Butan-1-ol

Endpoint summary

Description of key information

In humans, Butan-1-ol is slightly to moderately irritant to the skin on prolonged contact, and moderately irritant to the eyes. In addition, local irritation of the respiratory tract was observed as well as signs of drowsiness and dizziness at high concentrations.

 

One poorly documented report describing neurological effects and hearing loss in workers exposed to Butan-1-ol has not been substantiated by later ones which did not report these effects in humans. Thus, there is no evidence for a permanent damage of hearing capability in the sense of ototoxicity as well as for adverse and/or persistent neurological impairments in humans. This is supported by valid studies in experimental animals.

Additional information

In a controlled acute exposure study, sixteen subjects were exposed (i.e. eye only) to Butan-1-ol at concentrations of 0, 0.300, 0.900 and 3.0 mg/L (990ppm) for a daily sequence of 15 min, 60 min and again 15 min expositions on 5 different days. During the 60 min run, a slight increase in perceived sensory eye irritation intensity for all exposure concentrations was observed. The threshold for irritation (conjunctival hyperemia) was never clearly exceeded (Hempel-Joergensen et al., 1999).

 

In an acute human exposure experiment regarding the sensory irritation potential, each subject was tested on four levels of Butan-1-ol in increasing concentrations in the range between 1.5 – 12.0 mg/L. The right or left eye was chosen randomly to be exposed to Butan-1-ol for 2 min intervals, the opposite eye was chosen to be exposed to the reference gas CO₂. In addition, whole body exposure was performed in closed chambers using concentrations of 0, 0.0025, 0.005, and 0.010 mg/L for 1.5 hours. Statistically significant association between exposure concentration, general sensory irritation, sensory eye irritation, sensory throat irritation, sensory odor irritation, sensory nose irritation was observed (Kjaerguard et al., 1997).

 

Spray painters exposed to solvents were compared to non-exposed workers regarding possible neurotoxic effects. The exposed group consisted of 83 spray painters with at least 10 years' working experience and controls of 42 workers without any relevant occupational contact with solvents. Four sites out of the workplaces reported Butan-1-ol measurements (5.7, 1.5, 5.4, and >300 mg/m3), but co-exposure to other solvents was reported at these workplaces. The questionnaire regarding smoking, drinking habits and medication showed no statistically significant differences between the two groups. Biological monitoring revealed no significant differences in results between spray painters and controls except in regards to hippuric and methylhippuric acid in urine. With regards to neurological parameters, clearly no increase in loss of memory, no difficulties in concentration, no increased tiredness and no frequent headache was observed (Triebig et al., 1992).

 

The hearing capability of 11 men, who had been exposed to Butan-1-ol during the manufacture of cellulose acetate ribbon and who were without the benefit of personal protective equipment from noise, was investigated. The authors reported that nine of the men experienced hearing loss in direct relation to exposure duration, when compared with 23 individuals of a control group and 47 workers exposed to 90 to 100 dB of industrial noise alone. The average hearing loss of the Butan-1-ol-exposed group in the central frequencies (500 - 3,000 Hz) was not large, 21.94 dB (range 11.59 - 32.39 dB), with a mean widening of the break between 3,000 and 4,000 Hz of 42.22 dB. The average hearing loss tended to decrease as the frequencies moved away from the central zone. However, the audiologic procedures and industrial hygiene methods used were possibly not adequate (horizontal and vertical axes were mislabeled on various charts, audiograms were misinterpreted, calibration problems had existed and subjects were not screened correctly). Thus, care should be taken in drawing firm conclusions from the report (Velazquez et al, 1969).

 

Subjects with Multiple Chemical Sensitivity (MCS) were exposed to Butan-1-ol at low concentrations and cytokine/chemokine profile in airway epithelial lining fluid was investigated. Eighteen patients were exposed to Butan-1-ol while seated in an exposure chamber for 50 min. The exposure concentration of Butan-1-ol was 0.0115 mg/L (3.7 ppm). MCS subjects and healthy controls showed similar upper airway inflammatory mediator profiles at baseline. Direct comparison of mediator levels in the MCS group and controls after Butan-1-ol exposure revealed no significant group differences (Dantoft et al., 2015)

 

When 105 patients were tested for immunological contact urticaria, no redness in combination with edema was observed in any subject. Four patients were positive for redness only (Lahti et al. 1980).

 

The skin irritation in humans was explanatively studied via the Cutaneous blood flow values (CBFV), which were determined by laser Doppler flowmetry before and after patch application. Two series of experiment were done. First study: undiluted test substance, 8 volunteers, 48 h exposure period, CBFV were measured 12 h later. Second experiment: 10% solution (in water), 4 volunteers, 3 h exposure period CBFV were measured 1 h, 24, 48 and 73 h after removal of the patch. Additionally, the rabbit skin erythema scores and the uridine uptake inhibition test on KB cells were conducted for comparison. The CBFV in human correlated very well with erythema scores obtained on rabbits, a poor correlation was observed between the in vitro and in vivo results (Jacobs et al., 1989).

 

Information on the effects of Butan-1-ol in humans from oral exposure is limited to one case report from a suicide attempt, where neurological, gastrointestinal, and cardiovascular symptoms were noted. The solvent was an unknown dose of 1 -Butan-1-ol. The patient totally recovered after supportive therapy over 30 h (Bunc et al., 2006).

 

During controlled experiments on the kinetics and metabolism of Butan-1-ol, human volunteers tolerated exposure inhalation to levels of up to 200 ppm (0.62 mg/L) for 2 hours without signs of discomfort (Astrand et al., 1976).

 

Within toxicokinetics investigations and PBPK modeling respiratory bioavailability and other TK parameters were investigated (for details see section Toxicokinetics). Within these investigations, no clinically adverse effects were reported (Teeguarden et al., 2005).

 

The physical condition of approximately 100 male workers exposed to Butan-1-ol during the coating and drying of photographic paper was followed for 10 years. At the beginning of the study, when the average concentration of Butan-1-ol in the workplace was 200 ppm (0.620 mg/L), the mean erythrocyte count was slightly decreased. When the average concentration was reduced to 100 ppm (0.310 mg/L), no systemic effects were observed, and there were no changes in clinical chemistry or chest X-ray parameters that could be associated with occupational Butan-1-ol exposure. Corneal inflammation was occasionally observed in workers exposed to concentrations of Butan-1-ol of 200 ppm (0.620 mg/L) or more. When the average concentration was reduced to 100 ppm (0.310 mg/L) complaints of eye irritation or unpleasant odour were rare (Sterner et al, 1949).

 

Controlled chamber studies with 10 male and female volunteers, exposed to Butan-1-ol for 3 to 5 minutes experienced objectionable nose and throat sensory irritation at 25 ppm (77 mg/m3) and in addition sensory ocular irritation at 50 ppm (154 mg/m3, Nelsonet al, 1943).

 

When exposure related observations in humans were performed, a mean blood level of 0.45 mg Butan-1-ol/L (maximum 1.288 mg/L) was reported, at the end of the work shift, in 9 healthy parquet workers (25 - 58 years of age) occupationally exposed to mixtures of organic solvent vapours containing Butan-1-ol. The average measured concentration was 66.7 mg Butan-1-ol/m3 (21.6 ppm), with peaks up to 1200 mg/m3 (400 ppm, Denkhauset al, 1986).

 

Urine samples were collected from 11 male printers, working in two small shops, exposed to mixed solvent vapours. At the end of the 8-hour work shift, there was a significant increase in total Butan-1-ol concentration (228 ± 62 ng/mg creatinine) in the urine of exposed workers when compared to controls (12 ± 9 ng Butan-1-ol/mg creatinine; Kawai et al. 1997).