Dimethyl octadecylphosphonate

Endpoint summary

Description of key information

Acute toxicity oral: LD50 > 2000 mg/kg bodyweight (OECD 420)
Acute toxicity dermal: LD50 > 2000 mg/kg bodyweight (non-guideline)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-06-07 to 2006-08-04

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Strain: Sprague-Dawley CD (Crl: CD® (SD) IGS BR)
-Sex: Female (nulliparous and non-pregnant)
- Source: Charles River (UK) Ltd
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: bodyweights were in the range of 196 to 211 g on Day 0 (animals dosed at 2000 mg/kg bw)
- Housing: the animals were housed in groups of up to four*
- Diet: Certified Rat and Mouse Diet* (Code 5LF2) was available ad libitum (with the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing)
- Water (e.g. ad libitum): ad libitum*
- Acclimation period: The acclimatisation period was at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): target of 19 to 25°C**
- Humidity (%): target of 30 to 70%**
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 2 hours continuous light (06:00 to 18:00) and 12 hours darkness.

*The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
** Any occasional deviations from these targets were considered not to have affected the integrity of the study.

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

All animals were dosed once with dimethyl octadecylphosphonate (DMOP) by oral gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.

Doses:

single dose of 300 mg/kg or 2000 mg/kg

A single female was treated at 300 mg/kg. In the absence of toxicity at 300 mg/kg, another female was treated at 2000 mg/kg. In the absence of toxicity at 2000 mg/kg, an additional group of 4 females were treated at 2000 mg/kg.

No. of animals per sex per dose:

1♀ at 300 mg/kg
followed by 1♀ at 2000 mg/kg
followed by 4♀ treated at 2000 mg/kg (total of 5♀ at 2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were made at 0.5, 1, 2 and 4 hours after dosing and then daily for 14 days. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Other observation: Morbidity and mortality checks were made twice daily.

Statistics:

Statistical analysis was not performed.

Preliminary study:

Toxicity was not observed when one female animal was treated with a dose of 300 mg/kg DMOP and another female was treated at 2000 mg/kg. In the absence of toxicity at 2000 mg/kg DMOP, an additional group of 4 females were treated at 2000 mg/kg DMOP.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

91.1% dimethyl octadecylphosphonate

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None.

Individual Bodyweights and Bodyweight Changes - 300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	222	254	270	32	16

Individual Bodyweights and Bodyweight Changes - 2000 mg/kg

Dose Level (mg/kg)	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) at During Week
		0	7	14	1	2
2000	2-0 Female	196	223	247	27	24
	3-0 Female	207	230	247	23	17
	3-1 Female	211	232	255	21	23
	3-2 Female	210	239	254	29	15
	3-3 Female	205	232	257	27	25

 

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute oral median lethal dose (LD50) of DMOP in the female Sprague-Dawley CD strain rat was greater than 2000 mg/kg bodyweight.

Executive summary:

An acute oral toxicity study was performed according to OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method". Test material (91.1% dimethyl octadecylphosphonate (DMOP)) was administered to Sprague-Dawley CD strain female rats by oral gavage. Following a preliminary test in which there were no deaths at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored for 14 days after test material administration. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity. All animals showed expected weight gains in bodyweight and no abnormalities were observed at necropsy. The acute oral median lethal dose (LD50) of DMOP in the female Sprague-Dawley CD strain rat was greater than 2000 mg/kg bodyweight.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral toxicity:

In the key study (Mullaney, T. 2006) Dimethyl octadecylphosphonate was evaluated for its acute oral toxicity in the Sprague-Dawley strain female rat. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was estimated to be greater than 2000 mg/kg bodyweight (OECD 420).

Test method:

The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 420 "Acute Oral Toxicity – Fixed dose method" and a Klimisch score of 1 was allocated. The results may be used as a basis for classification and labelling under Regulation (EC) No 1272/2008.

The test material (91.1% dimethyl octadecylphosphonate) was administered to Sprague-Dawley CD strain female rats by oral gavage. Following a preliminary test in which there were no deaths at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored for 14 days after test material administration. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity. All animals showed expected weight gains in bodyweight and no abnormalities were observed at necropsy. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. Based on the results of this study Dimethyl octadecylphosphonate is not classified under Regulation (EC) No 1272/2008 for acute toxicity (oral).

 

Two further supporting studies are available (Cerven, DR., 1980 and Birch, MD. 1972). Whilst these studies were not performed according to the current guidelines and were allocated Klimisch scores of 2, the LD50 results of both studies are in agreement with the key study and support the non-classification of Dimethyl octadecylphosphonate.

Dermal toxicity:

Two studies were performed (Cerven, DR. 1980 and Birch, MD. 1972). These studies were not performed according to the current guidelines and were allocated Klimisch scores of 2. In the 1980 Cerven, DR. study which was similar to an OECD 402 (Acute dermal toxicity study) a limit test was performed in 2 male and 2 female rabbits and application of the test substance was to abraded skin covered with an occlusive dressing. In this study it was concluded that the dermal LD50 for dimethyl octadecylphosphonate was greater than 20 g/kg.

In the second non-guideline dermal toxicity study (Birch, MC. 1972) undiluted dimethyl octadecylphosphonate (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 5010 mg/kg). The treated areas were covered with occlusive dressings for up to 24 hours and the animals were observed for clinical signs for a period of 14 days (or until death). Rabbits treated at 3160, 5101 and 7940 mg/kg died between 10 and 12 days after application and it was determined that the LD50 was >2000 and <3160 mg/kg.

Taking into consideration the results from both of these studies, dimethyl octadecylphosphonate was not classified for acute toxicity (dermal) according to Regulation (EC) No 1272/2008.

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
2 supporting studies (Cerven, DR (1980) and Birch, MD (1972)) are available

Justification for classification or non-classification

Acute toxicity oral:

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required for acute oral toxicity based on the available data.

 

Acute toxicity dermal:

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required for acute dermal toxicity based on the available data.