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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976/12/06-1980/08/28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: While this 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:
no guideline available
Guideline:
other: Protocol 159 and 159-01 referenced
Deviations:
yes
Remarks:
Deviation only in dose calculation due to incorrect specific gravity in initial study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Half the animals were abraded and less than 5 animals were used/sex/dose
Principles of method if other than guideline:
Four 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:
yes
Remarks:
Quality assurance reviewed 1980/08/18, 1980/09/03, 1980/10/13 and signed of 1980/10/16
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)
EC Number:
218-679-9
EC Name:
Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)
Cas Number:
2215-35-2
Molecular formula:
Too complex
IUPAC Name:
zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)
Details on test material:
Test material is described as amber liquid with specific gravity of 1.1


Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals were approximately 8 weeks old when received and equilibrated for at least one week in the laboratory. Apparently healthy rabbits were selected for the test. The animals were identified by cage tags noting the test article, starting date, animal number and sex. In addition, each animla was identified by a numbered metal eartag or an indelible earmark. The animals were housed in suspended wire mesh cages and 2/cage in initial study and 1/cage in repeated study. Fresh Purina rabbit chow and water were freely available and the animal was kept temperature controlled and cleaned in accordance with AAALAC standards. Animals were received from Ace Animals for the initial study and a combination of Ace Animals, Perfection Breeders, and Nicholas Helf for the repeated study.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Immediately prior to dosing, a 200 square cm area was clipped from the abdomen of the animals. Abasions were made in one half of the animals that extended the length of the exposure site and scratched the stratum corneum without reaching the derma or producing bleeding. The test article was applied once dermally to the prepared site under gauze patches and secured with adhesive tape and the trunks were wrapped with impervious material. The test article was kept 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 excess material.
Duration of exposure:
24 h
Doses:
9.9, 17.6, 24.2, 30.2 g/kg
No. of animals per sex per dose:
2-6; D1: 5 males, 3 females; D2: 6 males, 2 females; D3: 2 males, 6 females; D4: 4 males, 4 females
Control animals:
no
Details on study design:
Dermal reactions were scored by Draize scoring system at 24 h in initial study and at 1, 7 and 14 days in the repeated study. 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. Necropsy was performed in animals that died during the study for the initial test and all animals in the repeated test due to poor condition of the rabbits on day 14.


Statistics:
LD 50 was calculated according to the method of Litchfield J.T. Jr. and F. Wilcoxon (1949) or Horn H.J. Biometrics

Results and discussion

Preliminary study:
Results from initial 20 g/kg study not available.

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 25 000 mg/kg bw
Mortality:
2/5 male and 1/3 female at 9.9 g/kg, 3/6 male and 1/2 female at 17.6 g/kg, 0/2 male and 2/6 female at 24.2 g/kg, and 2/4 male and 0/4 female at 30.2 g/kg.
Clinical signs:
Toxic signs included few feces, yellow nasal discharge, alopecia, emaciation, lethargy and ptosis. Skin reactions were generally moderate on Day 1, but worsened during the latter part of th study with the formation of severe eschar accompanied by moderate to severe edema.


Body weight:
All surviving animals lost weight.

Gross pathology:
Necropsy of the survivors and spontaneous deaths showed skin abnormalities and wasting of the body. The animals found dead also exhibited heart dilation and lung abnormalities. One of these had a hemorrhagic kidney and fluid in the body cavity.
Other findings:
The severe skin reactions decreased appetite and mobility which is believed to have contributed to deaths in 10/11 animals from which death occurred on or after Day 6.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, the test material was practically non-toxic when applied dermally to male or female New Zealand White Rabbits.
Executive summary:

In an acute dermal toxicity study, New Zealand White rabbits were exposed to the test substance at concentrations of 9.9, 17.6, 24.2 and 30.2 g/kg. The LD50 on Day 14 post-exposure was greater than 25 g/kg. Toxic signs observed in all dose groups included few feces, yellow nasal discharge, alopecia, emaciation, lethargy and ptosis. Based on the results of this study, this 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.