertainty factor of 10.

The odor threshold of acetone cyanohydrin has not been firmly established. Shkodich (1966 published the odor threshold for acetone cyanohydrin in water (0.06 mg/l). However, the odor would necessarily be the consequence of a mixed presentation of the HCN and acetone cyanohydrin levels in air. Since no definitive reports on the odor threshold of acetone cyanohydrin were located in the literature, no level of distinct odor awareness (LOA) was derived.

The derivation of AEGL-2 values was based upon the facts that acetone cyanohydrin decomposes spontaneously to hydrogen cyanide and acetone and that the systemic toxicity of acetone cyanohydrin is due to free cyanide. Once absorbed, a dose of acetone cyanohydrin behaves in a manner identical to that of its molar equivalent in absorbed free cyanide. It is appropriate to apply the AEGL-2 values (on a ppm basis) derived for hydrogen cyanide (NRC, 2002) to acetone cyanohydrin. This procedure is supported by the fact that similar values would be derived on the basis of available acetone cyanohydrin studies in rats (derivation basis would be exposure to 29.9 ppm for 6 hours/day, 5 days/week for 4 weeks, which caused signs of irritation, while the next higher concentration produced respiratory distress, prostration, convulsions and tremors; Monsanto, 1986a) using a total uncertainty factor of 10. The derivation of AEGL-3 values was based upon the facts that acetone cyanohydrin decomposes spontaneously to hydrogen cyanide and acetone and that the systemic toxicity of acetone cyanohydrin is due to free cyanide. Once absorbed, a dose of acetone cyanohydrin behaves in a manner identical to that of its molar equivalent in absorbed free cyanide. It is appropriate to apply the

AEGL-3 values (on a ppm basis) derived for hydrogen cyanide (NRC, 2002) to acetone cyanohydrin. This procedure is supported by the close similarity of acetone cyanohydrin and hydrogen cyanide regarding death in rats: Blank (1983) reported that 3 of 10 rats died after the first exposure to 68 ppm hydrogen cyanide, while the subsequent two exposures on the following days caused no additional deaths. This finding closely resembles that of Monsanto (1986a) reporting death of 3 of 20 animals after the first exposure to 60 ppm acetone cyanohydrin (the actual exposure concentration on the first day might have been slightly higher than the average 59.6 ppm), while no additional deaths were found in the 19 subsequent exposures.”