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Description of key information

The acute oral test available on Trihexyltetradecylphosphonium chloride (CAS no 258864-54-9) indicates GHS classification as acute oral toxicity category 4 (LD50 between 300 and 2000 mg/kg). The oral LD50 study on Trihexyltetradecylphosphonium chloride (CAS no 258864-54-9) was performed according to OECD Guideline 423 and conformed with GLP requirements. This study was considered reliable without restrictions (Klimisch 1).

The acute dermal test available on Trihexyltetradecylphosphonium chloride (CAS no 258864-54-9) indicates a classification as not classified (LD50 > 2000 mg/kg). The dermal LD50 study on Trihexyltetradecylphosphonium chloride (CAS no 258864-54-9) was performed according to OECD Guideline 402 and conformed with GLP requirements. This study was considered reliable without restrictions (Klimisch 1).

No data is available on acute toxicity via inhalation route.

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:
2015-03-27 - 2015-05-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
Trade name: CYPHOS IL 101 Phosphonium Salt
Physical state: liquid
Composition of test material, percentage of components: Trihexyl(tetradecyl)phosphonium chloride (258864-54-9), > 95%
Lot/batch No.: WEC031280
Expiration date of the lot/batch: >1 year (March 2016) when stored at room temperature and protected from direct contact with water (hydrophobic)
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Stone Ridge NY, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Approx. 9 weeks old
- Weight at study initiation: 201 - 302 g for males and 197 - 220 for females; the weight variation did not exceed 20%
- Fasting period before study: Animals were deprived of food for 16-20 hours prior to dosing.
- Housing: housed in suspended wire cages; 5/sex/cage prior to dosing and 3/sex/cage following dosing; containing absorbent paper as bedding material.
- Diet: Fresh PMI Rat Chow (Diet #5012); ad libitum except just prior to dosing
- Water; ad libitum; tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled temperature
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test article was used as received.

MAXIMUM DOSE VOLUME APPLIED: 2000 ml/kg
Doses:
Females: 300 and 2000 mg/kg bw
Males: 300 mg/kg bw
No. of animals per sex per dose:
- 300 mg/kg bw: 3 females and 3 males
- 2000 mg/kg bw: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was observed twice daily. The time of death was recorded as precisely as possible. Body weights were measured on Days 1 (pre-administration), 8, at death and on Day 15 in the survivors. Clinical signs were observed at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
No statistical analysis was performed.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived following a single 300 mg/kg bw oral dose.
All three females died on Day 1 or Day 5 following a single 2000 mg/kg bw oral dose.
Clinical signs:
300 mg/kg bw: Abnormal physical signs including chromorhinorrhea, yellow staining, localized hair loss, soiling, and wetness of the anogenital area, few feces, chromodacryorrhea, unkempt appaerence, and piloerection were observed.
2000 mg/kg bw: Prior to death, abnormal physical signs including chromorhinorrhea, soiling, yellow staining, localized hair loss, and wetnes of the anogenital area, few feces, piloerection, chromodacryorrhea, dyspnea, lethargy, and flaccid muscle tone were observed.
Body weight:
300 mg/kg bw (females/males): All six animals gained body weight by study termination; one animal lost weight from Day 0 to Day 7.
2000 mg/kg bw (females): Terminal body weight loss was observed among all three animals.
Gross pathology:
300 mg/kg bw (females/males): Hair loss on the anogenital area was found at macroscopic post mortem examination of two females that survived until termination. No abnormalities were found at macroscopic post mortem examination of one female and all three males that survived until termination.
2000 mg/kg bw (females): The gross necropsy revealed localized hair loss, yellow and brown staining, soilin, and wetness of the anogenital area, chromodacryorrhea, chromorhinorrhea, brown staining of the nose/mouth area, and abnormalities of the gastrointestinal tract.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 300 mg/kg but less than 2000 mg/kg body weight.
Executive summary:

A GLP-compliant acute toxicity study according to OECD Guideline 423 was conducted. A group of 3 female Sprague Dawley rats was given a single oral dose of Trihexyltetradecylphosphonium chloride at 300 mg/kg bw. An additional three healthy males were dosed as a confirmatory group at 300 mg/kg bw. Three additional healthy females were dosed at 2000 mg/kg. The rats were observed for 14 days.

300 mg/kg: All three females and males survived following a single 300 mg/kg oral dose. Abnormal physical signs were observed and all six animals gained body weights by study termination; one animal lost weight from Day 0 to Day 7. The gross necropsy revealed hair loss on the anogenital area.

2000 mg/kg: All three females died, on Day 1 or Day 5, following a single 2000 mg/kg oral dose. Prior to death, abnormal physical signs were observed. Terminal body weight loss was observed among all three animals. The gross necropsy revealed hair loss, yellow and brown staining, soiling, and wetness of the anogenital area, chromodacryorrhea, chromiorhinorrhea, brown stainig of the nose/mouth area, and abnormalities of the gastrointestinal tract.

In conclusion, the oral LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 300 mg/kg but less than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-03-27 - 2015-05-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Trade name: CYPHOS IL 101 Phosphonium Salt
Physical state: liquid
Composition of test material, percentage of components: Trihexyl(tetradecyl)phosphonium chloride (258864-54-9), > 95%
Lot/batch No.: WEC031280
Expiration date of the lot/batch: >1 year when stored at room temperature and protected from direct contact with water (hydrophobic)
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Stone Ridge, NY
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 250-278g for males and 204-222g for females; the weight variation did not exceed 20% of the mean weight
- Housing: individually housed in suspended wire cages
- Diet: Fresh PMI Rat Chow provided daily
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature-controlled room
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Prepared site was ca. 10% of the body surface
- Type of wrap if used: The test material was held in contact with the skin by a porous gauze dressing. The torso was wrapped with a piece of porous dressing to retain the gauze dressing and porous non-irritating tape encircled the entire trunk of the aniaml.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed by wiping with dry gauze.
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.43 - 0.59 ml (to achieve 2000 mg/kg)
Duration of exposure:
24 hours
Doses:
2000 mg/lg
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 and weighing: The animals were observed for physical signs at 1 and 4 hours postdose and once daily for 14 days. Body weights were recorded pretest, weekly and at termination.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All ten rats survived the 2000 mg/kg 24-hour dermal exposure.
Clinical signs:
Abnormal physical signs including brown staining of the nose/mouth area, partially chewed food in pan liner, unkempt appearance, localized hair loss (inside of hind legs and on abdomen), prolapsed penis, chromorhinorrhea, and chromodacryorrhea were observed.

Dermal observations:
At 24 hours post-dosing, erythema was absent to severe and edema was slight to moderate; pale and dark areas were observed. By Day 14, erythema was absent to severe and edema was absent; moderate to severe eschar formation, necrotic and flaking skin, shiny areas and poor hair regrowth were observed.
Body weight:
All animals gained weight by study termination.
Gross pathology:
The gross necropsy revealed prolapsed penis, localized hair loss (inside hind legs and on abdomen), chromorhinorrhea, and unkempt appearance.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of the test material was greater than 2000 mg/kg bw in rats.
Executive summary:

A GLP-compliant acute toxicity study according to OECD Guideline 402 was conducted. Three male and 3 female Sprague Dawley rats were exposed to a single dose of Trihexyltetradecylphosphonium chloride at 2000 mg/kg bw. The rats were observed for 14 days.

Abnormal physical signs including brown staining of the nose/mouth area, partially chewed food in pan liner, unkempt appearance, localized hair loss (inside of hind legs and on abdomen), prolapsed penis, chromorhinorrhea, and chromodacryorrhea were observed.

Dermal observations:

At 24 hours post-dosing, erythema was absent to severe and edema was slight to moderate; pale and dark areas were observed. By Day 14, erythema was absent to severe and edema was absent; moderate to severe eschar formation, necrotic and flaking skin, shiny areas and poor hair regrowth were observed.

In conclusion, the dermal LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

One study is available for acute oral toxicity of Trihexyltetradecylphosphonium chloride in rats. This study was performed according to the acute toxic class method (OECD guideline 423) and conformed with GLP requirements. In this study, trihexyltetradecylphosphonium chloride was administered to rats by oral gavage. The oral LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 300 mg/kg but less than 2000 mg/kg body weight. This study is considered reliable (Klimisch 1) and is the key study for endpoint coverage.

One study is available for acute dermal toxicity of Trihexyltetradecylphosphonium chloride in rats. This study was performed according to the OECD guideline 402 and conformed with GLP requirements. In this study, trihexyltetradecylphosphonium chloride was administered to rats at a single limit dose of 2000 mg/kg. The dermal LD50 value of Trihexyltetradecylphosphonium chloride in Sprague Dawley rats was established to be greater than 2000 mg/kg body weight. This study is considered reliable (Klimisch 1) and is the key study for endpoint coverage.

Justification for classification or non-classification

Justification for selection of acute toxicity – oral endpoint

Trihexyltetradecylphosphonium chloride (CAS No 258864-54-9) is classified for acute oral toxicity Category 4 based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.

Trihexyltetradecylphosphonium chloride (CAS No 258864-54-9) is not classified for acute dermal toxicity based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.