Reaction mass of potassium ethyl octylphosphonate and diethyl octylphosphonate

Endpoint summary

Description of key information

Acute toxicity after single oral application was tested in female rats, which received up to 5,000 mg/kg bw. One female out of ten died at 630 mg/kg bw, 2 at 1,250 mg/kg bw, 3 at 1,800 mg/kg bw, 6 at 2,500mg/kg bw and all animals at 5,000 mg/kg bw. Observed clinical signs were abnormal breathing and crouched posture. The necropsy of the deceased females revealed red spots in the lungs, gastro-intestinal tract injected with blood vessels, red secretion from eyes and nose. These findings are considered to be mainly attributed to the irritant properties of the test substance. The LD50 value for acute oral toxicity was calculated to be 2,010 mg/kg bw. Due to the findings described above (LD50 oral in rats 2,010 mg/kg bw) Reaction mass of potassiumethyl octylphosphonate and diethyl octylphoshonate does not have to be classified as acute orally toxic.

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:

Apr 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study design equivalent to OECD 401 with sufficient reporting

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Remarks:

performed before GLP guidelines

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Hoe WISKf(SPF71)
- Source: Hoechst AG Kastengrund - SPF breed
- Weight at study initiation: 160-180 g (female); (mean = 168.9 g; s = ± 5.99; n = 50)
- Fasting period before study: 16 hours before and 2 hours after application
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water: Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Housing: in groups, in plastic cages, wood shavings

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% (w/v)

Doses:

630 mg/kg bw
1250 mg/kg bw
1800 mg/kg bw
2500 mg/kg bw
5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations after application / Weighing once weekly
- Necropsy of survivors performed: yes

Statistics:

Probit analysis (method by Linder and Weber);
Confidence limits according to Fieller

Preliminary study:

Preliminary experiments showed higher sensitiveness for females. Therefore only females were used for the main study.

Sex:

female

Dose descriptor:

LD50

Effect level:

2 010 mg/kg bw

95% CL:

> 1 510 - < 2 790

Mortality:

Sex: female, Dose: 630 mg/kg bw, Mortality rate: 1 / 10
Sex: female, Dose: 1250 mg/kg bw, Mortality rate: 2 / 10
Sex: female, Dose: 1800 mg/kg bw, Mortality rate: 3 / 10
Sex: female, Dose: 2500 mg/kg bw, Mortality rate: 6 / 10
Sex: female, Dose: 5000 mg/kg bw, Mortality rate: 10 / 10

Clinical signs:

other: Mortally poisened animals died within 2 h -4 days after application. Following symptoms were observed: abnormal breathing, crouched posture Surviving animals showed no symptoms.

Gross pathology:

Dissection of rats killed at the end of the observation period revealed no macroscopic findings.
Necropsy of the deceased animals revealed following macroscopic findings: red spots in the lungs, gastro-intestinal tract injected with blood vessels, red secretion from eyes and nose

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of Reaction mass of potassium ethyl octylphosphonate and diethyl octylphoshonate was 2010 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.

Executive summary:

Reaction mass of potassium ethyl octylphosphonate and diethyl octylphosphonate was tested for its acute oral toxicity potential. 10 female rats were treated with doses of 630, 1250, 1800, 2500 or 5000 mg/kg bw and observed for 14 days.

The median lethal dose of Reaction mass of ethyl octylphosphonate and diethyl octylphosphonate (LD50) was 2010 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 010 mg/kg bw

Quality of whole database:

2 (reliable with restrictions)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Based on the results of an oral toxicity study the LD₅₀value for acute oral toxicity was calculated to be 2,010 mg/kg bw.
In accordance with REACH “Column 2” in Annex VIII there is sufficient weight of evidence from several independent sources of information leading to the conclusion that Reaction mass of potassium ethyl octylphosphonate and diethyl octylphosphonate does not exert systemic toxic effects after acute inhalation exposure and thus does not have to be classified, because
- the LD50 value for acute oral toxicity of Reaction mass of ethyl octylphosphonate and diethylphosphonate is 2010 mg/kg bw, and
- exposure of humans via inhalation is considered unlikely taking into account the vapour pressure (0.0093 Pa) and the physical form (paste) of the substance.
Therefore, and with reference to animal welfare it is concluded that testing of acute inhalation toxicity of Reaction mass of ethyl octylphosphonate and diethyl octylphosphonate is not scientifically necessary.

It can reasonably be deduced that Reaction mass of potassium ethyl octylphosphonate and diethyl octylphosphonate does not exert systemic toxic effects after dermal application and thus does not have to be classified, because the median lethal dose of this substance after administration of a single oral dose was found to be 2010 mg/kg bw in rats. Due to the combination of its polar (ionic) character and the long extent of the alcoholic chain it is unlikely that higher amounts (limit dose of dermal toxicity testing according OECD 402: 2,000 mg/kg bw/d) than tested in the acute oral toxicity study will be systemically available via the skin barrier even if the most unlikely amount of 100% penetration is assumed. Therefore, testing is not scientifically necessary.

Justification for selection of acute toxicity – oral endpoint
Study design equivalent to OECD 401 with sufficient reporting

Justification for classification or non-classification

Due to the findings described in the acute oral toxicity study (LD₅₀oral in rats 2,010 mg/kg bw Reaction mass of potassium ethyl octylphosphonate and diethyl octylphosphonate does not have to be classified as acute orally toxic. Based on the substance's physico-chemical properties no higher systemically exposure via inhalation or dermal penetration is expected to occur than that tested in the course of the oral toxicity study. Therefore, Reaction mass of potassium ethyl octylphosphonate and diethyl octylphosphonate does not have to be classified as acute toxic.