Table 1 Work-related olfactory dysfunction: Human studies (in chronological order)

^aFriberg 1950 [29]

Battery factory

3–15 Cd

10–150 Ni

43 (group 1: longer employment 9–34 years)

15 (group 2: shorter employment 1–4 years)

–

Test with odour samples (coffee, perfume, peppermint and petrol)

Group 1: 37% impaired sense of smell (32.6%: anosmia).

Group 2: 6.7% (one case) partially impaired sense of smell.

^aBaader 1951 [30])

Battery factory

N. i.

8

–

Test with odour samples (no further details)

4 hyposmic or anosmic.

^aPotts 1965 [31]

Battery factory

Cd dust and fumes: 0.6–236 (1949)

< 0.5 (1950)

< 0.1 (1956)

70

–

N. i.

64% anosmic.

^aLiu et al. 1985 [32]

Cadmium smelters

Cd oxide: 0.004–0.187

65

–

N. i.

21.5% anosmic.

^aAdams and Crabtree 1961 [33]

Battery factory

Cd: 0.028–2.76

Ni: 0.0016–0.056

106

84

Threshold test with phenol

27.3% anosmic (Co: 4.8% anosmic)

^aRose et al. 1992 [34]

Factory producing refrigerating coils

Cd fumes up to 0.3

55

16

Threshold test with n-butanol.

Identification test with 10 different olfactory stimuli

13% severe hyposmia (Co: 0%), 44% weakly hyposmic (Co: 31%).

Identification test: no significant difference.

^aRydzewski et al. 1998 [35]

^aSulkowski et al. 2000 [36]

Battery factory

Atmospheric cadmium concentrations: 0.05–2.1

73

43 forestry workers

Threshold identification test with modified Elsberg-Levys method

Significantly impaired ability to detect and identify odours.

Overall result: 26% hyposmia, 17.8% parosmia, 1.4% anosmia (Co: 30.2% parosmia, 69.8 normosmia).

^aMascagni et al. 2003 [37]

Workers in a cadmium foundry and sintering plant

Cadmium concentrations (max.): 1.530 (1975) -0.0171 (1995); by 1978, the measurement results had already dropped substantially below 1 (at 0.207)

33

39 drivers and storekeepers, 23 welders

Threshold test with phenyl ethyl alcohol

Identification test with Wright’s confusion matrices

Olfactory threshold significantly higher in Cd workers than in controls.

Identification test: no significant difference (a non-significant impairment in cadmium workers).

Overall results:

3.1% anosmic, 3.1% severely hyposmic, 24.1% mildly/moderately hyposmic (welders: 0% anosmic, 4.3% severely hyposmic, 8.7% mildly/moderately hyposmic; Co: 0% anosmic, 0% severely hyposmic, 7.7% mildly/moderately hyposmic).

^a2 studies from USSR cited in Sunderman [28]: (Tatarskaya 1960)

(Kucharin 1970)

Electrolytic Ni refinery

Electrolytic Ni refinery

N. i.

N. i.

N. i.

458

N. i.

N. i.

N. i.

N. i.

Frequent olfactory impairment, atrophic nasal mucosa, nasal septal ulceration and sinusitis.

Anosmia in 114/251 workers (46%) with chronic sinusitis; less severe loss of smell in other Ni-exposed workers.

Seeber et al. 1976 [53]

Chrome paint plant (manufacture of basic zinc chromate (zinc yellow))

Values exceeded 0.1 CrO₃ air, and rose at certain points to up to 20 CrO₃. More precise values are not stated.

5 chronically exposed workers, 14 intermittently exposed workers (not longer than 2 h per day), 5 mask-wearing workers (wearing fine-dust filter masks for the full duration)

9 office workers at the same company, 23 employees at hospital

Test with odour strips (6 different stimuli in 8 concentrations)

Olfactory sensitivity of control group and non-exposed individuals substantially higher than that of exposed individuals.

“Significant” relationship between chromium exposure and loss of olfaction.

Chronically exposed individuals: damage to the nasal mucous membrane.

Intermittently exposed group and workers with a mask: damage to the nasal mucous membrane only in a part.

Seeber and Fikentscher 1980 [54]

See above

Occupational exposure “substantially reduced” by suitable measures (not specified)

3 chronically exposed workers, 9 intermittently exposed workers (not longer than 2 h per day)

4 mask-wearing workers (wearing fine-dust filter masks for the full duration)

7 office workers at the same company,

23 employees at hospital

See above

Confirmation of the relationship between the pathological nasal mucous membrane findings and olfactory dysfunction in 16 workers exposed to different levels.

No improvement in the mucous membrane or olfaction.

^aWatanabe and Fukuchi (1981) [55]

Chromate production plant

Air Cr concentration of 20.17 according to [56]

33

–

T&T olfactometer (odour detection threshold and odour recognition)

“Middle and high grade decrease of odor recognition faculty” in 18 workers (54.5%) including 2 anosmiac, one of whom also complained of a taste disorder.

51% exhibited nasal septum perforations.

Relation between degree of olfaction loss and duration of employment in the chromate producing factory.

^aKitamura et al. 2003 [56]

Cr plating factory

Average atmospheric concentration was 0.0228

27

34

T&T olfactometer (odour detection threshold and odour recognition)

Olfactory perception threshold test

No significant differences for sensory and perception threshold.

Significantly higher values for the odour recognition test than those for controls, positive correlation with duration of exposure.

None of Cr workers showed nasal septum perforation or ulceration.

Aiyer et al. 2003

Chromium plating industry

N. i.

28

–

N. i.

11 workers anosmic (nasal septal perforation of different magnitudes on all exposed workers, majority with initial symptom of nasal irritation).

^aLucchini et al. 1997 [58]

Ferroalloy production plant

Manganese dust exposure: 0.026–0.750 (geometric mean: 0.193)

35

37

Olfactory perception threshold to PM-carbinol (3-methyl-1-phenylpentan-3-ol dilution series)

No significant differences (although it was negatively associated with Mn levels in urine in the exposed group)

^aMergler et al. 1994 [59]

Ferromanganese and silicomanganese alloy plant

Manganese dust exposure: 0.014–11.48

Total Mn levels in dust: 0.89 (geometric mean)

Manganese content of respirable dust fraction: 0.001 and 1.273 (geometric mean: 0.04)

74 (matched pairs)

74

Olfactory perception threshold to PM-carbinol

Significantly increased olfactory perception among workers compared to controls.

^aAntunes et al. 2007 [60] ^aBowler et al. 2007 [61]

San Francisco/Oakland Bay Bridge welders

Atmospheric manganese levels lay between 0.11 and 0.46 (55% > 0.20)

43 welders

43 (matched by age, sex, education and smoking status from the database of the University of Pennsylvania Smell and Taste Center)

UPSIT identification test

Significantly weaker olfactory function of welders than in controls.

Score of 88% of the workers below their individually matched controls.

3% of the welders were anosmic.

Better olfactory function in workers with the highest Mn blood levels than those with the lowest Mn blood levels.

Bowler et al. 2011 [62]

Follow-up study three and a half years later

–

26 welders from the San Francisco/Oakland Bay Bridge welder study (13 study participants were no longer working as welders)

–

UPSIT identification test

No significant differences from earlier findings.

The blood-manganese levels of the former workers were significantly lower than those of their colleagues.

Sen et al. 2011 [63]

Welders

Cumulative Mn exposure (mg/m³x years):

Welders 0.881 (± 0.567)

Controls 0.002 (± 0.0003)

7 welders

7

MRI

Increased manganese deposition in the olfactory bulb and in other regions of the brain.

No statistically significant differences in the olfactory test between the two groups (data not shown).

Guarneros et al. (2013)

Persons living in proximity to a manganese plant

Elevated manganese hair concentration (mean 0.00973 vs. 0.00101)

30 persons living within a one-kilometre radius of a Mexican manganese mine

30 controls living more than 50 km away

Sniffin’ Sticks olfactory test series (threshold, discrimination and identification tests)

Significantly diminished olfactory function in those living close to the manganese mine (in threshold, discrimination and identification tests).

Lucchini et al. 2012 [65]

Residents of Valcamonica: Italian region, marked by ferrous alloy plants until 2001

Average Mn atmospheric and soil values at the time of the study: 0.0495, 958

154 young people aged between 11 and 14

157 young people from Lake Garda region

Sniffin’ Sticks (identification test)

Significantly poorer olfactory function associated with Mn content in the soil.

Iannilli et al. 2016

Valcamonica (see above) and Bognolo Mella: regions with a history of high Mn contamination

–

9 young people from Valcamonica and Bagnolo Mella exposed to manganese

4 young people from the Lake Garda region

Sniffin’ Sticks (identification test),

fMRT (response activity to olfactory tasks)

No significantly different results of the identification test between the two groups.

Reduction in activity in relevant olfactory brain regions.

In comparison with a larger control group from a database, significant differences were observed with regard to the size of the olfactory bulb and in the olfactory test involving Sniffin’ Sticks.

Casjen et al. 2017 [67]

Blue collar workers

Median: 58.3 μg/m³ x years

(interquartile range 19–185 μg/m³ x years)

354

1031

Sniffin’ Sticks (identification test)

No relevant association of former Mn exposure at relatively low levels with impaired olfaction.

Pyatayev et al. 1971 [73]

Zinc production plant

Zinc oxide, zinc sulfate and metal dusts.

Co-exposure to further strongly corrosive and irritant substances

301

63

Olfactometer employing mint and dilute acetic acid

Significant elevations of sensory thresholds.

Elevations were highest among workers responsible for roasting the zinc ore.

Anonymous 1938, ^aTisdall et al. 1938 [74, 75]

(Treatment in special clinics with

zinc in nasal spray for prevention of poliomyelitis infection)

Nasal spray solution containing 1% zinc sulfate and 0.5% tetracaine

5233 children (4713 (received two sprayings) + 520 (received one spraying))

6300

N. i.

No more than a quarter exhibited temporary anosmia.

^aTisdall et al. 1938 [75]

(Patients treated by the same otolaryngologists, but in their private practices)

See above

5000 children and adults

–

N.i.

6 months following treatment: 44 of the patients were permanently anosmic (52 with disturbances of smell and taste).

Davidson et al. 2010 [76]

(Nasal Dysfunction Clinic of the University of California in San Diego)

Intranasal zinc gluconate gel

10 patients

–

n-Butanol threshold

UPSIT (identification test)

3 subjects with anosmia and 7 with hyposmia.

Alexander et al. 2006 [77]

(See above)

Intranasal zinc gluconate gel

17 patients

–

n-Butanol threshold,

identification test employing seven known odorants and one substance for testing the trigeminal function, UPSIT (9 patients)

Impaired olfaction in all patients: 7 patients anosmic, 10 hyposmic.

Trauma and infection were ruled out as causes of hyposmia and anosmia diagnosed in 15 of these patients in the relevant tests.

Jafek et al. 2004 [78]

(Special “Taste and Smell Center” at the University of Colorado School of Medicine)

Use of zinc gluconate gel

10 patients

–

N. i.

Suffering of severe hyposmia in conjunction with parosmia or anosmia following use of zinc gluconate gel.

^aCalvert et al. 1998 [102]

Structural fumigation workers

Lifetime duration of methyl bromide and sulfuryl fluoride exposure: 1.2 and 2.85 years

Sulfuryl fluoride values of earlier NIOSH measurements: below 20

123

120

UPSIT (identification test)

Significantly weaker olfactory function in workers with high sulfuryl fluoride exposure over the year preceding examination.

Quandt et al. 2016 [104]

Latino farmworkers

Lifetime exposure.

Total years in jobs involving pesticide exposure: farmworkers 13.11 (mean), non-farmworkers 3.84 (mean)

304

247

Sniffin’ Sticks Kit (identification test and threshold test with n-butanol)

No difference in odour identification performance but significantly higher odour thresholds.

^aHolmström and Wilhelmsson 1988 [111]

Workers at a chemical plant where formaldehyde and products based on formaldehyde were produced

0.05–0.5 formaldehyde (for the group of workers impregnating paper up to 1)

70

36 (office workers with 0.9 mean exposure to formaldehyde)

Sensory threshold test employing pyridine

Significantly reduced olfactory function.

^aHolmström and Wilhelmsson 1988 [111]

Work with glued wood in the production of furniture

0.2–0.3 (formaldehyde)

1–2 (wood dust)

100

36

See above

Significantly reduced olfactory function (but no difference between the formaldehyde and the formaldehyde-wood dust groups).

^aHisamitsu et al. 2011 [112]

Medical students during cadaver dissection

0.64–1.2 (middle of the laboratory), 0.28–0.88 (in the corners)

41

–

Nagashima jet nebulising olfaction test with bromine (detection threshold)

Significantly diminished olfactory function (32%, temporary).

Kilburn et al. 1985 [113]

Histology technicians

0.25–2.38 (exposure to other solvents such as xylene, toluene and also chloroform)

76

56

Questionnaire

Significantly more self-reported frequent reduced sense of smell in histology technicians

(32% of the women who were exposed to formaldehyde for 1 to 3 h and likewise 32% of the women who were exposed for over 4 h stated that their olfactory function was diminished, 5% Co).

Edling et al. 1988 [114]

Workers at different plants (laminate plants, particle board plants)

0.1–1.1 with exposure peaks of up to 5 (formaldehyde), 0.6–1.1 (wood dust)

75

25

Histological examination

Pathological changes of the nasal mucous membrane in 72 individuals.

^aSchwartz et al. 1989 [119]

Workers at a chemical facility manufacturing acrylates and methacrylates

0.0416–232.96 ethyl acrylate and acrylic acid (mostly around 30 for acrylic acid and 20.8 for ethyl acrylate)

55 (high)

164 (low)

512

UPSIT (identification test)

No association in the first instance between exposure and results of olfactory tests.

^aSchwartz et al. 1989 [119] embedded case-control study

See above

See above

77

77

Dose-effect relationship between olfactory dysfunction and cumulative exposure; the effect appeared to be reversible.

Workers who had never smoked had the highest relative risk of olfactory dysfunction.

Muttray et al. 1997 [120]

Chemical workers in acrylic sheet production

Methyl methacrylate (MMA): 104–416 (1988), 41.6–208 (1989–1994), 9.6 ±7.1 years (mean duration of MMA exposure)

175

88

Rhino Identification Test (6 tested aromas, very similar in design to the UPSIT test)

No significant difference between exposed workers and control group.

Muttray et al. 2007 [121]

Healthy volunteers

208 MMA and room air in an exposure chamber at an interval of one week, in each case for 4 h

20

–

Olfactory threshold for n-butanol (Sniffin’ Sticks)

Olfactory threshold: no changes.

^aCheng et al. 2004 [123]

Injection-moulding workers exposed to acrylonitrile-butadiene-styrene (mainly manufacture of computer shells)

–

52

72

Olfactory threshold test employing 1-butanol,

CCCRC olfactory test (identification)

Slight but significant reduction in olfactory function (threshold) at the end of the shift (whereas the initial situation at the beginning of the shift had been the same).

The identification test revealed no differences before and after the shift.

^aDalton et al. 2003 [124]

Workers in the reinforced-plastics industry

Mean airborne styrene concentrations: 89.2 (day 1), 106.1 (day 2)

Means and ranges of historic exposures to airborne styrene for individual workers (n = 52): 57.37 (15.16–134.23)

Cumulative mean exposure: 675.48 (59.75–1420.24)

Peak year exposure: 112.58 (22.52–331.25)

52

52

Olfactory threshold for phenyl ethyl alcohol and styrene,

retronasal odour identification test with five stimuli,

identification test with 20 odorants

No significant differences between styrene-exposed workers and matched controls in the results of the phenylethyl alcohol threshold test, retronasal test, or odour identification test.

Significantly different odour detection thresholds for styrene among exposed and unexposed groups.

^aDalton et al. 2007 [125]

Workers in a reinforced plastics boat-manufacturing facility

Calculated effective mean concentration of styrene in air: 43.3–108.25 (measured airborne styrene concentration for this group: 303.1–346.4)

15

15

Olfactory threshold for phenyl ethyl alcohol (PEA) and styrene,

identification test with 18 odorants

No significant difference in olfactory threshold for PEA. Significant difference in the threshold test involving styrene among exposed and unexposed groups.

Significant difference in the identification test between workers with high vs. low exposure (possible explanations: more individuals with poor values in both groups than in normal population, cultural and educational differences between the two groups).

^aSchwartz et al. 1990 [130]

Workers in paint manufacturing facilities

Solvents: toluene, xylene and methyl ethyl ketone

Lifetime hydrocarbon dose in ppm years (averages at the two production plants): 180 (±128), 97 (±70)

187

–

UPSIT identification test

Significant dose-dependent deterioration in olfactory function with rising lifetime exposure among workers who had never smoked.

^aSandmark et al. 1989 [131]

Painters

No quantitative exposure measurement (described as “low to moderate”)

54

42

UPSIT identification test

No statistically significant impairment of olfactory function after adjustment for age and smoking habits.

Studies cited in Muttray et al. 1998 [133]: (Dragomitretzky et al. 1970)

(Kmita 1953)

(Latkowski et al. 1981 [134])

Workers at a shoe factory,

petroleum chemistry workers

A petroleum mixture (“Galoscha”), ethyl acetate and butyl acetate (solvent concentration: 220–300),

rubber adhesive containing petroleum (up to 3000)

N. i.

216

205

547

N. i.

N. i.

100 (cotton industry workers)

N. i.

N. i.

Smell and taste tests

31% suffered the loss of olfactory function, and among the remainder, olfactory function was impaired in comparison to a control group.

Olfactory dysfunction as a result of rhinitis arose after a few years.

Hyposmia in 238 (43.5%) and anosmia in 50 (9.2%) subjects.

Dysgeusia in 319 (58.3%).

(Co: dysgeusia in 69%, anosmia in 24% of subjects).

^aAhlstrom et al. 1986 [132]

Tank cleaners

Mineral oil products (heavy and light oils, hydrocarbon content: 240–1615)

20

40

Threshold test, perceived odour intensity test (pyridine, dimethyl disulfide, n-butanol and heated oil vapour)

Elevated olfactory threshold values for heated oil vapour and n-butanol in comparison to controls (for n-butanol within the normal range, oil vapour had not been studied in this respect before).

Higher threshold values for all tested substances exhibited by tank cleaners exposed one day prior to the test in comparison to individuals exposed earlier.

Lower odour intensity values at the lowest stimulus concentrations for all 4 substances in comparison to those of control subjects (“odour intensity recruitment”).