Cyclohexane

• [General Manufacturing Information] Pharmaceutical and Medicine Manufacturing
• [General Manufacturing Information] Plastics Material and Resin Manufacturing
• [General Manufacturing Information] Synthetic Rubber Manufacturing

Toxicity Summary: IDENTIFICATION AND USE: Cyclohexane is a colorless, highly flammable liquid occurring naturally in petroleum at concentrations of 0.5-1.0%. It has a pungent petroleum-like odor and is used as an organic solvent for lacquers, resins, and synthetic rubber; paint and varnish remover; extraction of essential oils; manufacturing of solid fuel for camp stoves; in fungicidal formulations; in recrystallization of steroids; and in analytical chemistry for molecular weight determinations. It is also a chemical intermediate in the manufacturing of adipic acid, benzene, cyclohexyl chloride, nitrocyclohexane, cyclohexanol and cyclohexanone. Not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Studies from the exposure of the general population to cyclohexane revealed that human milk from five of eight mothers contained cyclohexane (concentrations not determined) from the mothers' exposure to environmental pollutants since they resided near chemical manufacturing plants or industrial user facilities. HUMAN EXPOSURE AND TOXICITY: The available data indicate that cyclohexane can be absorbed via oral and inhalation routes but no adequate data exist via the dermal route. Potential symptoms of overexposure to cyclohexane are irritation of eyes, skin and respiratory system; drowsiness; dermatitis; narcosis and coma although cyclohexane generally has low acute toxicity. In humans exposed via inhalation for 4 hours to 86 or 860 mg/cu m cyclohexane, there were no significant treatment-related effects. Occupational exposure to 5 to 211 ppm cyclohexane for a median of 1.2 years, had no adverse effects on the peripheral nervous system. There have been no systemic poisonings reported in man. Cyclohexane is known to undergo oxidative metabolism to yield cyclohexanol (major metabolite), cyclohexanone, and possibly other oxidative products (1,2- or 1,4-dihydroxycyclohexane and its corresponding ketone analogs). ANIMAL STUDIES: High vapor concentrations have produced convulsions in rabbits. Toxic oral doses in rabbits led to severe diarrhea, circulatory collapse and death, without prominent central nervous depression or anesthesia. Autopsy revealed generalized vascular damage but no effects on blood formation. Rats and mice, were exposed to 0, 500, 2000, or 7000 ppm of cyclohexane vapor 6 hr/day, 5 days/week for 14 weeks. During exposure sessions, mice exposed to 7000 ppm exhibited clinical signs of toxicity which included hyperactivity, circling, jumping/hopping, excessive grooming, kicking of rear legs, standing on front legs, and occasional flipping behavior. In another study, male and female mice exposed to 7000 ppm had slight increases in measures of circulating erythrocyte mass (red blood cells, hemoglobin, hematocrit) and plasma protein concentration (males only). Male rats and male and female mice exposed to 7000 ppm had significantly increased relative liver weights, and 7000 ppm male mice also had significantly increased absolute liver weights at the end of the exposure period. In the third study, female rats were administered cyclohexane intraperitoneally at a dose of 0.375, 0.75, or 1.5 g/kg, 5 days a week for 2 weeks. The high dose of 1.5 g/kg of cyclohexane caused a proximal tubular dysfunction of the kidney which resulted in an increase in beta-2-microglobulin. The increase in beta-2-microglobulin was attributed to the metabolite cyclohexanol. When testing the effect of cyclohexane on reproduction and development, there were statistically significant reductions in mean body weight, overall mean body weight gain, and overall mean food efficiency for P1 and F1 females exposed to 7000 ppm. Adult rats exposed to 2000 ppm or 7000 ppm cyclohexane exhibited diminished response or no response to a sound stimulus while in the chambers during exposure. Mean pup weight was statistically significantly reduced from lactation day 7 throughout the remainder of the 25-day lactation period for both F1 and F2 7000 ppm litters. Cyclohexane was negative for mutagenicity at doses of 0.01, 0.033, 0.10, 0.33, 1.0, 3.3, and 10 mg/plate in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) with or without metabolic activation. ECOTOXICITY STUDIES: Cyclohexane inhibited growth of Chlorella for 11-13 days, but prolonged the exponential growth phase and increased the growth yield 2.5 fold compared with the control. Acute toxicities after 24 and 96 hr exposures to seven alicyclic hexanes including cyclohexane were determined for striped bass and one of their major food organisms, the bay shrimp, Crangon franciscorum. The 96 hr LC50 for striped bass and bay shrimp ranged from 3.2 to 9.3 uL/L and from 1.0 to 6.2 uL/L, respectively.

Toxicity Data:

• [Toxicity Data] LCLo (mice) = 70,000 mg/m3/2H
• [Toxicity Data] LD50: 1.30 g/kg (Oral, Mouse) (T21)
• [Environmental Toxicity] The substance is very toxic to aquatic organisms. The substance may cause long-term effects in the aquatic environment. It is strongly advised not to let the chemical enter into the environment.