Ethyltriphenylphosphonium acetate

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Test animals

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

Administration / exposure

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)

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.