Benzoic acid, C12-15-alkyl esters

Endpoint summary

Description of key information

Acute toxicity oral: The acute oral lethal dose (LD50) of the test material in Wistar rats was calculated as being 34500 mg/kg bodyweight. In a second study the acute oral lethal dose (LD50) of the test material in Wistar -derived albino rats was > 5 g/kg bodyweight. 
Acute toxicity dermal: The acute dermal lethal dose (LD50) of the test material in albino rabbits was found to be greater than 2000 mg/kg bodyweight.
Acute toxicity inhalation: In the Acute Inhalation Toxicity study on Wistar-derived rats the LC50 of the test material was determined as being > 200 mg/l. There was a 10 % mortality observed in the exposed rats. Under the conditions if this study the test material is considered to be not toxic by inhalation to rats.

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:

14. Dec. 1978 - 06. Feb. 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

other: equivalent to standard acute tox method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

female, body weight at study start: 178 - 240 g
male, body weight at study start: 174 - 252 g
standard laboratory conditions
acclimatisation perid: 7 days
fasted overnight prior to administration of the test material
food and water ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 40 mL/KG

Doses:

range finding: 0.5, 1, 3, 5, 10, 25, 40 g/KG
main study: 30, 33, 37, 40 g/KG

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation after 1, 3, 6, 24 hours on the 1st day and daily thereafter; weighing at study start ans study end
- Necropsy of survivors performed: yes
- Other examinations performed: body weight and clinical signs

Statistics:

LD50 calculated according to Litchfield and Wilcoxin

Sex:

male/female

Dose descriptor:

LD50

Effect level:

34 500 mg/kg bw

Based on:

test mat.

Mortality:

Mortality started with second dose (33 g/KG).

Clinical signs:

other: Hair matted and unkempt Complete hair loss, scabs Crust-like substance covering entire skin surface Pyloric and intestinal mucosa reddened

Gross pathology:

Hair matted and unkempt
Complete hair loss, scabs
Crust-like substance covering entire skin surface
Pyloric and intestinal mucosa reddened

 

Dosage (g/KG)	Sex	# dead /# dosed	%
30	3 M : 3 F	0/3 : 0/3	0
33	3 M : 3 F	2/3 : 2/3	67
37	3 M : 3 F	3/3 : 2/3	83
40	3 M : 3 F	1/3 : 3/3	67

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral lethal dose (LD50) of the test material in Wistar rats was calculated as being 34500 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Wistar rat. Four groups of three fasted males and females were treated with the test material at dose levels of 30000, 33000, 37000 and 40000 mg/kg bodyweight. The test material was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. Mortality: Mortality started with second dose (33 g/KG). Clinical Observations: Hair matted and unkempt Complete hair loss, scabs Crust-like substance covering entire skin surface Pyloric and intestinal mucosa reddened Bodyweight: Body weight loss starting with the second dose (33 g/KG) Necropsy:  Pyloric and intestinal mucosa reddened Conclusion: The acute oral lethal dose (LD50) of the test material in Wistar rats was calculated as being 34500 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

34 500 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16. Feb. 1979 - 27. Apr. 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

other: trade name

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey
- Weight at study initiation: 200 -246 g
- Diet: Wayne animal feed, ad libitum
- Water: ad libitum
- Acclimation: animals were conditioned prior to use

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: plastic chamber
- Exposure chamber volume: three-cubic-foot
- Source and rate of air: preconditioned supportive air at 5 L/minute
- System of generating particulates/aerosols: Preconditioned supportive air was supplied and the test material was presented from a compressor activated generator or timer operated solenoid to continue a nominal chamber concentration of 200 mg / liter air

TEST ATMOSPHERE
- nominal concentration of 200 mg / liter air

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): 200 mg / liter air

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

200 mg / liter air

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily (1, 3, 6, 24 hours after exposure on day 1) and weighing at start and end of the experiment
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight , necropsy

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 200 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

Dose Level (mg/l) Sex # dead /# dosed Mortality ( %)
200 5 M : 5 F 1/5 : 0/5 10

Clinical signs:

other: Slight depression observed 1 hour after exposure at all 10 animals, otherwise no abnormal clinical signs within 14 days after exposure.

Body weight:

Body weight gain at 9 survived animals 14 days after exposure.
Body weight loss at 1 animal that died on 9th day after exposure.

Gross pathology:

Animal #1: All lobes of right lung enlarges and consolidated. Animal died on day 9.
Animals #2 - #10: No gross changes observed.

 

Dose (mg/l

Animal No. and Sex

Body weight (g)

Hours:   1    3    6   24

Days:   2   3    4   5   6   7 --14

Body weight (g)

200

1 M

202

SD

N

N

N

N

N

N

N

N

N+  -

156

200

2 M

230

SD

N

N

N

N

N

N

N

N

N    N

296

200

3 M

232

SD

N

N

N

N

N

N

N

N

N    N

324

200

4 M

230

SD

N

N

N

N

N

N

N

N

N    N

290

200

5 M

246

SD

N

N

N

N

N

N

N

N

N    N

312

200

6 F

204

SD

N

N

N

N

N

N

N

N

N    N

222

200

7 F

200

SD

N

N

N

N

N

N

N

N

N    N

226

200

8 F

200

SD

N

N

N

N

N

N

N

N

N    N

262

200

9 F

200

SD

N

N

N

N

N

N

N

N

N    N

210

200

10 F

200

SD

N

N

N

N

N

N

N

N

N    N

220

 

N  = Normal

SD = Slight Depression

+ = Animal Death 

Animal No. 1: All lobes of right lung enlarges and consolidated; died on day 9.

Animal No. 2-10: No gross changes observed.

Interpretation of results:

GHS criteria not met

Conclusions:

In the Acute Inhalation Toxicity study on Wistar-derived rats the LC50 of the test material was determined as being > 200 mg/l.
There was a 10% mortality observed in the exposed rats. Under the conditions if this study the test material is considered to be not toxic by inhalation to rats.

Executive summary:

In an Acute Inhalation Toxicity study ten albino rats (5M:5F, 200 -246 g body weight) were exposed to concentrations of 200 mg test material / liter air for 1 hour and observed for two weeks. Mortality, clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.  

Mortality: 10 % (1/10 animals)

Clinical Observations: Slight depression was observed at all animals 1 h after exposure; otherwise no abnormal clinical signs within 14 days observation period.

Body weight: Body weight gain at 9 animals after the 14 days observation period, body weight loss at 1 animal that died after exposure.

Necropsy: No gross changes observed at 9 animals. In the one dead animal all lobes of right lung enlarges and consolidated.

Conclusion: The LC50 of the test material was determined as being > 200 mg/l. Under the conditions if this study the test material is considered to be not toxic by inhalation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

200 mg/m³ air

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:

14. Dec. 1978 - 06. Feb. 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

other: equivalent to standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

female, body weight at study start: 1.5 - 1.66 kg
male, body weight at study start: 1.51 - 1.87 kg
standard laboratory conditions
food and water ad libitum

Type of coverage:

other: trunk of each animal encased in a sleeve of plasticised material

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The animals were prepared by clipping the skin of the trunk free of hair. One-half of the animals were further prepared by introducing epidermal abrasions over the clipped skin surface, thus enhancing penetrability of the test material throug the stratum corneum.
Following the exposure period the sleeve was removed and the skin sites gently cleansed.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation after 1, 3, 6, 24 hours on the 1st day and daily thereafter; weighing at study start and study end
- Other examinations performed: body weight and clinical signs

Statistics:

Limit test

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One dead animal was observed.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

not performed

 

Dosage (mg/KG)	Sex	# dead /# dosed	%
2000	3 M : 3 F	1/3 : 0/3	17

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal lethal dose (LD50) of the test material in albino rabbits was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 2001/59/EC.for classification and labelling of dangerous substances and preparations.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in albino rabbits. A group of six animals (3 males and 3 females) was given a single, 24-hour dermal application of undiluted test material to intact and abraded skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. Mortality: There was one dead animal. Clinical Observations: There were no signs of systemic toxicity. Dermal Irritation: There were no signs of dermal irritation. Bodyweight: 3 animals showed expected gains in bodyweight and the other 3 animals showed body weight loss over the study period. Conclusion: The acute dermal lethal dose (LD50) of the test material in albino rabbits was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

An acute oral toxicity study was performed in Wistar-derived albino rats similar to OECD TG 401. A group of ten (5 males, 5 females) rats was treated with the test material at a dose level of 5.0 g/kg bodyweight. The test material (used as received) was single dosed orally. Clinical signs and bodyweight development were monitored for 14 days post-dosage. All animals were subjected to gross necropsy.

Mortality: No mortality was observed.

Clinical signs: Normal, no changes were observed.

Bodyweight: Body weight gain was observed in all treated animals.

Necropsy: Indication of enlarged spleen noted in 9 of 10 animals.

Conclusion: The acute oral lethal dose (LD50) of the test material in Wistar-derived albino rats was > 5 g/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

 

A second acute oral toxicity study similar to OECD TG 401 is available. The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Wistar rat.

Four groups of three fasted males and females were treated with the test material at dose levels of 30000, 33000, 37000 and 40000 mg/kg bodyweight. The test material was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality: Mortality started with second dose (33 g/KG).

Clinical Observations: Hair matted and unkempt Complete hair loss, scabs Crust-like substance covering entire skin surface Pyloric and intestinal mucosa reddened

Bodyweight: Body weight loss starting with the second dose (33 g/KG)

Necropsy:  Pyloric and intestinal mucosa reddened

Conclusion: The acute oral lethal dose (LD50) of the test material in Wistar rats was calculated as being 34500 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

 

Supporting data on the source substance Benzoic acid isononylester:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following: OECD 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001).

A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test material was administered orally undiluted. 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 Bodyweight: All animals showed expected gains in bodyweight over the study period.

Necropsy: No abnormalities were noted at necropsy

Conclusion: The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated from the flow chart given in the respective OECD guideline as being greater than 2500 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC.

 

Acute inhalation toxicity

In an acute Inhalation Toxicity study similar to OECD TG 403 ten albino rats (5M:5F, 200 -246 g body weight) were exposed to concentrations of 200 mg test material / liter air for 1 hour and observed for two weeks. Mortality, clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.  

Mortality: 10 % (1/10 animals)

Clinical Observations: Slight depression was observed at all animals 1 h after exposure; otherwise no abnormal clinical signs within 14 days observation period.

Body weight: Body weight gain at 9 animals after the 14 days observation period, body weight loss at 1 animal that died after exposure.

Necropsy: No gross changes observed at 9 animals. In the one dead animal all lobes of right lung enlarges and consolidated.

Conclusion: The LC50 of the test material was determined as being > 200 mg/l. Under the conditions if this study the test material is considered to be not toxic by inhalation.

Supporting data on the source substance Benzoic acid isononylester:

A study was performed to assess the acute inhalation toxicity of the test material according to OECD 403 "Acute Inhalation Toxicity" referenced as Method B2 in Commission Directive 92/69/EEC "Acute Toxieity - Inhalation" (which constitutes Annex V of Couneil Directive 67/548/EEC).

A group of ten Sprague-Dawley Crl:CD® (SD) IGS BR strain rats (five males and five females) was exposed to an aerosol atmosphere. The animals were exposed far four hours using a no se only exposure system, followed by a fourteen day observation period. No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.22 mg/L. It was therefore considered that the acute inhalation median lethal concentration (LC50) of Benzoic acid isononylester, in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat, was greater than 5.22 mg/L.

 

Acute dermal toxicity

An acute dermal toxicity study similar to OECD TG 402 was performed in albino rabbits.

A group of six animals (3 males and 3 females) was given a single, 24-hour dermal application of undiluted test material to intact and abraded skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study.

Mortality: There was one dead animal.

Clinical Observations: There were no signs of systemic toxicity.

Dermal Irritation: There were no signs of dermal irritation.

Bodyweight: 3 animals showed expected gains in bodyweight and the other 3 animals showed body weight loss over the study period.

Conclusion: The acute dermal lethal dose (LD50) of the test material in albino rabbits was found to be greater than 2000 mg/kg bodyweight.

 

Supporting data on the source substance Benzoic acid isononylester:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat according to OECD 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Commission Directive 92/69/EEC Method B3 Acute Toxicity (Dermal).

A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of undiluted test material 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: There were no signs of dermal irritation.

Bodyweight: All animals showed expected gains in bodyweight over the study period.

Necropsy: No abnormalities were noted at necropsy.

Conclusion: The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

 

 

There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

Based on the available data, the substance does not require classification for acute toxicity according to regulation (EC) 1272/2008.