Registration Dossier

Administrative data

Description of key information

LD50 oral (rat) > 5000mg/kg (BASF 1982, OECD 401)
LD50 dermal (rat) > 2000mg/kg (BASF 2013, OECD 402, GLP)
IRT: saturated vapour does not cause mortality within 7h
LD50 i.p. (rat) = 1470mg/kg (BASF 1982)

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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted May 1981
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Acclimatization period: at least one week.
Age of animals at beginning of study: About 12 weeks
Type of cage: Type DK-III stainless steel wire mesh cages
Number of animals per cage: 5
Animal identification: Identification of groups using cage cards
Room temperature: 20 - 26°C
Relative humidity: 45 - 75%
Air changes: 15 - 20 /hour
Day/night rhythm: 12 h/12 h (6.00 - 18.00 hours/18.00 - 6.00 hours)
Drinking water: Fully demineralized water each workday, ad libitum; tap water on public holidays, ad libitum
Diet: SSNIFF R; Ssniff Versuchstierdiäten, Soest, FRG
Fasting period: 16 hours before administration, water available ad libitum
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% in water
Details on oral exposure:
Preparation with 0.5% aqueous carboxymethyl cellulose
Reason for the vehicle: Aqueous formulation corresponds to the physiological medium
Form of administration: Emulsion
Concentrations used: 26.1, 38.3, 50% (w/v)
Application volume: 10 ml/kg
Doses:
2610, 3830, 5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observation period: 14 days
Weight check: Animals of comparable weights (± 20 g) in one cage.
Cageside observation: Recording of signs and symptoms < 15', 15', 30', 1 h, 2 h, 4 h, and 5 h after administration of test substance and then once each workday. Check for moribund and dead animals twice each workday and once daily at weekends and on public holidays.
Pathology: Withdrawal of feed 16 hours before sacrifice with CO2, followed by necropsy and gross-pathological examination. All animals that die are necropsied as early as possible.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: Mortality occurred at all dose levels (2160, 3830 and 5000 mg/kg )
Mortality:
Males: 5000 mg/kg 1/5 after 1 day, no mortality at other dose levels
Females: 5000 and 2610 mg/kg: 2/5 after 1 day, 3830 mg/kg: 1/5 after 1 day
Clinical signs:
Male animals:
All dose groups showed dyspnea, apathy, staggering, twitching, piloerection (not observed for high dose males), and poor general state.
Abnormal position, tonus with bending, tonic-clonic convulsions, salivation, and fasciculation were observed in high dose males only.

Female animals:
The following symptoms were observed in all dose groups, unless noted otherwise: Dyspnea, apathy, abnormal position (not in mid dose females), staggering, paresis hind leg (only low dose), twitching, spastic gait (only low dose), tonus with bending, , tonic convulsions (not in mid dose females), clonic convulsions (only low dose), piloerection, erythema (only low dose), fasciculation (not in mid dose femaes), cachexia (only low dose), and poor general state
Additionally high dose females showed opisthotonos, loss of hair, exsiccosis, and salivation.

Most symptoms were only observed for app. 1 day (2 days in high dose animals), but low dose females exhibited dyspnea, apathy, staggering, and poor general state up to day 12 or 13.
Body weight:
Mean body weight male animals: 193 at study start, 282 g after 13 days
Mean body weight female animals: 190 g at study start, 224 g after 13 days
Gross pathology:
Animals that died (female): Stomach: Bloody erosions in the region of the glandular stomach in 1 animal; liver: grayish-white to clay-colored periphery involving a minimum part of the acinus.
Sacrificed animals (male & female): Organs: No abnormalities detected.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the acute oral LD50 of the registered substance was found to be >5000 mg/kg bw in the rat.
Executive summary:

Males were less sensitive than females. Doses of 2160, 3830 and 5000 mg/kg bw were tested. In females, 2 of 5 animals each died at 2160 and 5000 mg/kg bw within the first day of dosing. In the mid dose, one female died. One high dose male died, but no mortality was observed in the remaining dose groups. In the females that died, bloody erosions in the region of the glandular stomach occurred in 1 animal. In the liver, grayish-white to clay-colored periphery involving a minimum part of the acinus was observed. No findings were observed in surviving animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was performed in principle as described in OECD test guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20°C. Young adult laboratory rats, 3 males and 3 females per experiment, were exposed to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 h. Since the substance is UV light sensitive, the experiment was performed in the dark. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 14 day study period.
GLP compliance:
no
Test type:
other: inhalation risk test
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Three animals per cage; type: wire cage (Becker, D III)
Identification of animals: Toe amputation
Age at start of study: 8 - 9 weeks
Acclimatization period: At least 5 days
Weight of animals at start of study: males 293 g, females 233 g (on average)
Animal housing / room temperature: 22 ± 2°C
Relative humidity: 55 ± 5%
Illumination day/night rhythm: 12 h/12 h (6.00 - 18.00 hours light, 18.00 - 6.00 hours dark)
The animals received SSNIFF R complete diet for rats and mice, supplied by SSNIFF Versuchstierdiäten GmbH, Soest, FRG, in the form of pellets ad libitum and about 250 ml/cage tap water daily.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Remarks on duration:
14 day observation period
Concentrations:
no substance loss could be determined over the course of the experiment. Based on the saturated vapour pressure, the saturated vapour concentration can be calculated to be 2.7e-5 mg/l.
No. of animals per sex per dose:
6 (3 per sex each in 2 independent experiments)
Control animals:
no
Details on study design:
Clinical signs and mortality of the animals were recorded each workday and daily, respectively. The animals that died or those sacrificed with carbon dioxide at the end of the post-exposure observation period were subjected to a gross-pathological examination.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 0 mg/L air
Based on:
other: calculated (equals saturated vapour concentration)
Exp. duration:
7 h
Mortality:
None
Clinical signs:
other: No abnormalities detected.
Gross pathology:
No abnormalities detected.
Interpretation of results:
study cannot be used for classification
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted Feb. 1987
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, 97633 Sulzfeld, Germany
- Age at study initiation: males: app. 8 weeks, females app. 12 weeks
- Weight at study initiation: males: 229g, females 208g, on average
- Fasting period before study: no
- Housing: single in Makrolon type III cages
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: at least 10% of total body surface
- Type of wrap if used: 4 layers of absorbent gauze and stretch bandage (Fixomull® Stretch (adhesive fleece)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water after removal of the dressing
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.77ml/kg
Duration of exposure:
24h
Doses:
2000mg/kg b.w.
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: several times on the day of administration, daily thereafter
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: Scoring of skin findings according to Draize 30-60minutes after removal of the dressing
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality occured
Mortality:
none
Clinical signs:
none
Body weight:
expected increase
Gross pathology:
no abnormalities detected
Other findings:
no local effects
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test the acute dermal LD50 of the registered substance was found to be ≥2000 mg/kg bw in the rat.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

In an acute oral toxicity study (BASF 1982), 5 male and 5 female fasted Wistar rats per group were given a single oral dose of 2610, 3830, or 5000mg/kg of ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate in 0.5% aqueous CMC by gavage. The animals were observerd for 14 days and a necropsy was performed. One high dose male died within 1 day. Mortality was observed for females in all dose groups, i.e. 2/5 low and high dose animals and 1 mid dose animal died within 1 day. Signs of toxicity were mostly observed on the first day after administration, except for high dose males and females and low dose females, where signs persisted longer. During necropsy, bloody erosions in the region of the glandular stomach were observed in one female that died. All females that died showed a liver with grayish white to clay colored periphery. In the animals sacrificed at the end of the study, no abnormalities were detected. The oral LD50 value for this substance is thus greater than 5000mg/kg b.w. for males and females.

In an acute dermal toxicity study (Limit Test) according to OECD 402 and GLP (BASF SE 2013), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No signs of systemic toxicity or local irritation were observed. The mean body weight increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Thus, the dermal LD50 is greater than 2000mg/kg b.w.

After i.p. exposure to 215, 681, 1000, 1470, and 2000mg/kg b.w. of the test substance in 0.5% aqueous CMC, the LD50 in rats was determined to be 1470mg/kg b.w. (BASF 1982). All of the 5 male and 5 female Wistar rats exposed 2000mg/kg, and 4 of the 10 animals exposed to 1470mg/kg died within 1 or 2 days. No mortality occured in the remaining dose groups. Clinical signs were observed for a maximum of 2 h in the two lowest dose groups, up to about 1 day in the mid dose animals, and for several days or until death in the two highest dose groups. Gross pathology revealed precipitates of the test substance in the animals that died, and rounded lobes and adhesion of lobes in the liver, as well as adhesions of liver, stomach and spleen and milky coatings on liver, spleen, and kidneys.

No mortality occured in an inhalation hazard test, in which 6 male and female Sprague-Dawley rats were exposed to the saturated vapour concentration for 7h in two independent experiments and observed for 14 days. No mortality, clinical signs, or abnormalities at necropsy were detected. Due to the low vapour pressure the concentration in air has been calculated as 2.7e-5mg/l.

Justification for classification or non-classification

Based on the results of the available studies, ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate is not required to be classified for its acute toxicity potential according to 67/548/EEC and CLP/EU-GHS requirements.