Reaction Products of Diphosphorus Pentaoxide with n-Alcohols, C8-10 (even), salted with Amines, C12-14, Tert-alkyl

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-12-02 - 1995-09-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Scientifically valid GLP study on the registered substance itself according to US EPA guideline 81-2

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction Products of Diphosphorus Pentaoxide with n-Alcohols, C8-10 (even), salted with Amines, C12-14, Tert-alkyl

EC Number:

943-016-1

Molecular formula:

Too complex

IUPAC Name:

Reaction Products of Diphosphorus Pentaoxide with n-Alcohols, C8-10 (even), salted with Amines, C12-14, Tert-alkyl

Test material form:

other: liquid

Details on test material:

- Substance type: pure substance
- 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:

TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN, USA
- Age at study initiation: adult
- Weight at study initiation: 2442 - 2995 g
- Fasting period before study: none
- Housing: The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5322 was provided ad libitum to the animals throughout the study.
- Water (e.g. ad libitum): Municipal tap water treated by reverse osmosis was available to the animals ad libitum throughout the study.
- Acclimation period: Min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 61-71° F (16.1-21.7°C)
- Humidity (%): 16-60%
- Air changes (per hr): 10 - 12
- Photoperiod (hrs dark / hrs light): 12h / 12h

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10% of the body surface area (BSA)
- % coverage: 100%
- Type of wrap if used: The test item was held in contact with the skin with an appropriately sized 4 ply porous gauze dressing backed with plastic wrap (occlusive binding). Removal and ingestion of the test article was prevented by placing an elastic wrap over the trunk and test area. The elastic wrap was further secured with adhesive tape around the trunk at the cranial and caudal ends.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The residual test article was removed using gauze moistened with USP grade mineral oil followed by dry gauze.
- Time after start of exposure: approximately 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): n/a, test item was applied undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 / sex / dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Limit test animals were observed for clinical abnormalities two times on study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon. Limit test animals were examined for erythema and edema following patch removal on study day 1 and daily thereafter (days 2-14). Individual body weights were obtained for the limit test animals prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined.

Statistics:

none

Results and discussion

Preliminary study:

not applicable

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred during the limit test.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred during the limit test.

Mortality:

No mortality occurred during the limit test.

Clinical signs:

The most notable clinical abnormalities observed during the study included transient incidences of fecal stain and dark material around the facial area. Dermal irritation was noted at the site of test article application.

Body weight:

Body weight gain was noted for all animals during the test period.

Gross pathology:

8/10 showed no significant changes. One male had a thickened subcutis (caudal portion of the application site) of the treated skin and bilateral enlarged cervical lymph nodes, and one female had a thickened subcutis (encompassing entire test application site).

Any other information on results incl. tables

Table 1: Individual body weights in grams

Day	0	7	14	Day	0	7	14
Animal	males			Animal	females
51877	2471	2581	2904	51912	2431	2488	2732
51878	2446	2681	2935	51931	2571	2702	2902
51880	2955	2520	2759	51932	2458	2598	2829
51881	2456	2683	2935	51933	2495	2515	2770
51883	2475	2502	2746	51934	2397	2442	2657
Mean	2441	2593	2856	Mean	2470	2549	2778
SD	49.2	86.0	95.3	SD	66.7	102.6	93.3
N	5	5	5	N	5	5	5

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study is well-documented and was performed according to EPA OPP 81-2 (Acute Dermal Toxicity), under GLP conditions. Hence, the information provided in the report can be considered reliable. In consequence, the results are suitable for the assessment of the acute dermal toxicity of the test item. Under the conditions of this test, the acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rabbit.

Executive summary:

In an acute dermal toxicity study (EPA OPP 81-2), groups of young adult New Zealand White rabbits (5/sex) were dermally exposed to the undiluted test item for 24 hours to 10% of body surface area at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

 

Dermal LD50 was determined to be:

Males >2000 mg/kg bw

Females >2000 mg/kg bw

Combined >2000 mg/kg bw

 

No mortality occurred during the limit test. The most notable clinical abnormalities observed during the study included transient incidences of fecal stain and dark material around the facial area. Dermal irritation was noted at the site of test article application. Body weight gain was noted for all animals during the test period. Thickened subcutis was noted in 2/10 animals.

 

The test item is of low toxicity and does not trigger classification, the study is classified as acceptable.