Table 2.

Summary of available studies evaluating respiratory effects.

Author and year of publication	Study description	Route of exposure	Exposure measurement	Outcome(s) evaluated	Outcomes(s) observed	Overall confidence level for outcome	Applicability for dose–response
Human studies (inhalation)
Sucker et al. (2021)	Occupational cross-sectional cross-week study of healthy and nonsmoking male employees at an abrasives plant with either moderate ($n=22$) or high ($n=17$) exposure to naphthalene compared to 22 male employees from the same plants with no or only rare exposure to naphthalene ($n=22$), in Germany or Austria.	Inhalation	Naphthalene levels measured during Thursday shift via personal air monitoring, and naphthalene metabolite levels (1N or 2N) in postshift urine	Preshift (Monday) and postshift (Thursday) measurements of self-reported nose and eye irritation, otorhinolaryngological examination, and evaluation of inflammatory markers in serum, NALF, and sputum.	Increased eye and nasal complaints and increased endoscopic score (based on clinical findings of reddening/swelling nasal mucosa and mucus production) in exposed groups compared to reference group. Decreased serum club cell secretory protein 16 (CC16) after shift Thursday compared to preshift Monday (no statistically significant differences between exposed groups and controls).	Medium. The small sample sizes and the cross-sectional study design may limit the study’s ability to detect an effect. The “healthy worker effect” raises the potential of bias. However, these concerns are expected to have minimal impact on the interpretation of the study.	Suitable. Cross-week study design including air measurement from a full shift, with multiple exposure groups.
Cakmak et al. (2014)	General population cross-sectional health survey of ages 3–79 y old (total of 3,039 nonsmokers; smokers excluded from study) in Canada.	Inhalation	Residential indoor air levels of 84 VOCs, including naphthalene	Lung function as measured by FEV in the first second (FEV1), FVC, and the ${\text{FEV}}_1/\text{FVC}$ ratio	Statistically significant negative association with FEV1, FVC and the ${\text{FEV}}_1/\text{FVC}$ ratio	Medium. All domains were evaluated as at least adequate.	Limited suitability. Cross-sectional study design with limited ability to assess temporality.
Animal studies (inhalation)
Dodd et al. (2012)	Male and female rats (Fischer 344); 90-d exposure	Inhalation (whole body)	0, 0.5, 5.2, 52,$157{\mathrm{mg}/\mathrm{m}}^3$	Nasal histopathology	Increased nasal epithelium lesions in both sexes	High. This study was well-designed to evaluate these outcomes. The only notable concern is that the authors did not describe methods for reducing observational bias in the targeted histopathological evaluation.	Suitable. Multidose study with quantitative data.
Dodd et al. (2010)	Male and female rats (Sprague-Dawley, Fisher 344); 1- or 5-d exposure	Inhalation (whole body)	1-d exposure: 0, 0.5, 1.57, 5.2, 52, $157{\mathrm{mg}/\mathrm{m}}^3$ 5-d exposure: 0, 0.5, 5.2, $52{\mathrm{mg}/\mathrm{m}}^3$	Nasal histopathology	1-d exposure: Increased nasal olfactory epithelium necrosis and respiratory epithelium necrosis in both sexes and strains 5-d exposure: Increased degeneration of nasal olfactory epithelium and nasopharyngeal goblet cell hyperplasia/hypertrophy in both sexes and strains	High. This study was well-designed to evaluate these outcomes. The only notable concern is that the authors did not describe methods for reducing observational bias in the targeted histopathological evaluation.	Suitable. Multidose study with quantitative data (quantitative data provided for males only).
NTP (2000)	Male and female rats (Fisher 344); 2-y (105-wk) exposure	Inhalation (whole body)	0, 52, 157, $314{\mathrm{mg}/\mathrm{m}}^3$	Nasal and pulmonary histopathology	Increased incidence of respiratory epithelial adenomas (statistically significant in males), olfactory epithelial neuroblastomas (positive trend in both sexes, statistically significant in females), and nonneoplastic lesions (statistically significant in both sexes)	High. This study was well designed to evaluate these outcomes. Evidence was presented clearly and transparently.	Suitable. Multidose study with quantitative data.
NTP (1992b)	Male and female mice (B6C3F1); 2-y (103-wk) exposure	Inhalation (whole body)	0, 52, $157{\mathrm{mg}/\mathrm{m}}^3$	Nasal and pulmonary histopathology	Increased incidence of alveolar/bronchiolar adenomas and combined alveolar/bronchiolar adenomas and carcinomas (statistically significant in females; marginal increase in males, but within the historical control rate), and increased incidence of nonneoplastic lesions (statistically significant in both sexes)	High (females). This study was well designed to evaluate these outcomes. Evidence was presented clearly and transparently. Low (males). The high mortality rate in control males has the potential to interfere with the interpretation of results.	Suitable. Multidose study with quantitative data.
Adkins et al. (1986)	Female mice (A/J); 6-month exposure	Inhalation (whole body)	0, 52, $157{\mathrm{mg}/\mathrm{m}}^3$	Pulmonary histopathology	Statistically significant increase in alveolar adenomas	Medium. Some concerns were raised about limited procedural details on the histopathology evaluation, and no description of methods to reduce observational bias.	Suitable. Multidose study with quantitative data.
Animal studies (oral)
Battelle (1980b)	Male and female rats (Fischer 344); 90-d exposure	Oral gavage	0, 25, 50, 100, 200, $400\mathrm{mg}/\mathrm{kg}-\mathrm{d}$	Pulmonary histopathology	No effects observed	High. This study was well designed to evaluate this outcome. Evidence was presented clearly and transparently.	Suitable. Multidose study with quantitative data.
Battelle (1980a)	Male and female mice (B6C3F1); 90-d exposure	Oral gavage	0, 12.5, 25, 50, 100, $200\mathrm{mg}/\mathrm{kg}-\mathrm{d}$	Pulmonary histopathology	No effects observed	High. This study was well designed to evaluate this outcome. Evidence was presented clearly and transparently.	Suitable. Multidose study with quantitative data.
Shopp et al. (1984)	Male and female mice (CD-1); 14- or 90-d exposure	Oral gavage	14-d exposure: 0, 27, 53, $267\mathrm{mg}/\mathrm{kg}-\mathrm{d}$ 90-d exposure: 0, 5.3, 53, $133\mathrm{mg}/\mathrm{kg}-\mathrm{d}$	Lung weight	14-d exposure: Statistically significant increase in absolute and relative lung weight in females; no effects observed in males 90-d exposure: No effects observed	High. This study was well-designed to evaluate this outcome. Evidence was presented clearly and transparently.	Suitable. Multidose study with quantitative data.

Note: FVC, forced vital capacity; FEV1, forced expiratory volume; NALF, nasal lavage fluid; VOC, volatile organic compound.