Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Systemic effects (worker)

Basis for delineation of the DNELs systemic effects (worker):

Long-term exposure:

ORAL APPLICATION:

In an OECD TG 408 study the systemic toxic potential of reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate (EC No. 905-983-8; Adimoll BO) was investigated, when administered orally by gavage to Sprague-Dawley rats for 13 weeks.

Three groups, each comprising ten males and ten females, received Adimoll BO at doses of 100, 300 or 1000 mg/kg bw/day, at a volume dose of 4 mL/kg bw. A similarly constituted control group received the vehicle (Arachis oil BP) at the same dose volume.

During the study, thyroid hormone analyses, detailed physical examination and arena observations, sensory reactivity, grip strength, motor activity, body weight, food consumption, visual water consumption, ophthalmic examination, hematology (peripheral blood), blood chemistry, urinalysis, organ weight, macropathology and histopathology investigations were undertaken.

The no-observed-adverse-effect level (NOAEL) of oral administration of Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate (EC No. 905-983-8; Adimoll BO), to Sprague-Dawley rats for 13 weeks was 1000 mg/kg bw /day (the highest applied dose).

In a OECD TG 421 study the oral administration of Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate (EC No. 905-983-8) to rats by gavage, at dose levels of 250, 500 and 1000 mg/kg bw/day was well tolerated in adult animals, with no evidence of toxicity or effects on reproduction. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) for parental animals, reproductive and developmental endpoints was considered to be 1000 mg/kg bw/day (the highest dosage tested).

Short-term exposure:

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.

Based on these results no systemic DNELs need to be derived, because no hazard was identified. 

 

Local effects (worker)

Basis for delineation of the DNELs local effects (worker):

According to OECD TG 404 and 405 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' was tested for skin irritation and for irritation of the mucous membranes of the eyes. No irritation effects were observed neither to the skin of rabbits nor in the mucous membranes of the eyes.

Furthermore, a modified Local Lymph Node Assay (IMDS) was performed according to OECD TG 429 and 406. The results show that there is no indication for a skin sensitizing effect.

Based on these results no local DNELs need to be derived, because no hazard was identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Systemic effects (general population)

Basis for delineation of the DNELs systemic effects (general population):

Long-term exposure:

ORAL APPLICATION

In an OECD TG 408 study the systemic toxic potential of reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate (EC No. 905-983-8; Adimoll BO) was investigated, when administered orally by gavage to Sprague-Dawley rats for 13 weeks.

Three groups, each comprising ten males and ten females, received Adimoll BO at doses of

100, 300 or 1000 mg/kg bw/day, at a volume dose of 4 mL/kg bw. A similarly constituted

control group received the vehicle (Arachis oil BP) at the same dose volume.

During the study, thyroid hormone analyses, detailed physical examination and arena observations, sensory reactivity, grip strength, motor activity, body weight, food consumption, visual water consumption, ophthalmic examination, hematology (peripheral blood), blood chemistry, urinalysis, organ weight, macropathology and histopathology investigations were undertaken.

The no-observed-adverse-effect level (NOAEL) of oral administration of Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate (EC No. 905-983-8; Adimoll BO), to Sprague-Dawley rats for 13 weeks was 1000 mg/kg bw /day (the highest applied dose).

In a OECD TG 421 study the oral administration of Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate (EC No. 905-983-8) to rats by gavage, at dose levels of 250, 500 and 1000 mg/kg bw/day was well tolerated in adult animals, with no evidence of toxicity or effects on reproduction. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) for parental animals, reproductive and developmental endpoints was considered to be 1000 mg/kg bw/day (the highest dosage tested).

Short-term exposure:

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.

Based on these results no systemic DNELs need to be derived, because no hazard was identified. 

 

Local effects (general population)

Basis for delineation of the DNELs local effects (general population):

According to OECD TG 404 and 405 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' was tested for skin irritation and for irritation of the mucous membranes of the eyes. No irritation effects were observed neither to the skin of rabbits nor in the mucous membranes of the eyes.

Furthermore, a modified Local Lymph Node Assay (IMDS) was performed according to OECD TG 429 and 406. The results show that there is no indication for a skin sensitizing effect.

Based on these results no local DNELs need to be derived, because no hazard was identified.