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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980/04/03-1980/04/29
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: FHSA 16CFR1500.3
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Bu and iso-Pr) esters, zinc salts
EC Number:
288-917-4
EC Name:
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Bu and iso-Pr) esters, zinc salts
Cas Number:
85940-28-9
Molecular formula:
C23.H50.O4.S4.P2.Zn
IUPAC Name:
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Bu and iso-Pr) esters, zinc salts
Details on test material:
Test material was received on 1980/03/27 and described as thick, yellow liquid with specific gravity = 1.17. Stored in refrigerator.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Wistar rats from Ace Animals, at least 8 weeks old upon arrival, were equilibrated for at least one week and housed 5/cage in wire mesh cages. Fresh Purina rat chow and water were administered ad libitum except for 16-20 h prior to dosing when food was removed. Animal room was maintained at 20-21 °C and kept clean in accordance with AAALAC standards.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Test material was administered by gavage. Initially, one group of five male and five female rats were dosed at 5.0 g/kg. Based on those results, three additional groups of five male and five female rats were dosed at 1.04, 2.36, and 3.68 g/kg to determine the LD50.
Doses:
1.04, 2.36, 3.68, and 5.0 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Rats were observed 3-4 h post-dosing and once daily for 14 days. Mortality, toxicity, and pharmacological effects were recorded. Body weights were recorded pretest and at 14 days in survivors.

Statistics:
LD50 calculated according to method of Litchfield, J.T. Jr. and F. Wilcoxon, JPET 96:99, 1949 or Horn, H.J. Biometrics 12:311, 1956.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 080 mg/kg bw
95% CL:
>= 2 570 - <= 3 700
Mortality:
No deaths occurred in the 1.04 g/kg dose group. One male died in the 2.36 g/kg dose group on day two. Four males and four females died in the 3.68 g/kg dose group between days 2 and 3. There were no surviving rats in the 5.0 g/kg dose group by day two.

Clinical signs:
Lethargy, diarrhea, ptosis, and brown staining at the anogenital area were observed in all dose groups and cleared within the first week at the 2 lowest doses. Ataxia was also noted in the higher dose groups and signs generally persisted to death.

Body weight:
Body weight changes were within the expected range at the two lower dose groups.

Gross pathology:
All surviving animals were normal at necropsy. The animals which died during the test were observed to have lung, heart, and gastrointestinal abnormalities.
Other findings:
No other findings recorded.

Any other information on results incl. tables

All of the 5.0 g/kg animals died during the first two days of study. Eight of ten rats treated at 3.68 g/kg died during days 2 through 3. One male at the 2.36 g/kg dose level died on day 2. No deaths occurred at the 1.0 g/kg dose level. Lethargy, diarrhea, ptosis, and brown staining around the anogenital region were noted in all groups. These findings were no longer evident in the two lowest groups within the first week. Body weight changes were within expected ranges for the two lowest dose groups. Lung, heart, and gastrointestinal abnormalities were common necropsy findings for the animals that died.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test article, when administered as received to male and female Wistar rats, had an acute oral LD50 of 3.08 g/kg.
Executive summary:

In an acute oral toxicity study, male and female Wistar rats were exposed to test substance at doses of 1.04, 2.36, 3.68, and 5.0 g/kg. The oral LD50 is 3.08 g/kg. Sublethal effects of lethargy, diarrhea, ptosis, and brown staining at the anogenital area were observed in all dose groups. Necropsy observations included heart, lung and gastrointestinal abnormalities. Based on the results of this study, the test substance would be classified as Category 5 in accordance with the classification system of GHS. This toxicity study is classified as acceptable and satisfies the guideline requirement for acute oral toxicity in rats.

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