Ethyltriphenylphosphonium iodide

Endpoint summary

Description of key information

Oral: LD50 (rat, m/f) >25 - <200 mg/kg bw (OECD 423/EU B.1 tris, GLP)

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:

2003-01-28 to 2003-02-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

June 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: males 219-357 g, females 164-217 g
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: 3 animals/sex/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): app. 15
- Photoperiod (hrs dark / hrs light): 12/12
Deviations from the maximum level for relative humidity (with a maximum of 20%) occurred which might have been caused by cleaning procedures in the room. Based on laboratory historical data these deviations were considered not to have affected the study integrity.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

Vehicle:
- 1% Aqueous carboxymethyl cellulose. The vehicle was selected based on trial formulations performed at study laboratory.

The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable Ievel. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

25, 200 and 2000 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw: 3 females
200 and 25 mg/kg bw: 3 per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality twice daily. Animals were weighed on Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1). Animals were observed for clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross necropsy

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 25 - < 200 mg/kg bw

Based on:

test mat.

Mortality:

The incidence of mortality was as follows, presented in chronological order of treatment:
Dose Ievel Mortality Sex
2000 mg/kg 2/3 females
200 mg/kg 1/3 females
200 mg/kg 2/3 males
25 mg/kg 0/3 males
25 mg/kg 0/3 females

Clinical signs:

other: Clinical signs observed during the study period were as follows: Dose Ievel Clinical signs 2000 mg/kg Hunched posture, lethargy, uncoordinated movements, laboured respiration, red staining, chromodacryorrhoea 200 mg/kg

Gross pathology:

At macroscopic post mortem examination small and large intestines distended with gas was found among the animals that died at 2000 mg/kg and red discolouration of the glandular mucosa was found in the male that died at 200 mg/kg. Macroscopic post mortem examination of the other animals that died during the study and of the surviving animals at termination did not reveal any abnormalities.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Oral LD50 25-200 mg/kg bw; acute oral toxicity category 2 based on the criteria of REGULATION (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

25 mg/kg bw

Quality of whole database:

Data from a GLP compliant guideline study with reliability 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study according to OECD guideline 423, 1996, EU method B.1 tris, 1996 and US EPA Guideline OPPTS 870.1100, 1996, initially, Ethyltriphenylphosphonium iodide was administered by gavage to three female Wistar rats at 2000 mg/kg bw. In a stepwise procedure additional groups of female and male animals were dosed at 200 and 25 mg/kg bw. In the dose groups 2000, 200 and 25 mg/kg bw, 2/3, 3/6 (1/3 females, 2/3 males) and 0/6 animals died, respectively. Clinical signs observed during the study period were at dose level 2000 mg/kg bw hunched posture, lethargy, uncoordinated movements, laboured respiration, red staining and chromodacryorrhoea, at 200 mg/kg bw hunched/flat posture, uncoordinated movements, quick/slow breathing, piloerection, chromodacryorrhoea, lethargy and diarrhoea and at 25 mg/kg bw hunched posture, piloerection, lethargy and chromodacryorrhoea. The surviving animals had recovered from the symptoms between days 2 and 13. The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. At macroscopic post mortem examination small and large intestines distended with gas was found among the animals that died at 2000 mg/kg bw and red discolouration of the glandular mucosa was found in the male that died at 200 mg/kg bw. Macroscopic post mortem examination of the other animals that died during the study and of the surviving animals at termination did not reveal any abnormalities.

Oral LD50 (rat, m/f) >25 - <200 mg/kg bw

 

In a supporting study similar to OECD guideline 401 with albino rats (strain not mentioned) an oral LD50 of 79.4 mg/kg bw (95% confidence limits 58.4 - 108 mg/kg bw) was determined.

Justification for classification or non-classification

Oral LD50 Wistar rat > 25 < 200 mg/kg bw; acute oral toxicity category 2 based on the criteria of REGULATION (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

Ethyltriphenylphosphonium iodide is not classified for inhalative and dermal acute toxicity because of lacking data.