Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Remarks:
Homogenous Liquid
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)

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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.