Registration Dossier

Diss Factsheets

Administrative data

acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
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 Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
other: 16CFR1500.3
equivalent or similar to guideline
OECD Guideline 402 (Acute Dermal Toxicity)
Half the animals had abrasions to the skin 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:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts
EC Number:
EC Name:
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts
Cas Number:
Molecular formula:
Too complex
Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts
Details on test material:
Test material is described as amber liquid with specific gravity of 1.2

Test animals

New Zealand White
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 animal 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. 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 a combination of Ace Animals, Perfection Breeders, and Nicholas Helf and with weights between 2.0 and 2.9 kg.

Administration / exposure

Type of coverage:
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
10240, 12800, 16000, 20000 mg/kg
No. of animals per sex per dose:
4; D1: 2 males, 2 females; D2: 4 females; D3: 4 females; D4: 2 males, 2 females
Control animals:
Details on study design:
Dermal reactions were scored by Draize scoring system at 24 h. 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.

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

Effect levels
Dose descriptor:
Effect level:
13 800 mg/kg bw
95% CL:
10 900 - 17 400
No deaths occured at the 10,240 mg/kg dose level, 2/4 females died on Days 11 and 13 at the 12,800 mg/kg dose level, 3/4 females died at the 16,000 mg/kg dose level, and 2/2 males and 1/2 females dies at the 20,000 mg/kg dose level.
Clinical signs:
other: Toxic signs included few feces, yellow nasal discharge, alopecia, emaciation, coma, ptosis, diarrhea, ataxia, anorexia and adipsia. At 24 h, very slight to moderate erythema was observed at all doses with severity increasing with dose level. Very slight
Gross pathology:
Necropsy observations included lung, heart and gastrointestinal abnormalities. Severe skin reactions were also observed at 15,000 and 20,000 mg/kg and loss of body fat and muscle at 12,800 and 16,000 mg/kg.
Other findings:
White nodules in the liver, pale kidney, and small spleen were observed at the highest dose level and were considered non-specific by the study director.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Migrated information
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 10240, 12800, 16000, 20000 mg/kg. The LD50 on Day 14 post-exposure was 13,800 mg/kg. Toxic signs observed in all dose groups included mucus in feces, yellow nasal discharge, alopecia, 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.