Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate

Endpoint summary

Description of key information

The LD50 (rat. oral) is > 5000 mg/kg bw.
The LC50 (rat) is >5000 mg/m³.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no guideline defined, but available information is sufficient for assessment

Principles of method if other than guideline:

Method according to Kärber G, Naunyn-Schmiedebergs Arch. exper. Pathol. Pharmakol. 162, 480 (1931).
Rats were given different doses by gavage of undiluted 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' and observed for 7 days for clinical signs and mortality.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMAL
- Weight at study initiation: 120-180 g
- Housing: single
- Diet ad libitum
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): >20

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Rats wer given different doses by gavage of undiluted 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' and observed for 7 days for clinical signs and mortality.
Method according to Kärber G, Naunyn-Schmiedebergs Arch. exper. Pathol. Pharmakol. 162, 480 (1931).

Doses:

no details given

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

Rats wer given different doses by gavage of undiluted 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' and observed for 7 days for clinical signs and mortality.
Method according to Kärber G, Naunyn-Schmiedebergs Arch. exper. Pathol. Pharmakol. 162, 480 (1931).

Statistics:

calculation according to Burn JH, Biologische Auswertungsmethoden p. 29, Berlin: Springer 1937

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

10.4 mL/kg bw

Remarks on result:

other: 10400 mg/kg bw

Mortality:

no details given

Clinical signs:

other: somnolenz, staggering gait, diarrhea, poor general condition

Gross pathology:

no data

Interpretation of results:

GHS criteria not met

Executive summary:

10 rats per dose received different doses of undiluted 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' by gavage and were observed for 7 days for mortality and clinical finings. Animals showed staggering gait, somnolenz, suffered from diarrhea and poor general condition. The LD50 is 10.4 ml/kg bw accounting for 10400 mg/kg bw (density = 1).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

10 400 mg/kg bw

Quality of whole database:

The study provides relevant information to evaluate the acute oral toxicity and can be evaluated with Klimisch score 2.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9-12 weeks
- Weight at study initiation: males: 293-322 g, females: 215-230 g
- Housing: singly
- Diet ad libitum except during exposure
- Water (e.g. ad libitum except during exposure)
- Acclimation period: 23 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 46-56
- Air changes (per hr): 13
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

The animals were exposed to the test atmosphere for 4 hours and 5 minutes. The exposure period was extended beyond 4 hours to allow the chamber to reach equilibrium. At the end of the exposure period the generation was terminated and the chamber was operated for a further 15 min with clean air. At the end of this period the animals were removed from the exposure tube. Prior to being returned to their cages excess test substance was removed from the fur of each animal.

Atmosphere generation:
The test atmosphere was generated using a 1/4 inch JCO atomizer.
Chamber concentration measurements
Particel size distribution measurements

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

5.08 mg/L = 5080 mg/m³

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

The animals were exposed to the test atmosphere for 4 hours and 5 minutes. The exposure period was extended beyond 4 hours to allow the chamber to reach equilibrium. At the end of the exposure period the generation was terminated and the chamber was operated for a further 15 min with clean air. at the end of this period the animals were removed from the exposure tube. Prior to being returned to their cages excess test substance was removed from the fur of each animal. The animals were observed for 14 days.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 000 mg/m³ air

Exp. duration:

4 h

Remarks on result:

other: all animals survived

Mortality:

No animal died.

Clinical signs:

other: Follwing exposure all animals exhibited irregular respiration but recovered from this sympton by day 3.

Body weight:

All animals lost body weight by day 1 but showed a continued weight gain thereafter through day 14.

Gross pathology:

No gross abnormalities were detected at the end of the 14 day observation period.

Interpretation of results:

GHS criteria not met

Executive summary:

An acute inhalation toxicity test according to OECD TG 403 was conducted to determine the potential of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' to produce toxicity from a 4-hour exposure via inhalation (nose-only exposure) route.

The test atmosphere was generated using a 1/4 inch JCO atomizer. The gravimetric chamber concentration was 5080 mg/m³. The mass median aerodynamic diameter was estimated to be 1.72 µm. All animals survived the exposure to the test atmosphere. Following exposure all animals exhibited irregular respiration. However, the animals recovered from this symptom by day 3 and appeared active and healthy for the remainder of the 14-day observation period. Although all animals lost body weight by day 1, all animals showed a continued weight gain thereafter through day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Thus, the LC50 is > 5000 mg/m³.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 000 mg/m³ air

Quality of whole database:

This GLP study is performed according to Guideline and is evaluated with Klimisch score 1.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

ORAL APPLICATION

10 rats per dose received different doses of undiluted 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' by gavage and were observed for 7 days for mortality and clinical findings. Animals showed staggering gait, somnolenz, suffered from diarrhea and poor general condition. The LD50 is 10.4 ml/kg bw accounting for 10400 mg/kg bw (d = 1).

 

INHALATION EXPOSURE

An acute inhalation toxicity test according to OECD TG 403 was conducted to determine the potential of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' to produce toxicity from a 4-hour exposure via inhalation (nose-only exposure) route.

The test atmosphere was generated using a 1/4 inch JCO atomizer. The gravimetric chamber concentration was 5080 mg/m³. The mass median aerodynamic diameter was estimated to be 1.72 µm. All animals survived the exposure to the test atmosphere. Following exposure all animals exhibited irregular respiration. However, the animals recovered from this symptom by day 3 and appeared active and healthy for the remainder of the 14 -day observation period. Although all animals lost body weight by day 1, all animals showed a continued weight gain thereafter through day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 -day observation period. Thus, the LC50 is > 5000 mg/m³.

 

DERMAL APPLICATION

There is no acute toxicity study with 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'available using the dermal route.

According to Regulation (EC) No. 1907/2006 ANNEX VIII column 2: In addition to the acute toxicity study using the oral route at least the acute toxicity for one other route should be provided. This recommendation is fulfilled because there is another study available with 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' using the inhalation route.

This study is performed according to the respective guideline and is GLP compliant and evaluated with Klimisch score 1. Thus, there is no need to conduct an acute toxicity study with 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' using the dermal route.

Justification for selection of acute toxicity – oral endpoint
The study provides sufficient information to evaluate the acute oral toxicity and can be evaluated with Klimisch score 2.

Justification for selection of acute toxicity – inhalation endpoint
There is only one study available. This GLP study is performed according to Guideline and is evaluated with Klimisch score 1.

Justification for selection of acute toxicity – dermal endpoint
There is no acute toxicity study with 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'available using the dermal route.
According to Regulation (EC) No. 1907/2006 ANNEX VIII column 2: In addition to the acute toxicity study using the oral route at least the acute toxicity for one other route should be provided. This recommendation is fulfilled because there is another study available with 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' using the inhalation route.
This study is performed according to the respective guideline and is GLP compliant and evaluated with Klimisch score 1. Thus, there is no need to conduct an acute toxicity study with 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' using the dermal route.

Justification for classification or non-classification

The LD50 (rat. oral) is > 5000 mg/kg bw.
The LC50 (rat) is >5000 mg/m³.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.