Dimethyl octadecylphosphonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1971-12-02 to 1972-01-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP/non-guideline study (this study was conducted in the United States prior to issue of the OPPTS harmonised Test Guidelines).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

Test guideline

Test guideline 1

Qualifier:

no guideline available

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not applicable

Principles of method if other than guideline:

Undiluted dimethyl octadecyl phosphonate (DMOP) was applied to the closely clipped, intact skin of New Zealand white male and female rabbits.at 5 dose levels ranging from 1260 mg/kg to 7940 mg/kg (one animal per dose rate (male animals were dosed at 1260, 3160 and 7940 mg/kg; female animals were dosed at 2000 and 5010mg/kg). The treated areas were covered with occlusive dressings and the animals were observed for clinical signs for a period of 14 days (or until death). Necropsy of all animals was performed.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl octadecylphosphonate

EC Number:

246-904-0

EC Name:

Dimethyl octadecylphosphonate

Cas Number:

25371-54-4

Molecular formula:

C20H43O3P

IUPAC Name:

dimethyl octadecylphosphonate

Constituent 2

Reference substance name:

M-5925

IUPAC Name:

M-5925

Test material form:

other: M-5925 is a waxy solid (not specified in the report)

Details on test material:

Identification: M-5925
Test substance adminstered undiluted, warmed to 115°F (46°C), to liquefy
Purity: Not reported

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: 2.4 - 2.7 kg
- Fasting period before study: Not reported
- Housing: Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Undiluted DMOP was applied at 1260, 2000, 3160, 5010 and 7940 mg/kg (one animal per dose rate (male animals were dosed at 1260, 3160 and 7940 mg/kg; female animals were dosed at 2000 and 5010mg/kg) to the closely clipped, intact skin of New Zealand white male and female rabbits. The treated areas were covered with plastic strips and the animals held in wooden stocks for periods up to twenty four hours, after which time they were assigned to individual cages.

Duration of exposure:

24 hours

Doses:

1260, 2000, 3160, 5010 and 7940 mg/kg

No. of animals per sex per dose:

1 animal per dose rate (male animals were dosed at 1260, 3160 and 7940 mg/kg; female animals were dosed at 2000 and 5010mg/kg).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed once daily, the weight change 5 days after dosing was recorded
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

Satistical analysis was not performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LDLo

Effect level:

> 2 000 - < 3 160 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed at doses >2000 mg/kg (mortality at 3160, 5010 and 7940 mg/kg)

Clinical signs:

other: Toxic signs included reduced appetite and activity (two to four days in survivors), gradually increasing weakness, collapse (for period of 1 to 3 days), and death.

Gross pathology:

At autopsy there was lung congestion, liver discoloration, discoloration of kidneys and spleen, enlarged gall bladder, and gastrointestinal inflammation. Surviving animals were sacrificed at 14 days after dosing. Macroscopic examination revealed slight discoloration of kidneys.

Any other information on results incl. tables

Mortality and Weight Change

Animal No. - Sex	Weight (kg)	Dose (mg/kg)	Weight Change  (5 days after dosing)	Fate
1-Male	2.4	1260	-0.1	Survived
2-Female	2.7	2000	-0.1	Survived
3-Male	2.5	3160	-0.5	Died – 12 days
4-Female	2.6	5010	-0.4	Died – 12 days
5-Male	2.5	7940	-0.5	Died – 10 days

 

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The Acute Skin Absorption Minimal Lethal Dose for male and female rabbits was found to be > 2000 mg/kg and < 3160 mg/kg.

Executive summary:

Undiluted DMOP was applied at 1260, 2000, 3160, 5010 and 7940 mg/kg (one animal per dose rate (male animals were dosed at 1260, 3160 and 7940 mg/kg; female animals were dosed at 2000 and 5010mg/kg) to the closely clipped, intact skin of New Zealand white male and female rabbits. The treated areas were covered with plastic strips and the animals held in wooden stocks for periods up to 24 hours, after which time they were assigned to individual cages. Observations were made for toxic signs and the viscera of the test animals were examined macroscopically.

Toxic signs included reduced appetite and activity (2 to 4 days in survivors), gradually increasing weakness, collapse (for period of 1 to 3 days) and death. Body weight changes at 5 days post-dose were 0.1, 0.1, 0.5, 0.4 and 0.5 kg at dose rates of 1260, 2000, 3160, 5010 and 7940 mg/kg, respectively. At autopsy there was lung congestion, liver discoloration, discoloration of kidneys and spleen, enlarged gall bladder and gastrointestinal inflammation. Surviving animals were sacrificed at 14 days after dosing. Macroscopic examination revealed slight discoloration of kidneys. The acute skin absorption Minimal Lethal Dose for male and female rabbits was found to be > 2000 mg/kg and < 3160 mg/kg.