Zinc bis[O-(6-methylheptyl)] bis[O-(sec-butyl)] bis(dithiophosphate)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 to 22 May 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to OECD guidelines (with certain deviations)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

groups of two animals per sex tested, instead of the indicated five of a single sex. Patch was occluded, rather than semi-occluded

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zinc bis[O-(6-methylheptyl)] bis[O-(sec-butyl)] bis(dithiophosphate)

EC Number:

298-577-9

EC Name:

Zinc bis[O-(6-methylheptyl)] bis[O-(sec-butyl)] bis(dithiophosphate)

Cas Number:

93819-94-4

Molecular formula:

C16H36O4P2S4Zn-C32H68O4P2S4Zn neutral salt; C48H108O13P6S12Zn4- C96H204O13P6S12Zn4 basic salt

IUPAC Name:

2,6-bis(butan-2-yloxy)-2,6-bis[(6-methylheptyl)oxy]-1λ³-thia-3λ³-thia-5λ³-thia-7λ³-thia-2λ⁵,6λ⁵-diphospha-4-zincaspiro[3.3]hepta-2,6-diene-4,4-bis(ylium)-1,5-diide

Details on test material:

- Name of test material (as cited in study report): MRD-80-22
- Substance type: technical product
- Physical state: dark amber liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Dutchland Laboratory Animals Inc., Denver, Pennsylvania
- Age at study initiation: "young adults"
- Weight at study initiation: 2.2-2.6 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-20
- Humidity (%): no data ("monitored daily")
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 8 May 1980 To: 22 May 1980

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and ventral surface from scapular to pelvic area
- % coverage: 20% of body surface
- Type of wrap if used: gauze covered with an impervious plastic sleeve secured with masking tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped free of excess test substance; no washing
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.044, 0.175, 0.696 or 2.772 ml/kg bw
- Constant concentration used: yes, neat

Duration of exposure:

24 hr

Doses:

50, 200, 794 or 3160 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observations for mortalities - twice daily;
clinical observations - 1, 2 and 4 h post-dosing, then daily;
body weights - day -1 (time of clipping), days 0, 7 and 14;
irritation - 30 min after removal of the patch
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and skin irritation (erythema and edema)

Statistics:

no data

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no CL given in the report

Mortality:

All animals survived

Clinical signs:

other: At 200, 794 and 3160 mg/kg bw, several animals had soft faeces and faecal staining on some days throughout the study; however the number of animals involved and frequency of occurrence were not dose-related.

Gross pathology:

Changes observed occurred in the majority of animals at all dose levels, but their severity did not appear to be dose-related. These changes included diminished and roughened spleens, red or tan coloured lungs, vascularized stomach and/or intestines and red foci in the adrenals.

Other findings:

At the application site (30 minutes after patch removal), very slight to severe erythema (grade 1-3) was evident at 50 and 200 mg/kg bw, and moderate to severe erythema (grade 3) at 794 and 3160 mg/kg bw. Edema ranged from absent to very slight (grade 0-1) at the lowest dose, absent to well-defined (grade 0-2) at 200 mg/kg bw, very slight to well-defined (grade 1-2) at 794 mg/kg bw and well-defined (grade 2) at the highest dose.

Exfoliation of the skin was evident during the second week at the application site at the highest dose and skin necrosis was present in two of these animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No mortalities occurred up to 14 days after application of undiluted MRD-80-22 to the shaved skin of rabbits (2/sex/dose) at up to 3160 mg/kg bw under an occluded patch for 24 h.

Executive summary:

Test material MRD-80-22 was assessed for acute dermal toxicity in New Zealand White rabbits in a protocol similar to OECD guideline 402. Doses of the undiluted liquid were applied to the shaved skin of groups of two animals/sex at 50, 200, 794 or 3160 mg/kg bw under an occluded patch. After 24 hours, the patch was removed and the test site wiped free of excess test material. Observations were carried out during a 14-day period, after which the animals were subject to necropsy.

No deaths occurred during the study. At 200, 794 and 3160 mg/kg bw, several animals had soft faeces and faecal staining on some days throughout the study; however the number of animals involved and frequency of occurrence were not dose-related. All animals had gained in body weight at study termination, except two females at 794 mg/kg bw which showed no weight change. Changes observed at necropsy occurred in the majority of animals at all dose levels, but their severity did not appear to be dose-related. These changes included diminished and roughened spleens, red or tan coloured lungs, vascularized stomach and/or intestines and red foci in the adrenals. Erythema and edema was observed at all dose levels and tended to be dose-related in severity. Exfoliation of the skin was evident during the second week at the application site at the highest dose and skin necrosis was present in two of these animals.

In conclusion, under the test conditions, since the LD50 was considered >3160 mg/kg bw, MRD-80-22 would not be classified for acute dermal toxicity according to the EU CLP Regulations or the Dangerous Substances Directive.