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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980/4/08-1980/4/22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: While this non-GLP study is similar to current guidelines, it does deviate significantly enough to warrant 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: 16CFR1500.3
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
2 rather than 5 animals/sex were evaluated for toxicity and the skin of one animal/sex was abraded.
Principles of method if other than guideline:
One group of 2 male and 2 female rabbits were dosed at 20 g/kg and exposed dermally for 24 h under gauze dressing as described. If deaths occurred at the initial level, 3 additional groups of 4 rabbits are dosed at log intervals in an attempt to determine the LD 50.

GLP compliance:
no
Remarks:
QA reviewed on 4/24/80, 5/14/80 and signed off on 5/28/80
Test type:
standard acute method
Limit test:
yes

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 is described as amber liquid with specific gravity of 1.17


Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals supplied by Nicholas Helf were approximately 8 weeks old and weighed between 2.5-2.8 kg when received. The animals were equilibrated to the laboratory for 1 week. Apparently healthy rabbits were selected for the test and identified by cage tags and numbered metal eartag. Animals were housed 1/cage in suspended wire mesh cages. Fresh Purina rabbit chow and water were freely available. The animal room was temperature controlled and kept clean in accordance with AAALAC standards.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Immediately prior to dosing, the fur was clipped from the abdomen of the animals. The clipped area was 200 square cm. Abrasions were made in one half of the rabbits and extended the length of the exposure site. The abrasions scratched the stratum corneum but did not reach the derma or produce bleeding. Test material was applied once dermally under gauze patches, secured with adhesive tape, and wrapped around the trunks with an impervious material.

Duration of exposure:
Test material was held in contact with the skin for 24 h, at which time the wrappings were removed. The exposure site was wiped, but not washed, to remove any excess material.
Doses:
20 g/kg

No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
Dermal reactions were scored at 1,7, and 14 days by the Draize scoring system. The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in the survivors at 14 days. Gross necropsies were performed on all animals on Day 14.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Mortality:
All animals survived the test.


Clinical signs:
Lethargy, ataxia, alopecia, and emaciation were noted in most animals throughout the test. Well defined to severe redness and edema were observed throughout the study period and were not reversible by Day 14. On Day 7, the treated areas were pale, cracked and bleeding, and inflamed. All animals exhibited peeling of the skin by Day 14.
Body weight:

All treated animals lost weight during the study.

Gross pathology:
No data.
Other findings:
No data.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The test article, when administered dermally as received to 2 male and 2 female New Zealand white rabbits had an acute dermal LD50 of greater than 20.0 g/kg. While there were many local effects at the treatment site, there was no evidence of systemic toxicity.
Executive summary:

In an acute dermal toxicity study, male and female New Zealand White rabbits were exposed to 20 g/kg of test substance. The LD50 on Day 14 post-exposure was greater than 20 g/kg. Toxic signs observed in most animals included lethargy, ataxia, alopecia, and emaciation. Based on the results of this study, the test substance would not be classified in accordance with the classification system of GHS. This toxicity study is classified as acceptable and satisfies the guideline requirement for acute dermal toxicity in rabbits.