The Toxicology of 1,4-Dioxane - Environmental Investigation and Remediation - page 233

TABLE 5.2
Acute and Short-Term Toxicity Studies of 1,4-Dioxane (Less than 1-Month Exposure)

Animal Exposure Route Test Conditions Results Dose a References

Oral Studies
Rat (inbred strain
and gender
unspecii ed)

Oral via drinking
water

Drinking-water exposure for
1-10 days

Ultrastructural changes in the kidney, degenerative
nephrosis, hyaline droplet accumulation, crystal
formation in mitochondria

11,000 mg/kg-day (5%) David (1964)

Rat (strain and
gender unspecii ed)

Oral via drinking
water

Drinking-water exposure for
5-12 days

Extensive degeneration of the kidney, liver
damage, mortality in 8/10 animals by 12 days

11,000 mg/kg-day (5%) Kesten et al.

(1939)

F344/DuCrj rat Oral via drinking

water

Drinking-water exposure for
14 days

Mortality, decreased body weights,
histopathological lesions in the nasal cavity, liver,
kidney, and brain

2500 mg/kg-day (nuclear
enlargement of olfactory epithelial
cells),

JBRC (1998a)

7500 mg/kg-day for all
other effects

>

Male Sprague
Dawley rat

Gavage Single-dose gavage Decreased dopamine and serotonin content of the

hypothalamus

1050 mg/kg-day Kanada et al.

(1994)

Female Sprague
Dawley rat

Gavage 0, 168, 840, 2550, or

4200 mg/kg by gavage;
21 and 4 h prior to sacrii ce

Increased ODC activity, hepatic CYP450 content,
and DNA single-strand breaks

840 mg/kg (ODC activity only) Kitchin and

Brown (1990)

Female Carworth
Farms-Nelson rat

Gavage Single-dose gavage Lethality LD 50 = 6400 mg/kg (14,200 ppm) Pozzani et al.

(1959)

Male Wistar rat,
guinea pig

Gavage Single-dose gavage Lethality Smyth et al.

(1941)

LD 50 (mg/kg): rat = 7120, guinea
pig = 3150

Rat, mouse, and
guinea pig

Gavage Single-dose gavage Clinical signs of CNS depression, stomach

hemorrhage, kidney enlargement, and liver and
kidney degeneration

Laug et al. (1939)

LD 50 (mg/kg): mouse = 5900,
rat = 5400, and guinea pig = 4030

Rabbit Gavage Single-gavage dose of 0, 207,

1034, or 2068 mg/kg-day

Clinical signs of CNS depression, mortality at
2068 mg/kg, renal toxicity (polyuria followed by
anuria), histopathological changes in liver and
kidneys

1034 mg/kg-day de Navasquez

(1935)

Rat, rabbit Gavage Single dose; mortality after

two weeks

Mortality and narcosis 3160 mg/kg Nelson (1951)

continued