Ethyltriphenylphosphonium acetate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 126 mg/kg bw, OECD Guideline 401; RL2

 

Acute inhalation toxicity: exposure consideration; no testing required 

 

Acute dermal toxicity: LD50 1437 mg/kg bw, OECD Guideline 402

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

study conducted before imlementation of GLP

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Chemical name as given in report: Ethyltriphenylphosphonium acid acetate

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: 200 - 266 g
- Fasting period before study: 18 h
- Housing: in groupsin wire mesh cages

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1% (50 % for highest dose group)

Doses:

21.5, 46.4, 100, 215, 464 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequent intervals during the day of dosage, once daily thereafter
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

moving average method (Horn, H. J., 1956, Biometrics 12 (3): 311-322)

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

126 mg/kg bw

Based on:

test mat.

95% CL:

>= 92.6 - <= 171

Mortality:

yes

Clinical signs:

other: 21.5 mg/kg: all rats exhibiting mucoid diarrhea stains and one rat exhibiting bloody stains around the nose late in the dosage day. 46.4 mg/kg: one rat exhibiting slight diarrhea at the initial observation of the day of dosage. Four rats exhibited mucoid

Gross pathology:

Gross necropsy findings of the rats that died at the 0.100 gm/kg, 0.215 gm/kg, and the 0.464 gm/kg levels included externally evidence of excessive salivation stains in seven rats, diarrhea stains in six rats, and bloody stains around the nose and eyes of one rat.
Internally, all rats exhibited congested kidneys, ten rats exhibited congested adrenals, and six rats exhibited congested lungs. A clear to yellowish fluid resembling sample was found in the stomach or gastrointestinal tracts of all eleven rats, five of which exhibited a thickened pyloric region of the stomach, and three of which exhibited distended stomachs. Eight rats also exhibited irritated gastrointestinal tracts, including five which exhibited diffuse irritated areas in the small intestine. Six rats exhibited irritated peritoneal walls of which four of the peritoneal walls were wrinkled. One rat exhibited a pale liver where in contact with the stomach. Advanced autolysis was noted in four rats. No other gross pathological alterations were noted.

Gross necropsies performed at termination revealed three rats exhibiting slightly congested adrenals. No other significant gross pathological alterations were noted.

Dose	Conc.	Time of death
mg (kg bw	%	Hours				Days
		0.5 – 1	2	3-4	24	2	3	4	5	6	7-14
21.5	1	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5
46.4	1	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5	0/5
100	1	0/5	0/5	0/5	1/5	1/5	1/5	1/5	1/5	1/5	1/5
215	1	0/5	0/5	2/5	5/5
464	50	5/5

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 of Ethyltriphenylphosphonium acid acetate in male rats was 126 mg/kg bw.

Executive summary:

In an acute oral toxicity study comparable to OECD guideline 401, 5 male fasted rats were given a single oral dose of Ethyltriphenylphosphonium acid acetate in distilled water by gavage at doses of 21.5, 46.4, 100, 215 or 464 mg/kg bw and observed for 14 days.

5/5 animals in the highest dose died within the first hour. In the 215 mg/kg dose group, 2/5 rats died within 4 hours and 5/5 animals died within 24 hours. In the 100 mg/kg dose group, 1/5 animals died within 24 hours. Clinical signs shown by the animals found dead and surviving animals included mucoid diarrhea, comatose appearance, depression, depressed righting, placement, and pain reflexes, labored respiration, excessive salivation, and intermittent tremors.

 Gross necropsy findings of the rats that died at the 0.100 gm/kg, 0.215 gm/kg, and the 0.464 gm/kg levels included externally evidence of excessive salivation stains, diarrhea stains. All rats exhibited congested kidneys, ten rats exhibited congested adrenals, and six rats exhibited congested lungs. A clear to yellowish fluid resembling sample was found in the stomach or gastrointestinal tracts of all eleven rats, five of which exhibited a thickened pyloric region of the stomach, and three of which exhibited distended stomachs. Eight rats also exhibited irritated gastrointestinal tracts, including five which exhibited diffuse irritated areas in the small intestine. Six rats exhibited irritated peritoneal walls of which four of the peritoneal walls were wrinkled. One rat exhibited a pale liver where in contact with the stomach. Advanced autolysis was noted in four rats. No other gross pathological alterations were noted.

Gross necropsies performed at termination revealed three rats exhibiting slightly congested adrenals. No other significant gross pathological alterations were noted.

 The surviving animals had recovered from the symptoms between days 4 and 5. The average body weight gain of survivors was within the normal limits for the rats of the age, sex, and strain used in this study.

 

Oral LD50 (rat, males) 126 mg/kg bw

 

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

22 August 2017 - 17 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

other: designed as dose range finding study

Principles of method if other than guideline:

- Principle of test: The study was designed to provide information for further repeated dose toxicity studies.
- Short description of test conditions:
In the absence of any toxicity data, preliminary toxicity work was undertaken. Initially all of the preliminary toxicity work was performed using 0.5% Tween 80/1% Carboxy Methylcellulose as the vehicle. In this initial investigation animals mortalities occured at a dose of 1000 mg/kg bw. No clinical signs were evident at a dose of 500 mg/kg bw and below in male or female animals.

The test item was then administered by gavage to seven groups, of either two or three male and two or three female Wistar Han™:RccHan™:WIST strain rats, for up to fourteen consecutive days, at initial dose levels of 50 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle), 150 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle), 500 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle) and 500 mg/kg bw/day (with Distilled Water vehicle). Another dose group (150 mg/kg bw/day with Distilled Water vehicle) was added to the study following the early termination of both of the 500 mg/kg bw/day dose groups and a further dose group (100 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle) was added to the study following the early termination of both of the 150 mg/kg bw/day dose groups. A control group of three males and three females was dosed with vehicle alone (0.5% Tween/1% Carboxy Methylcellulose).

- Parameters analysed / observed:
Clinical signs, body weight change, dietary intake and water consumption were monitored during the study. At termination, blood samples were taken for selected blood chemical analysis and all animals were subjected to a gross necropsy examination (including retention of selected tissues) at termination.

GLP compliance:

no

Remarks:

The study was conducted in a facility which operates in accordance with Good Laboratory Practice principles, however no claim of GLP compliance was intended nor is made for this dose range finding study.

Test type:

other: designed as dose range finding study

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 12 weeks
- Weight at study initiation: 286 to 390 g (males), 205 to 236 g (females)
- Housing: in groups of three by sex in solid floor polypropylene cages with stainless steel mesh lids
and softwood flake bedding
- Diet (e.g. ad libitum): pelleted diet (Rodent 2018C Teklad Global Certified Diet, Envigo RMS (UK)
Limited, Oxon, UK) , ad libitum
- Water (e.g. ad libitum): mains drinking water supplied from polycarbonate bottles attached to the
cage , ad libitum
- Acclimation period: at least five days

DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.5% Tween/1% Carboxy Methylcellulose or Distilled Water

Details on oral exposure:

For the purpose of this study the test item was prepared at the appropriate concentrations as a suspension in 0.5% Tween/1% Carboxy Methylcellulose and for selected dose levels, as a suspension in Distilled Water.
The test item was administered within two hours of it being formulated. It is assumed that the formulation was stable for this duration.

Doses:

initial sighting study:
0, 50, 150, 500, 1000

DRF:
0, 50, 100, 150, 500 mg/kg bw/day (actual dose received)
Remarks: formulation prepared using 0.5% Tween 80/1% Carboxy Methylcellulose
0, 150, 500 mg/kg bw/day (actual dose received) formulations prepared using Distilled Water as the vehicle

No. of animals per sex per dose:

3

Control animals:

yes

Remarks:

concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD100

Effect level:

1 000 mg/kg bw

Based on:

act. ingr.

Key result

Sex:

male/female

Dose descriptor:

LD100

Effect level:

500 mg/kg bw

Based on:

act. ingr.

Mortality:

mortality observed, treatment-related

Clinical signs:

other: effects observed, treatment-related

Gross pathology:

no effects observed

Mortality

Two females treated with 500 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle) were sacrificed in extremis due to adverse clinical signs on Day 1. One female treated with 500 mg/kg bw/day (with Distilled Water vehicle) was found dead following dosing on Day 1. The remaining animals from both of these treatment groups were terminated on Day 1 due to excessive dose level. All of these animals had gaseous distension of the stomach and a pale glandular region of the stomach at necropsy.

 

One male treated with 150 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle) was found dead on Day 11. At necropsy, this male also had gaseous distension of the stomach and a pale glandular region of the stomach. The remaining animals from both of the 150 mg/kg bw/day treatment groups were terminated on this day (treatment Day 8 for the Distilled Water group) due to excessive dose level. These animals did not show any macroscopic abnormalities at necropsy.

 

Clinical Observations

The females treated with 500 mg/kg bw/day (with 0.5% Tween/1% Carboxy Methylcellulose vehicle) that were sacrificedin extremison Day 1 showed splayed gait, respiratory pattern changes, prostration, clonic convulsions and ataxia. The remaining female from this treatment group had pilo-erection, hunched posture and ataxia whilst the males from this treatment group had decreased respiratory rate, hunched posture, ataxia and one male also had clonic convulsions and prostration. The animals treated with 500 mg/kg bw/day (with Distilled Water vehicle) showed pilo-erection, hunched posture and ataxia.

 

At 150 mg/kg bw/day (using both vehicles), animals of either sex showed episodes of increased

salivation.

At 100 and 50 mg/kg bw/day, animals of either sex showed instances of increased salivation.

Interpretation of results:

study cannot be used for classification

Conclusions:

The oral (gavage) administration of ethyltriphenylphosphonium acetate at dose levels of 1000 or 500 mg/kg bw resulted either in mortality on day 1 or the termination on day 1 due to excessive clinical signs.
At a dose of 150 mg/kg bw/day (repeated application) one male animal was found dead on day 11. The remaining animals from both of the 150 mg/kg bw/day treatment groups were terminated on this day (treatment Day 8 for the Distilled Water group) due to excessive dose level. These animals did not show any macroscopic abnormalities at necropsy.

LD50 (male/female) > 150 mg/kg bw and < 500 mg/kg bw

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1973

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

0, 125, 250, 500, 1000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were weighed the day following dosing and a t weekly intervals for two weeks thereafter .
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

95% CL:

210 - 420

Mortality:

yes
All animals that expired did so within three hours post-administration of the material.

Gross pathology:

The autopsy r e s u l t s of the surviving animals given the highest dosage were negative for any gross pathology.

Dose (mg/kg bw)	Mortality %
125	0
250	25
500	100
1000	100

Interpretation of results:

Category 3 based on GHS criteria

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Remarks:

used only to justify read-across for other endpoints

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: 5 - 8 weeks
- Weight at study initiation: 152 - 185 g (males), 135 - 156 g (females)
- Fasting period before study: overnight fasting immediately before dosing and for approx. two hours after dosing
- Housing: in groups of up to five in solidfloor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, U.K.)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 39 - 64
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20, 27.4, 37.5 mg/mL

MAXIMUM DOSE VOLUME APPLIED: constant dose volume of 10 mL/kg

Doses:

range finding study: 100, 250, 500, 1000, 2000 mg/kg bw

main study: males: 200, 274, 375 mg/kg bw, females: 200 mg/kg bw

No. of animals per sex per dose:

range findign study: 1 male + 1 female
main study: 5 males for low, mid and high dose; 5 females for low dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2, 4 h after dosing, subsequently once daily
- Frequency of weighing: day 0, 7, 14 or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The LD50 and 95% confidence limits of the test material for males were calculated using a probit method of Finney D.J. 'Probit Analysis' 1971, Cambridge University Press.

Preliminary study:

Animals treated with 500 to 2000 mg/kg bw were found dead during the day of dosing. Common signs of systemic toxicity noted were hunched posture, lethargy and decreased respiratory rate with additional signs of ataxia, coma, ptosis, laboured respiration and loss of righting reflex. Based on this information, dose levels of 200, 274 and 375 mg/kg bw were selected for the main study.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 229 - <= 393

Mortality:

1/5 males and 1/5 females died at 200 mg/kg bw, 1/5 males died at 274 mg/kg bw, 4/5 males died at 375 mg/kg bw. Deaths were noted four to six hours and one day after dosing.

Clinical signs:

other: Common signs of systemic toxicity noted in all dose groups were ataxia, hunched posture, lethargy and decreased respiratory rate. Additional signs of laboured respiration were noted in animals treated with 200 mg/kg. An isolated incident of splayed gait w

Gross pathology:

Common abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. Sloughing and/or haemorrhage or slight haemorrhage of the gastric mucosa was noted in males treated with 200 to 375 mg/kg bw that died during the study. Sloughing of the nonglandular epithelium of the stomach was noted at necropsy of males treated with 375 mg/kg bw and the female treated with 200 mg/kg that died during the study. Haemorrhage or slight haemorrhage of the small intestine was noted at necropsy of males treated with 274 or 375 mg/kg and the female treated with 200 mg/kg bw that died during the study.
No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 and 95% confidence limits of the test material were calculated to be 300 (229 - 393) mg/kg bw in males. No difference in toxicity was noted between male and female animals.

Executive summary:

This study was performed to assess the acute oral toxicity of Methyltriphenylphosphonium chloride in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guideline 401 (1987) and EU Method B1 (1992).

Following a range-finding study, three groups, each of five fasted male animals were given a single oral dose of test material administered as a solution/suspension in distilled water at dose levels of 200, 274 and 375 mg/kg bw. A further group of five fasted females was similarly treated at a dose level of 200 mg/kg bw to confirm that one sex is not markedly more sensitive to the test material. The

surviving animals were observed for fourteen days after the day of dosing. All animals were subjected to gross pathological examination.

Deaths were noted four to six hours after dosing and one day after dosing. Common signs of systemic toxicity noted were ataxia, hunched posture, lethargy and decreased respiratory rate with additional or isolated incidents of laboured respiration and splayed gait. Surviving animals recovered one or two days after dosing except for one female treated with 200 mg/kg which appeared normal throughout the study.

Surviving animals showed expected gain in bodyweight during the study.

Common abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. Additional abnormalities noted were sloughing and/or haemorrhage or slight haemorrhage of the gastric mucosa, sloughing of the non-glandular epithelium of the stomach and haemorrhage or slight haemorrhage of the small intestine. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

The acute oral median lethal dose (LD50) and 95% confidence limits of the test material were calculated to be 300 (229 - 393) mg/kg bw in males. No difference in toxicity was noted between male and female animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

126 mg/kg bw

Quality of whole database:

All results considered in a weight-of-evidence approach. Lowest available result has been considered relevant.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K. Ltd., Blackthorn, Bicester, Oxon, U.K. and Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 231 - 255 g (males), females 200 - 232 g (females)
- Fasting period before study: no
- Housing: individually during exposure period, in groups of five for the remainder of the study
- Diet (e.g. ad libitum): ad libitum (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Wi tham, Essex, U.K.)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 51-61
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 10% of total body surface
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with cotton wool moistened with distilled water to remove any residual test material
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: moistened with distilled water

Duration of exposure:

24 h

Doses:

males: 2000 mg/kg bw
females: 1414, 2000 and 2828 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days
- Frequency of weighing: day 0, 7, 17 or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

LD50 and 95% confidence limits of the test material for females only were calculated using the method of Litchfield and Wilcoxon (J. Pharmacol 96, 1949)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 437 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 618 - <= 3 338

Mortality:

3/5 females died at 1414 mg/kg bw, 1/5 males and 2/5 females died at 2000 mg/kg bw, 4/5 females died at 2828 mg/kg bw
Deaths were noted 1-2 days after dosing.

Clinical signs:

other: Incidents of systemic toxicity, mostly confined to decedents, included hunched posture, lethargy, ptosis and decreased respiratory rate. Isolated incidents of ataxia with or without splayed gait were a1 so noted in one male and one female treated with 200

Gross pathology:

Common abnormalities noted at necropsy induced abnormally red or haemorrhagic lungs, dark livers or patchy pallor of the liver, dark or pale kidneys and haemorhage of the small intestines. Isolated incidents of haemorrhage of the gastric mucosa or haemorrhage of the site of application were also noted in the 2000 mg/kg dose group. No abnormalities were noted at necropsy of surviving animals at the end of the study.

Other findings:

Very slight to well-defined erythema was elicited by the test material. Other adverse dermal reactions noted were necrosis, small superficial scattered scabs, hardened light brown-coloured scabs and glossy skin. These dermal reactions sometimes precluded accurate assessment of the erythema and oedema.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The dermal LD50 and 95% confidence limits of the test material were calculated to be 1437 (618-3338) mg/kg bw in females. There was no significant difference in toxicity to males or females.

Executive summary:

This study was performed to assess the acute dermal toxicity of Methyltriphenylphosphonium chloride in the Sprague-Dawley strain rat. The method followed that described in OECD Guideline 402 (1987) and EU method B3 (1992).

A group of ten animals (five males and five females) was given a single 24- hour semi -occluded dermal application to intact skin at dose level of 2000 mg/kg bw. A further two groups of females were similarly treated at dose levels of 1414 and 2828 mg/kg bw. The surviving animals were observed for fourteen days after the day of dosing. All animals were subjected to gross pathological examination.

The majority of deaths were noted 1-2 days after dosing. Two females treated with 2828 mg/kg were found dead at the 4-hour observation. Incidents of systemic toxicity, mostly confined to decedents, included hunched posture, lethargy, ptosis and decreased respiratory rate. Isolated incidents of ataxia with or without splayed gait were also noted in one male and one female treated with 2000 mg/kg bw. All other surviving animals treated with 2000 mg/kg bw appeared normal throughout the study. Evidence of irritation of the treated skin sites was also noted.

All surviving animals showed bodyweight gain during the study.

Common abnormalities noted at necropsy included abnormally red or hemorrhagic lungs, dark livers or patchy pallor of the liver, dark or pale kidneys and hemorrhage of the small intestines. Isolated incidents of hemorrhage of the gastric mucosa or hemorrhage of the site of application were also noted in the 2000 mg/kg bw dose group. No abnormalities were noted at necropsy of surviving animals at the end of the study.

The dermal LD50 and 95% confidence limits of the test material were calculated by the method of Litchfield and Wilcoxon to be 1437 (618-3338) mg/kg bw in females. There was no significant difference in toxicity to males or females.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 437 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 618 - <= 3 338

Mortality:

3/5 females died at 1414 mg/kg bw, 1/5 males and 2/5 females died at 2000 mg/kg bw, 4/5 females
died at 2828 mg/kg bw
Deaths were noted 1-2 days after dosing.

Clinical signs:

other: Incidents of systemic toxicity, mostly confined to decedents, included hunched posture, lethargy, pt osis and decreased respiratory rate. Isolated incidents of ataxia with or without splayed gait were a1 so noted in one male and one female treated with 20

Gross pathology:

Common abnormalities noted at necropsy induced abnormally red or haemorrhagic lungs, dark livers
or patchy pallor of the liver, dark or pale kidneys and haemorhage of the small intestines. Isolated i
ncidents of haemorrhage of the gastric mucosa or haemorrhage of the site of application were also n
oted in the 2000 mg/kg dose group. No abnormalities were noted at necropsy of surviving animals at
the end of the study.

Other findings:

Very slight to well-defined erythema was elicited by the test material. Other adverse dermal reactio
ns noted were necrosis, small superficial scattered scabs, hardened light brown-coloured scabs and
glossy skin. These dermal reactions sometimes precluded accurate assessment of the erythema and
oedema.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The dermal LD50 and 95% confidence limits of the test material were calculated to be 1437 (618-3338) mg/kg bw in females. There was no significant difference in toxicity to males or females.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 437 mg/kg bw

Quality of whole database:

guideline study, GLP

Justification for classification or non-classification

Based on the available relevant and reliable data Ethyltriphenylphosphonium acetate needs to be classified Cat 3 and labelled H 301 according to the CLP Regulation (EC) No 1272/2008 with respect to acute oral toxicity.

Based on the available relevant and reliable data Ethyltriphenylphosphonium acetate needs to be classified Cat 4 and labelled H 312 according to the CLP Regulation (EC) No 1272/2008 with respect to acute dermal toxicity.