NAPA -20° WASH

SECTION 2: Hazards identification

EMERGENCY OVERVIEW Slight odor. May be fatal if swallowed. Vapors can cause eye irritation. LDSO Rat (Oral: 3628 mg/kg (100% methanol concentration) LDS Rabbit (Skin): 20 mi/kg (100% methanol concentration) Carcinogency: No National Toxicology Program: No International Agency for Research on Cancer: No

Health hazards

Acute and Chronic) Acute: Acute methanol intoxication is manifested initially by signs of narcosis. This is followed by a latent period in which formic acid accumulates in the body causing metabolic acidosis. Severe abdominal, leg, and back pain occur and visual degeneration can lead to blindness. 1. Humans — Ingestion of 80 to [50 mL of methanol is usually fatal to humans (HSDB 1994). One worker died from exposure to vapor ranging from 4,000 to 13,000 ppm over 12 hours (ACGIH 1991). The concentration of 4,000 ppm is roughly equivalent to a total of 1,140 mg/kg over the 12-hour period (see end note 2). Poisoning by nonlethal doses can be described in three stages: (1) narcotic stage similar to ethanol; (2) latent period of 10-15 hours; (3) visual disturbances and central nervous system lesions (Rowe and McCollister 1981). Visual disturbances can lead to blindness due to edema of the retina and atrophy of the optic nerve head (HSDB 1994). Third-stage CNS lesions include headache, dizziness, abdominal, back, and ieg pain, delirrum that can lead to coma, and nausea CHSDB 1994). Formic acid production causes severe metabolic acidosis (Rowe and McCollister 1981). BO Animals — Oral LDSO values for methanol is animals are 0.4 g/kg in the mouse, 6.2 to [3 g/kg in the rat, 14.4 g/kg in the rabbit, and 2 to 7 g/kg in the monkey (Rowe and McCollister 1981). The LD50 for dermal application to rabbits is 20 mL/kg (approximately !6 g/kg) (Rowe and McCollister 1981). Dose-response data for inhalation vary with species, dose, and duration (8.800 ppm for 8 hours to 152.800 ppm for 94 minutes), Symptoms of intoxication include incoordination, salivation, lethargy, narcosis, and death (Rowe and McCollister 1981). Subchronic/Chronic: Chronic exposure to methanol, either orally or by inhalation, causes headache, insomnia, gastrointestinal problems, and blindness in humans and hepatic and brain alterations in animals. EPA has derived an oral RfD (reference dose) (see end note 3) for methanol of 0.5 mg/kg/day, based on the absence of liver and brain effects in animals exposed by mouth to 500 mg/kg/day. |. Humans ~ “Chronic” exposure to methanol vapors (no time or dose given) caused conjunctivitis, headache, giddiness, insomnia, gastric disturbances, and bilateral blindness (ACGIH 1991}. Marked vision loss oecurred in one worker exposed to 1,200 to 8,000 ppm vapor for 4 years (ACGIH L991}. 2. Animals ~ No effects were seen in rats given 1% (approximately 140 mg/kg/day) methanol in drinking water for 6 months (Rowe and McCollister 1981}. Hepatic abnormalities (proteinic degeneration, altered RNA metabolism) occurred in rhesus monkeys given 3 to 6 g/kg for 3 to 20 weeks and in rats given 10, 100, or 500 mg/kg/day for one month (Rowe and McCollister 1981), Rabbits chronically fed methanol (no dose or time given) had increasing blood levels, brain and eye edema, and myelin thinning (HSDB 1994). Male and female rats were gavaged with 100, 500, or 2,500 mg/kg/day for 90 days (U.S. EPA 1994). Increased levels of SGPT and SAP as well as decreased brain weights were seen in both sexes at the highest dose; a no-observed-adverse effect level (NOAEL) for the study was 500 mg/ke/day. Based on these data, the U.S. EPA (1994) calculated a chronic RED (see end note 4) for methanol of O.S mg/kg/day. No toxic NAPA Wash —20 bho effects were seen in dogs exposed by inhalation to either [0,000 ppm for 3 minutes, 3x/day, for [00 days or to 450 or 500 ppm, 8 hours/day for 379 days (Rowe and McCollister 1981). Ultrastructural changes were observed in the photoreceptor cells of rabbits exposed to 46.6 ppm for 6 months (Rowe and McCollister [981}. Rowe and McCollister (1981) concluded that the effects of combined oral and inhalation exposure appear to be additive. Rats exposed by inhalation to 16.8 ppm, 4 hours/day, for 6 months and administered 0.7 mg/kg/day orally had changes in blood morphology, oxidation-reduction processes, and liver function (Rowe and McCollister 1981). Carcinogenicity: No information was found on the carcinogenicity of methanol in the secondary sources searched. {. Humans ~ No information was found in the secondary sources searched concerning the carcinogenicity of methanol to humans. 2. Animals - No information was found in the secondary sources searched concerning the carcinogenicity of methanol to animals. The NTP has assigned a project leader for methanol and the design of the study is in progress (NTP 1994).