Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 15 (2013) / Chapter Skim
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6 Methyl Isothiocyanate Acute Exposure Guideline Levels
6 Methyl Isothiocyanate Acute Exposure Guideline Levels
Pages 166-199
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From page 166... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 167... ...
Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL. SUMMARY Methyl isothiocyanate (MITC)
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From page 168... ...
. Upon dilution with water, metam sodium decomposes to MITC which evolves as a gas of hydrogen sulfide and lesser amounts of methylamine and carbon disulfide.
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From page 169... ...
HUMAN TOXICITY DATA 2.1. Odor Threshold and Odor Awareness MITC has a pungent horseradish-like odor at room temperature (Nihon Schering 1990)
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From page 170... ...
Exposures were most likely to a mixture of metam sodium hydrolysis products which include MITC, hydrogen sulfide gas, methylamine, and carbon disulfide. Among a group of 197 persons referred for health evaluation, 20 were identified as having persistent irritant-induced asthma and 10 were identified as having persistent exacerbation of pre-existing asthma.
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From page 171... ...
of metam sodium near a rural community in California. Several hours after application of 25,000 pounds of metam sodium to a 100-acre field, 250 nearby residents experienced ocular and upper-respiratory irritation, non-specific systemic symptoms, and lower-respiratory-tract complaints.
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From page 172... ...
No additional details of the methods were available. Subjective irritation was measured on a Likert scale in which irritation was rated from no irritation to a feeling the subject would like to end the exposure; the mid-point was described as similar to that of cutting a single mild onion.
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From page 173... ...
LOEL (ppm) Description 1 min 3.3 – 4 min 0.60 1.9 Subjective ocular irritationb 14 min 0.60 1.9 Subjective ocular irritation 1h 0.23 0.8 Subjective ocular irritation 1.5 h 0.22 – 2h 0.23 0.8 Subjective ocular irritation, increased blink rate.
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From page 174... ...
for 1 min, 0.6 ppm for 14 min, or 0.22-0.23 ppm for 1-8 h. When exposed at 1.9 ppm for 14 min or at 0.8 ppm for 1-8 h, subjects reported ocular irritation slightly less than that associated with cutting a single mild onion.
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From page 175... ...
Clinical signs noted during exposure included closure of the eyes, lacrimation, and peripheral vasodilation in all rats and a hunched posture in the majority of the animals. Peripheral vasodilation persisted for several hours after exposure.
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From page 176... ...
The no-observed-adverse-effect level was 1.7 ppm. TABLE 6-4 Acute Lethality Data on Methyl Isothiocyanate Concentration Exposure Species (ppm)
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From page 177... ...
Oral administration (gavage, water vehicle) of metam sodium to female B6C3F1 mice at 300 mg/kg for 10 or 14 days decreased thymus weight, increased spleen weight, increased bone marrow cellularity, reduced mature lymphocyte subpopulations in the thymus, depleted major subpopulations of thymocytes, and reduced body weight (Pruett et al.
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From page 178... ...
gavage, starting at 28 days mg/kg; no reproductive or 1978 of age until litters delivered, developmental effects; three-generations stomach lesions in dams. Reproductive Toxicity Rat 1, 5, or 25 mg/kg by gavage, Fetal growth retardation at 25 Irvine 1983 GDs 6-15 mg/kg, secondary to decreases in maternal food intake and body weight.
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From page 179... ...
Fetal growth retardation in the 25-mg/kg group was associated with decreased maternal food intake and reduced weight gain. Similar to the above study, mated Wistar rats were administered MITC (in corn oil)
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From page 180... ...
There was no consistent evidence of mutagenicity in any of these studies. MITC failed to induce sister chromatid exchanges in cultured Chinese hamster V79 cells, but gave positive results at some time points in an in vitro chromosome aberration test in the same system.
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From page 181... ...
In repeated exposure studies, no clinical signs were observed in rats exposed to MITC at 1 or 1.7 ppm (Rosskamp et al. 1978; Klimisch 1987)
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From page 182... ...
4.2. Mechanism of Toxicity Clinical signs and respiratory tract pathology consistent with the actions of a primary irritant have been observed in laboratory studies with rodents.
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From page 183... ...
4.4.4. Concurrent Exposure Issues MITC is a decomposition product of metam sodium, which can also yield other breakdown products including hydrogen sulfide, methyl isocyante, carbon disulfide, and methyl amine, depending on the soil pH and environmental conditions (O'Malley et al.
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From page 184... ...
The 0.8-ppm value is supported by no-effect concentrations in repeated-exposure studies with rodents. No signs of ocular irritation or other clinical signs were observed in rats exposed
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From page 185... ...
In repeated exposure studies, rats exposed to MITC at 6.8 ppm for 6 h/day, 5 days/week for 28 days showed signs of ocular irritation and general discomfort during daily exposure periods, beginning on the third exposure day and continuing throughout the study (Klimisch 1987)
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From page 186... ...
. Interspecies and intraspecies uncertainty factors of 3 each are usually applied to chemicals that are direct-acting irritants TABLE 6-8 AEGL-2 Values for Methyl Isothiocyanate 10 min 30 min 1h 4h 8h 21 ppm 21 ppm 17 ppm 10 ppm 5.3 ppm (63 mg/m3)
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TABLE 6-9 AEGL-3 Values for Methyl Isothiocyanate 10 min 30 min 1h 4h 8h 63 ppm 63 ppm 50 ppm 31 ppm 16 ppm (190 mg/m3)
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From page 188... ...
2011. Metam sodium intoxication: The specific role of degradation products - methyl isothiocyanate and carbon disulphide - as a function of exposure.
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From page 189... ...
Rush (1996) Methyl Isothiocyanate: Determination of Human Olfactory Detection Threshold and Human No Observable Effect Level for Eye Irritation.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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From page 191... ...
1996. Methyl Isothiocyanate: Determination of Human Olfac tory Detection Threshold and Human No Observable Effect Level for Eye Irritation.
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From page 192... ...
of distinct odor detection (I = 3) is derived using the Fechner function: I = kw × log (C ÷ OT50)
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From page 193... ...
1996. Methyl Isothiocyanate: Determination of Human Olfactory Detection Threshold and Human No Observable Effect Level for Eye Irritation.
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From page 194... ...
1981. Methyl Isothiocyanate: Acute Inhalation Toxicity in Rats.
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From page 195... ...
Methyl Isothiocyanate 195 Modifying factor: None Calculations: 10-min AEGL-3: Set equal to 30-min AEGL-3 = 63 ppm 30-min AEGL-3: C3 × 30 min = 7.383 × 106 ppm-min C = 63 ppm 1-h AEGL-3: C3 × 60 min = 7.383 × 106 ppm-min C = 50 ppm 4-h AEGL-3: C = 94 ppm ÷ 3 C = 31 ppm 8-h AEGL-3: C1 × 480 min = 7,520 ppm-min C = 16 ppm
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From page 196... ...
1996. Methyl Isothiocyanate: Determination of Human Olfactory Detection Threshold and Human No Observable Effect Level for Eye Irritation.
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From page 197... ...
1981. Methyl Isothiocyanate: Acute Inhalation Toxicity in Rats.
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From page 198... ...
198 Accute Exposure Guideline Levels AP PPENDIX D CATEGOR RY PLOT FOR R METHYL IISOTHIOCYA ANATE FIGUR RE D-1 Categorry plot of animaal and human ddata and AEGL values for methhyl isothioccyanate. TABLE E D-1 Data Ussed in the Category Plot for M Methyl Isothioccyanate Source Species S ppm Minutes Categgory Commentss AEGL-1 0.27 10 AEGGL AEGL-1 0.27 30 AEG GL AEGL-1 0.27 60 AEG GL AEGL-1 0.27 240 AEG GL AEGL-1 0.27 480 AEG GL AEGL-2 21 10 AEG GL AEGL-2 21 30 AEG GL AEGL-2 17 60 AEG GL AEGL-2 10 240 AEG GL AEGL-2 5.3 480 AEG GL AEGL-3 63 10 AEG GL AEGL-3 63 30 AEG GL AEGL-3 50 60 AEG GL (Continueed)
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From page 199... ...
a Note: the discomfort associated with human exposure at 0.8 ppm (Russell and Rush 1996) was below the threshold for notable discomfort that constitutes an AEGL-1 effect.
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