Benzoic acid, 2-([1,1'-biphenyl]-4-ylcarbonyl)-

Endpoint summary

Description of key information

Based on the results of the acute studies, the test substance is considered to be of low acute toxicity via oral and dermal routes

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:

From February 06, 2014 to May 15, 2014

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)

Deviations:

yes

Remarks:

see 'Any other information on materials and methods'

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

see 'Any other information on materials and methods'

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

Batch No.: 5307; Purity: 99.9%

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Harlan Laboratories UK, Ltd, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 161 - 180 g
- Fasting period before study: overnight
- Housing: in groups in suspended solid floor polypropylene cages furnished with wood flakes
- Diet: ad libitum (2014C Teklad Global Rodent)
- Water: ad libitum
- Acclimatation period: at least 5 d
ENVIRONMENTAL CONDITIONS

- Temperature: 19-25°C
- Humidity: 30-70%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE

- Concentration in vehicle: 30 - 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: the substance was not soluble in water or arachis oil BP

- Preparation: the test substance was formulated within two hours of beeing applied to the test system. It is auumed that the formulation was stable for this duration
- Rationale for the selection of the starting dose: In absence of data regarding the toxicity of the test substance, 300 mg/kg was chosen as the starting dose
- Analysis: No analysis was conducted to determine homogeneity, concentration or stability of the test substance formulation

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: after 1/2 h, 1 h, 2 h and 4 h after adminstration and once daily afterwards
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - recorded prior to dosing and seven ad fourteen days after treatment

A group of three fasted females was treated with the test substance at a dose level of 300 mg/kg bw. Based on the results from this dose level, further groups of fasted females were treated at dose level of 2000 mg/kg bw. Dosing was performed sequntially. The test substance was administrated orally as a solution in dimethyl sulphxide. All animals were dosed once only by gavage, using a metal canulla attached to a graduated syringe. Clinical signs and body weight development were monitored during the study. All animals were subject of the gross necropsy.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Hunched posture observed in all animals treated at 300 mg/kg bw and three animals treated at 2000 mg/kg bw. Ataxia and/or pilo-erection were also noted at 2000 mg/kg bw. There were no signs of systemic toxicity noted in three animals treated at a dose lev

Gross pathology:

No abnormalities were noted.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the study conditions, the LD50 of the test substance in female Wistar rats was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance PBBA to Wistar rats according to OECD Guideline 423 and EU Method B.1, in compliance with GLP. A group of three fasted females was treated with the test substance at a dose level of 300 mg/kg bw. Based on the results from this dose level, further groups of fasted females were treated at a dose level of 2000 mg/kg bw. Dosing was performed sequentially. The test substance was administered orally as a solution in dimethyl sulphoxide. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There was no mortality. There were no signs of systemic toxicity at any of the doses. No abnormalities were noted at necropsy. Under the study conditions, the LD50 of the test substance in female Wistar rats was determined to be >2000 mg/kg bw (Pooles, 2014).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline compliant study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

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:

From February 06, 2014 to May 15, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Batch No.: 5307; Purity: 99.9%; Appearane: white powder

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Wistar (RccHanÔ:WIST) rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-h exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Type of coverage:

semiocclusive

Vehicle:

DMSO

Details on dermal exposure:

For the purpose of the study the test substance was weighed according to each animal’s individual body weight and moistened with dimethyl sulphoxide prior to application.
The extent of absorption of the test substance was not determined.

On the day before treatment the back and flanks of each animal were clipped free of hair. Using available information on the toxicity of the test substance, a group of five male and five female rats was treated with the test substance at a dose level of 2000 mg/kg. The appropriate amount of the test substance, moistened with dimethyl sulphoxide, was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with dimethyl sulphoxide followed by distilled water to remove any residual test substance. The animals were returned to group housing for the remainder of the study period.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five male and five female

Control animals:

not required

Details on study design:

The animals were observed for deaths for overt signs of toxicity at 30 min, 1, 2 and 4 h after dosing and subsequently once daily for fourteen days. After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the scale explained in the section for additional information. Any other skin reactions, if present were also recorded. Individual body weights were recorded prior to application of the test substance on Day 0, 7 and 14. At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Light brown discoloration of the epidermis was noted at the test sites of three males one and two days after dosing. Reduced regrowth of fur was also noted at the test sites of two of these animals during the study. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Conclusions:

Under the study conditions, the LD50 of the test substance in Wistar rats was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance PBBA to Wistar rats according to OECD Guideline 402 and EU Method B.3, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 h, semi-occluded dermal application of the test substance to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths or signs of systemic toxicity. Light brown discoloration of the epidermis was noted at the test sites of three males one and two days after dosing. There were no signs of dermal irritation recorded at the test sites of the remaining animals. No abnormalities were seen at necropsy. Under the study conditions, the LD50 of the test substance in Wistar rats was determined to be >2000 mg/kg bw (Pooles, 2014).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline compliant study

Additional information

Oral:

A study was conducted to determine the acute oral toxicity of the test substance PBBA to Wistar rats according to OECD Guideline 423 and EU Method B.1, in compliance with GLP. A group of three fasted females was treated with the test substance at a dose level of 300 mg/kg bw. Based on the results from this dose level, further groups of fasted females were treated at a dose level of 2000 mg/kg bw. Dosing was performed sequentially. The test substance was administered orally as a solution in dimethyl sulphoxide. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There was no mortality. There were no signs of systemic toxicity at any of the doses. No abnormalities were noted at necropsy. Under the study conditions, the LD50 of the test substance in female Wistar rats was determined to be >2000 mg/kg bw (Pooles, 2014).

 

Inhalation:

Given the intermediate use of the test substance as a monomer, there is an inhalation exposure potential to the workers to an extent, during its transfer process into the reactors. However, as discussed in the toxicokinetic section, the absorption potential following inhalation exposure is expected to be similar to the oral route, due to the ionic nature and dissociation potential of the test substance. Therefore, testing via inhalation route will less likely result in any additional hazard identification and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation. The risk assessment due to the acute inhalation exposure potential in workers is considered to be covered by the implementation of the long-term inhalation DNEL and the contained working conditions as risk management measures.

 

Dermal:

A study was conducted to determine the acute dermal toxicity of the test substance PBBA to Wistar rats according to OECD Guideline 402 and EU Method B.3, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 h, semi-occluded dermal application of the test substance to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths or signs of systemic toxicity. Light brown discoloration of the epidermis was noted at the test sites of three males one and two days after dosing. There were no signs of dermal irritation recorded at the test sites of the remaining animals. No abnormalities were seen at necropsy. Under the study conditions, the LD50 of the test substance in Wistar rats was determined to be >2000 mg/kg bw (Pooles, 2014).

Justification for classification or non-classification

Based on the results of the acute oral and dermal toxicity studies, the test substance is not considered to require classification for acute effects according to EU CLP (EC 1272/2008) criteria.