4-phenylbenzophenone

Endpoint summary

Description of key information

In a reliable acute oral toxicity study the substance was administered to Wistar rats (3 animals/dose) by oral gavage at a dose level of 2000 mg/kg bw (single administration). The oral LD50 is greater than 2000 mg/kg bw based on no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination at the end of the 14 day post-dosing observation period.

In a reliable acute dermal toxicity study the substance was administered by a single dermal dose to Wistar rats (male/female) at 2000 mg/kg body weight for 24 hours. No mortality occurred. Scales and/or erythema maculate were noted for two females between Days 3 and 10. General erythema, erythema maculate, scales and/or scabs were seen in the treated skin-area of three females during the observation period. The body weight gain was similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination. The dermal LD50 value of the substance in Wistar rats was established to exceed 2000 mg/kg body weight.

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:

20 Jun 2017 - 06 Jul 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Sponsor and 20161118
- Expiration date of the batch:17 November 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:At room temperature protected from light
- Stability under test conditions:Yes, maximum temperature: 90°C
- Solubility and stability of the test substance in the solvent/vehicle:Not indicated

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 8 weeks old)
- Weight at study initiation: 153 to 169 g
- Housing: polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material
- Fasting of animals: Deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item
- Diet (e.g. ad libitum): Pelleted rodent diet ad libitum except during designated procedures
- Water (e.g. ad libitum): Municipal tap-water was freely available
- Acclimation period: 5 days before the commencement of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation)
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: as required by OECD test guidelines that dissolved the substance

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, macroscopic abnormalities

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Three out of six animals displayed hunched posture on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

Not applicable.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 is greater than 2000 mg/kg bw.

Executive summary:

In an acute toxicity study the substance was administered by oral gavage to two consecutive groups of three female Wistar rats at a dose level of 2000 mg/kg bw (single administration). The animals were observed for a period of 14 days post-dosing. There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination. The oral LD50 is greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient to address requirements.

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:

12 September 2017 - 26 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Appearance: White to off-white crystalline powder
Batch: 20161118
Purity/Composition: 99.74%
Test item storage: At room temperature protected from light
Stable under storage conditions until: 17 November 2017 (expiry date)

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Females were nulliparous and non-pregnant.
Age at the Initiation of Dosing: Young adult animals (approximately 11 weeks old) were selected.
Weight at the Initiation of Dosing: Males: 295 to 320 g. Females: 186 to 197 g.
Acclimitisation: 5 days.
Housing: Polycarbonate cages.
Actual daily mean temperature: 21 to 22°C
Actual daily mean relative humidity: 46 to 60%.
A 12 hour light/12 hour dark cycle was maintained.
Ten or greater air changes per hour with 100% fresh air (no air recirculation).
Food and water: Ad libitum.

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animals
- % coverage: 10% i.e. approximately 25 cm² for males and 18 cm² for females
- Type of wrap if used: Surgical gauze patch successively covered with aluminum foil and Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water or an appropriate vehicle
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Scales and/or erythema maculate were noted for two females between Days 3 and 10. General erythema, erythema maculate, scales and/or scabs were seen in the treated skin-area of three females during the observation period.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of the substance in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The potential toxicity of the substance was determined, when given by a single dermal dose. The study was conducted according to OECD No. 402 (1987) ''Acute Dermal Toxicity''. The substance was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours.  No mortality occurred. Scales and/or erythema maculate were noted for two females between Days 3 and 10. General erythema, erythema maculate, scales and/or scabs were seen in the treated skin-area of three females during the observation period. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the substance in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient to address requirements.

Justification for classification or non-classification

Based on the findings of a reliable acute oral and dermal toxicity study conducted on the substance, classification of the substance is not justified.