. 2021 Jul 12;129(7):076002. doi: 10.1289/EHP7381

Table 3.

Summary of available studies evaluating hematologic effects.

Author and publication year	Study description	Route of exposure	Exposure measurement	Outcome(s) evaluated	Outcomes(s) observed	Overall confidence level for outcome	Applicability for dose–response
Human studies (nonspecific route of exposure)
Sudakin et al. (2013)	Cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) 2003–2004 (a sample of noninstitutionalized U.S. civilians, selected by a complex, multistage probability design) data on 2,450 adults ( $18 +$ y old) without treated anemia and with complete data on naphthalene, hemoglobin, and hematocrit	Nonspecific route of exposure	Urinary biomarkers of naphthalene exposure (1N or 2N)	Hemoglobin and hematocrit levels	Statistically significant positive association of hemoglobin and hematocrit levels with 1N; no association with 2N	Medium. All domains were evaluated as at least adequate.	Limited suitability. Cross-sectional study design with limited ability to assess temporality. Also, insufficient availability of data or models to relate urinary metabolites to exposure levels.
Kamal et al. (2014)	Occupational case–control study of 46 male brick kiln workers compared with 34 nonoccupationally exposed workers in Pakistan	Nonspecific route of exposure	Naphthalene metabolite levels (1N or 2N) in postshift urine	Hemoglobin, mean corpuscle volume, and platelet, erythrocyte, and total leukocyte counts	Statistically significantly lower hemoglobin, erythrocytes, and mean corpuscular volume and increased leukocytes in exposed vs. unexposed workers	Low. Domains for exposure measures, confounding, analysis, and sensitivity were evaluated as deficient.	Limited suitability. Insufficient availability of data or models to relate urinary metabolites to exposure levels.
Santucci and Shah (2000)	General population cross-sectional health survey of 24 children (age 2 wk to 18 y) hospitalized with glucose 6-phosphate dehydrogenase deficiency and acute hemolysis in the United States (New York).	Nonspecific route of exposure	Retrospective chart review; no exposure level data	Hemolysis	Hemolytic anemia associated with self-reported exposure to naphthalene-containing moth repellents	Low. Domains for exposure measures, confounding, and analysis were evaluated as deficient.	Not suitable. No quantitative exposure level data.
Animal studies (inhalation)
NTP (1992b)	Male and female mice (B6C3F1); 2-year (103-wk exposure), hematology evaluated at 14 d	Inhalation (whole body)	0, 52, $157 {mg / m}^{3}$	Hematocrit, hemoglobin, mean cell (corpuscular) volume, and erythrocyte, reticulocyte, and total leukocyte counts	Statistically significant decrease in hematocrit and mean corpuscular volume and increase in leukocyte count in females	Medium. This study appears to be well-designed to evaluate these outcomes, but lacked details on the methods for the hematological evaluation. The high mortality rate in the control males is not a major concern for the hematological evaluation because it was performed on day 14, which was before there was a large difference in survival between experimental groups.	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, $400 mg / kg - d$	Hemoglobin, hematocrit, mean corpuscular volume, erythrocyte count, and total and differential leukocyte count	Decreased hemoglobin and hematocrit and increased mature neutrophils in both sexes; decreased lymphocytes in males	Medium. This study appears to be well-designed to evaluate these outcomes, but lacked details on the methods for the hematological evaluation.	Suitable. Multidose study with quantitative data.
Battelle (1980a)	Male and female mice (B6C3F1); 90-d exposure	Oral gavage	0, 12.5, 25, 50, 100, $200 mg / kg - d$	Hemoglobin, hematocrit, mean corpuscular volume, erythrocyte count, and total and differential leukocyte count	No effects observed	Medium. This study appears to be well-designed to evaluate these outcomes, but lacked details on the methods for the hematological evaluation.	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, $267 mg / kg-d$ 90-d exposure: 0, 5.3, 53, $133 mg / kg - d$	Hemoglobin, erythrocyte, platelet, and differential leukocyte counts, plasma extrinsic activity (prothrombin time) and intrinsic activity (activated partial thromboplastin time)	14-d exposure: Statistically significant increase in eosinophils in males; decreased prothrombin time in females 90-d exposure: Statistically significant increase in hemoglobin, activated partial thromboplastin time, and eosinophils in females	Medium. This study was well-designed to evaluate these outcomes, but confidence was decreased because only qualitative results are provided.	Not suitable. Quantitative data not reported.
Katsnelson et al. (2014)	Female rats (strain unspecified); 7-wk exposure	Oral gavage	0, $87.5 mg / kg - d$	Hemoglobin, and erythrocyte, reticulocyte, lymphocyte, neutrophil, and eosinophil counts	Statistically significant decrease in segmented neutrophils	Low. Concerns were raised because no information was provided on the source and purity of the test chemical or the use of a vehicle control, animal strains were not reported, and no experimental details are provided on the hematological evaluation.	Limited suitability. Single dose study.
Animal studies (dermal)
Bushy Run (1986)	Male and female rats (Sprague-Dawley CD); 90-d exposure	Dermal	0, 100, 300, $1,000 mg / kg - d$	Hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte count, total and differential leukocyte count, platelet count	No effects observed	High. This study was well designed to evaluate these outcomes. Evidence was presented clearly and transparently.	Suitable. Multidose study with quantitative data.