4,4'-bis(diethylamino)benzophenone

Acute Toxicity: dermal

Administrative data

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

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The following functional groups are common across the target and source substance: aryl groups and carbonyl groups. It is the scientific hypothesis of this read-across justification that the presence of these functional groups dictates the toxicological potential of the target substance. The target and sources substances both pass Lipinski’s rule of five and are therefore considered to have the potential to be absorbed into the body via the oral route. The breakdown products within the body are likely to be similar, or the same, as shown in the table below.
Breakdown products:
Source substance - Benzophenone, Toluene, Hippuric acid or ortho-Cresol
Target substance - Benzophenone, Diethylamine (x2)

The target and source substance are expected to degrade in a similar way within the body and are expected to generate similar if not the same major metabolites. The molecular weight of the target and source substance are similar and are both below 500 daltons. The water solubility and partition coefficients of the target and source substances are comparable. Both the target and source substances pass Lipinski’s rule of five indicating that they may be orally absorbed and therefore are available within the body and may act in a similar toxic way.


2. SOURCE AND TARGET CHEMICAL
The source and target substances are composed of the same functional groups bound together in similar ways. The molecular weight of the target and source substances are similar and they are expected to be absorbed in the body in similar ways. The breakdown products of the substance are expected to be the same or very similar and are expected to have the same potential for acute toxicity.
The target and source substance contains very low levels of unidentified impurities. These impurities are considered not to affect the classification and labelling of the substance due to the very low levels at which they occur. No information on impurities present in the source test materials was available in the literature sources.
The impact of “impurities” is therefore considered not to affect the reliability of the read-across prediction.


3. ANALOGUE APPROACH JUSTIFICATION
Due to the similarities of the source and target substance with regards to physico-chemical properties, Lipinski’s rule of 5, and the fact that the target substance is expected to breakdown into structurally similar molecules in the body, the target substance is expected to behave in a substantially similar manner to the source substance. The target substance is therefore predicted LD50 >2000 mg/kg bw in the OECD 402 study when conducted in the rat. By extension, the target substance is considered not to fulfil the criteria for acute toxicity under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

4. DATA MATRIX
See appended full justification document.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

4-phenylbenzophenone

EC Number:

218-345-2

EC Name:

4-phenylbenzophenone

Cas Number:

2128-93-0

Molecular formula:

C19H14O

IUPAC Name:

{[1,1'-biphenyl]-4-yl}(phenyl)methanone

Test material form:

solid

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)

Test animals

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.

Administration / exposure

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

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.