TOXICOLOGICAL PROFILE FOR
1,4-DITHIANE
Criteria and Standards Division
Office of Drinking Water
U.S. Environmental Protection Agency
Washington, DC 20460
June, 1989
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TOXICOLOGICAL PROFILE
FOR
1,4-DITHIANE
June 1989
Criteria and Standards Division
Office of Drinking Water
U.S. Environmental Protection Agency
Washington, DC 20460
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1,4-DITHIANE
A. GENERAL
1. CAS Number; 505-29-3
2. RTECS Number;
3. General Name/Svnonvms; Diethylene dlsulfide
p-Dlthiane
4. Molecular Formula; C4H8S2
5. Molecular Weight: 120.23
6. Structure;
O
B. PHYSICAL AND CHEMICAL PROPERTIES
1. State: Moderately clear, prism shaped
crystals.
2. Vaoor Pressure: No information was found.
Weast (1988)
3. Melting Point: 111-112°C
4. Boiling Point: 199-200°C
Weast (1988)
Weast (1988)
5. Specific Gravity; No information was found.
6. Solubility; Soluble in ethanol and alcohol
Weast (1988)
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7. Log Kn...: No information was found.
8. UV Absorption; No information was found.
C. PHYSICAL/CHEMICAL EQUILIBRIUM FACTORS
1. Bioconcentration Factors (BCD: No information was found.
2. Kwa: No information was found.
3. ^e: No information was found.
D. ENVIRONMENTAL FATE
1. Photolysis: No information was found.
2. Leaching; No information was found.
3. Route of Water Contamination: No information was found.
4. Hydrolysis; No information was found.
5. Plant Uptake; No information was found.
6. Microbial Degradation: No information was found.
7. Persistence in Soil/Water: No information was found.
8. Byproducts: No information was found.
9. Vaporization: No information was found.
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E. ACUTE TOXICITY IN MAMMALS
Animal/strain/sex
Rat/F344/M
Route LDjo (mg/kg) Effects Reference
Oral 3680 Antemortem observations Included Mayhew and Muni (1986)
I
LJ
I
Oral
Combined
crusty eyes/nose/muzzle, hyper-
activity, muscle tremors, red
stained fur around eyes, emaciation,
lethargy, few or no stools, ataxla,
squinting, prostration, lacrimation,
irregular breathing, damp and
yellow/brown stained fur in peri anal
region, and test article odor present
in animal room (up to day 5 post-
treatment).
2768 Necropsy of animals found dead revealed
red or dark red discoloration of lungs;
pale or red discoloration on parts or
all of small intestine; gastrointestinal
contents that were dark, black, thick, red,
fluid, and/or white; black discoloration
of stomach; black or red discolorations
and/or smooth mucosa of glandular
stomachs; pale or tan discolorations
of liver; yellow fluid around mouth;
yellow or green yellow discoloration of
oral region; salivation around mouth; or
black discolored fur around rectum.
3473 Necropsy of one terminal sacrifice
female of the 3981-mg/kg dose group
revealed a solitary red cyst of
the left ovary.
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Schieferstein et al. (1988) administered, by gavage, to groups of six
male and six female CD rats single daily doses of 0, 25, 50, 100, 210, or 420
mg/kg 1,4-dithiane in sesame oil for 14 days. No mortality, no overt signs of
toxicity, and no treatment-related effects on water or food consumption were
observed. At the high dose (420 mg/kg/day), decrements in body weight gain of
5.3 and 8% were seen in males and females, respectively, but these were not
statistically significant (p >0.05).
F. SKIN AND EYE IRRITATION AND SENSITIZATION IN MAMMALS
No information was found.
G. SUBCHRONIC TOXICITY IN MAMMALS
Groups of 30 male and 30 female CD rats were administered 1,4-dithiane in
sesame oil, by gavage, at 0, 105, 210, or 420 mg/kg/day for 90 days. Rats
were observed twice daily, and body weights, water and food consumption, and
clinical observations were made weekly. Animals were examined
ophthalmologically before treatment initiation and during study week 12. At
termination, tissues from all high-dose and control animals were examined
histopathologically. No significant treatment-related ophthalmologic changes
or effects on survival, body weight, or food and water consumption were
observed. Regression analyses revealed a significant (p <0.05) treatment-
related increase in female liver weights, a decrease in female brain weights,
and increases in male kidney and thymus weights. Significant (p <0.05)
changes in organ weights of treated rats compared with control organ weights
were seen in the low-dose (105 mg/kg/day) group in the spleens of both sexes,
female brain, and male kidneys. Hispathological examination revealed
treatment-related changes in the nose, liver, and kidneys. Nasal lesions
included the deposition of anisotrophic crystals of an undetermined chemical
composition in the olfactory nasal mucosa of both sexes; the severity was
greatest in the high-dose (100%) and the mid-dose (100%) groups compared with
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the low-dose (6-7%) and control (0%) groups. Liver lesions were limited to
high-dose females and included minimal hypertrophy in the centrilobular region
and minimal cytoplasmic vacuolation in the periportal region. Renal lesions
and eosinophilic cytoplasmic renal granules were observed in 92% of the high-
dose males; no renal lesions were observed in males at the mid- or low-dose
levels. Based on the histopathologic changes noted, the No Observed Adverse
Effect Level (NOAEL) in this study was 105 mg/kg/day (Schieferstein et al.,
1988).
H. REPRODUCTION AND TERATOGENICITY IN MAMMALS
No information was found.
I. MUTAGEN1CITY/GENOTOXICITY
Data are presented in tabular form on page 6.
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I. MUTAGENICITY/GENOTOXICITY
Test
Strain
Activation
Dose/concent rat i on
Toxic effects
Reference
Ames nutagenicity
assay
Salmonella
tvphimurium
TA 90. TA 100
+S9
0.0016. 0.008.
0.04, 0.2. 1.
or 5 ing/plate
No mutagenicity.
Sano and Korte (1985)
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J. CHRONIC/CARCINOGENICITY STUDIES IN MAMMALS
No Information was found.
K. PHARMACOKINETICS IN MAMMALS
No information was found.
L. HUMAN HEALTH EFFECTS
No information was found.
M. EXISTING STANDARDS/CRITERIA
No information was found.
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N. REFERENCES
Mayhew DA, Muni IA. 1986. Dermal, Eye, and Oral Toxicological Evaluations.
Phase II. Acute Oral LD50 Determinations of Benzothiazole, Diathiane, and
Oxathiane. Fort Detrick, MD: U.S. Army Medical Research and Development
Command. Available from OTIC. AD-A172647.
Sano S, Korte D. 1985. Mutagenic Potential of p-Dithiane. Fort Detrick, MD:
U.S. Army Medical Research and Development Command. Institute Report No. 207.
Available from DTIC. AD-A165756.
Schieferstein CJ, Sheldon WG, Cantrell SA, Reddy G. 1988. Subchronic
toxicity study of 1,4-dithiane in the rat. Fund. Appl. Toxicol. 11:703-714.
Weast RC. 1988. CRC Handbook of Chemistry and Physics. 69th Ed. Boca
Raton, FL: CRC Press, Inc.
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