The Toxicology of 1,4-Dioxane - Environmental Investigation and Remediation - page 238

TABLE 5.3
Subchronic and Chronic Oral Toxicity Studies for 1,4-Dioxane

Lowest Dose with
Signifi cant Increase
in Tumor Incidence
(mg/kg · day) a

NOAEL
(mg/
kg · day)

LOAEL (mg/
kg · day)

Noncancer Effects at the
LOAEL Dose

Target Organ and Tumor
Type (if Applicable) Species Dose/Duration References

Subchronic Studies
Rat and mouse (six
per species);
unknown strain

Rats 0 or 1900 mg/kg-day; mice 0
or 3300 mg/kg-day for 67 days

NA 1900 (rats)

3300
(mice)

Renal cortical degeneration
and necrosis, hemorrhage;
hepatocellular degeneration

NA NA Fairley et al.

(1934)

Male Sprague
Dawley rat (four to
six per group)

0, 10, or 1000 mg/kg-day for
11 weeks

10 1000 Minimal centrilobular

hepatocyte swelling;
increased DNA synthesis

NA NA Stott et al.

(1981)

F344/DuCrj rat (10
per sex per group)

Males 0, 60, 150, 330, 760, and
1900 mg/kg-day; females 0, 100,
200, 430, 870, and 2020 mg/
kg-day for 13 weeks

60 150 Nuclear enlargement of nasal

respiratory epithelium;
hepatocyte swelling

NA NA JBRC

(1998b)

Crj:BDF 1 mouse (10
per sex per group)

Males 0, 100, 260, 580, 920, or
1830 mg/kg-day; females 0, 170,
410, 920, 1710, or 2700 mg/
kg-day for 13 weeks

170 410 Nuclear enlargement of

bronchial epithelium

NA NA JBRC

(1998b)

Chronic Studies
Male Wistar rat (26
treated, nine
controls)

0 or 640 mg/kg-day for 63 weeks NA 640 Hepatocytes with enlarged

hyperchromic nuclei;
glomerulonephritis

Liver (hepatocellular
carcinoma)

640 Argus et al.

(1965)

Male Sprague
Dawley rats (30 per
group)

0, 430, 574, 803, and 1032 mg/
kg-day for 13 months

NA 430 Hepatocytomegaly;

glomerulonephritis

Nasal cavity (squamous cell
carcinoma), liver
(hepatocellular carcinoma)

NA b Argus et al.

(1973),
Hoch-Ligeti
et al. (1970)