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Description of key information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CFY strain rats supplied by Bantin & Kingman Ltd, Grimston, Aldborough, Hull, UK
- Age at study initiation: approximately five to eight weeks old
- Weight at study initiation: mean weights: males weighed 126 - 150g, and the females 120 - 142g,
- Fasting period before study: overnight immediately before dosing and for approximately two hours after dosing
- Housing: 5 by sex in solid-floor polypropylene cages with sawdust bedding; the animals were given a unique number within the study by ear punching and a number written on a cage card
- Diet: Rat and Mouse Expanded Diet No 1, Special Diet Services Ltd, Witham, Essex, UK; ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 46 - 60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50, 100, 300 and 500 mg/ml
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle: test substance administered as suspension
Doses:
5000 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 and weighing: animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation
- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.
- Other examinations performed: individual body weights were recorded on the day of treatment (day 0) and on days 7 and 14
Preliminary study:
Because no deaths occurred in the range-finding study, LD50 of the test substance was considered to be greater than 5000 mg/kg bw and the highest dose level was therefore used for the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: no mortality occured
Mortality:
no mortality
Clinical signs:
- Hunched posture, lethargy and piloerection were noted in all animals one and four hours after dosing.
- Decreased respiratory rate was also noted in all animals one hour after dosing.
- All animals appeared normal one day after treatment.
Body weight:
all animals showed expected gain in body weight over the study period (see table).
Gross pathology:
no abnormalities were noted at necropsy of animals (killed at the end of the study).

Mean body weights (g):

Males:

Time  5000 mg/kg bw group
 Day 0  137.6±9.6
 Day 7  170.8±11.6
 Day 14  216.2±12.5

Females:

Time  5000 mg/kg bw group
 Day 0  128.8±8.4
 Day 7  152.6±7.7
 Day 14  180.6±12.0
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
2011
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. 24th, 1987
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
May 30th, 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: app. 8 weeks, females: app. 12 weeks
- Weight at study initiation: males: 230.8g +/- 13.2g, females 204.8g +/- 3.1g
- Housing: single in Markolon type III cages
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, Altrip, Germany
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm²
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, using warm water
- Time after start of exposure: 24h, right after removal of the dressing

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5ml/kg b.w.
- Concentration (if solution): 40%
- For solids, paste formed:no (suspension)
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 exposure, once every workday thereafter
- Frequency of weighing: weekly, beginning on day 0
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, skin reactions according to Draize
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:
no mortality occured
Clinical signs:
no systemic toxicity was observed, local skin irritation was observed in 1 male and all females (details on severity in tables 1+2)
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
Mean body weight of the female animals did not adequately increase during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
no abnormalities

Table 1: Skin irritation males

Animal No.: R 40 R 41 R 42 R 43 R 44
Erythema grade 1: - - d7 - d10 - -
Erythema grade 2: - - d2 - d6 - -
Incrustations: - - d6 - d14 - -
Scaling: - - d6 - d7 - -

Table 2: Skin irritation females

Animal No.: R 45 R 46 R 47 R 48 R 49
Erythema grade 1: d1 - d6 d6 - d7 d8 - d14 d6 - d7 d3 - d6
Erythema grade 2: - d1 - d3 d1; d6 - d7 d1 - d3 d1 - d2
Erythema grade 3: - - d2 - d3 - -
Incrustations: - - d6 - d14 - -
Scaling: - d6 - d8 d6 - d14 d6 - d8 d6 - d7

d: day

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test substance after single dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

In two oral studies (BASF AG 1979, BASF Japan 1989), of which the latter was performed according to OECD 401 and GLP, no mortality occured in male or female rats after oral administration of up to 5000mg/kg b.w. via gavage. In the latter study hunched posture, lethargy, piloerection, and decreased respiratory rate were observed in all animals up to four hours after dosing. No further abnormalities were observed. Thus the oral LD50 is greater than 5000mg/kg b.w..

In an acute dermal toxicity study (Limit Test) according to OECD 402 and GLP (BASF SE 2011), 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 were observed in the animals. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The following test item-related local effects were recorded during the course of the study:

o Slight to moderate erythema (grade 1 to 3)

o Incrustations

o Scaling

Since no deaths occured, the dermal LD50 is greater than 2000mg/kg b.w.

In accordance with column 2 of REACH Annex VIII, no acute inhalation toxicity study was conducted as two other routes are provided.

Justification for classification or non-classification

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