Benzoic acid, 4-[(1-oxodecyl)oxy]-

Endpoint summary

Description of key information

Acute oral toxicity:
The test item did not cause any mortality or clinical signs or necropsy findings after single oral gavage administration to female rats at 2000 mg/kg bw in a GLP compliant guideline study. The LD50 (female rat) was greater than 2000 mg/kg body weight.
Acute dermal toxicity:
The test item did not cause any mortality or clinical signs or necropsy findings after single dermal administration to male and female rats at 2000 mg/kg bw in a GLP compliant guideline study. The LD50 (male/female rat) was greater than 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed GLP and OECD guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Gartenstrasse 27, D-33178 Borchen
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: mean = 178.8 g
- Fasting before study: yes
- Housing: in transparent macrolon® cages (type IV) on soft wood granulate* in an air-conditioned room, 3 animals per cage
- Diet (e.g. ad libitum): ssnif® R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: Sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 % suspension
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: stability and homogeneity

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to toxicity data of related compounds

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: no symptoms

Gross pathology:

no macroscopically visible changes

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute oral toxicity testing of the test item in the female rat yielded a median lethal dose (LD50) above 2000 mg/kg body weight.

Executive summary:

The test item was tested for acute oral toxicity in femal rats according to OECD guideline 423 (limit test).

After administration of 2000 mg/kg body weight neither deaths nor symptoms occurred.

One female animal showed a small loss of body weight at the end of the study. In the other animals development of body weight was not impaired.

All animals were killed at the end of the observation period. They showed no macroscopically visible changes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restrictions - well performed GLP and OECD guideline study

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

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

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Wistar (RccHan:WIST) strain 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 acclimatisation 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 Hour 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 analysed 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. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. 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:

The appropriate amount of test item, moistened with dimethyl sulphoxide (DMSO), was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area).

Duration of exposure:

24 hours (residual test item was removed with cotton wool moistened with dimethyl sulphoxide followed by distilled water)

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 male
5 female

Control animals:

not required

Details on study design:

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 item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.
The appropriate amount of test item, 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 item. The animals were returned to group housing for the remainder of the study period.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours 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 following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema Formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.
Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 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.

Statistics:

No statistical analysis was performed.

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: There were no signs of systemic toxicity.

Gross pathology:

A cavity in the right kidney was noted at necropsy of one male and was considered to be a genetic defect and not test item related. No abnormalities were noted at necropsy of the remaining animals that were killed at the end of the study.

Other findings:

Dermal Reactions

Very slight erythema was noted at the test site of three females (2-0, 2-3, 2-4) which was reversible within 3,8 and 9 days. Small superficial scattered scabs were noted at the test site of two females (2-0, 2-4) from day 6 to day 10 or 14. Hardened light brown coloured scab and scab lifting at the edges to reveal dried blood were also noted at the test site of one female (2-0). All signs of irritation were fully reversible within the observation period with the exception of one female (2-0).
No signs of dermal irritation were noted at the test site of the remaining animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction. The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Method. A group of ten animals (five males and five females) was given a single, 24 hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. Very slight erythema was noted at the test site of three females. In two of these females scabbing and scab lifting at the edges to reveal dried blood was noted at Day 6 and all subsequent observations. All signs of irritation were fully reversible within the observation period with the exception of one female. No signs of dermal irritation were noted at the test site of the remaining animals. 

Bodyweight. Animals showed expected gains in bodyweight over the study period except for one female which showed expected gain in bodyweight during the first week but bodyweight loss during the second week.

Necropsy. A cavity in the right kidney was noted at necropsy of one male and was considered to be a genetic defect and not test item related. No abnormalities were noted at necropsy of the remaining animals that were killed at the end of the study.

Conclusion. The acute dermal median lethal dose (LD₅₀) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restrictions - well performed GLP and OECD guideline study

Additional information

Justification for selection of acute toxicity – oral endpoint
only one study available

Justification for selection of acute toxicity – dermal endpoint
only one study available

Justification for classification or non-classification

LD50 values after acute dermal and oral application were greater than 2000 mg/kg bw.. Since these findings do not meet the criteria for classification as acutely toxic according to the rules laid down in Directive 67/548/EEC and in Regulation (EC) No 1272/2008, classification is not warrantable.