Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
95.89 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.89 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The toxicity of Tri-C18-22 (even numbered)-alkyl 2-hydroxypropane-1,2,3-tricarboxylate was not specifically determined. But the structural related substance Tri (hexyl, octyl, decyl) citrate with shorter chain esters was investigated. The most appropriate endpoint for derivation of a DNEL is the rat oral NOAEL of > 1000 mg/kg bw/d taken from a well conducted subacute toxicity study of the structural related substance Tri (hexyl, octyl, decyl) citrate. Based on the acute toxicity data, DNELs do not need to be derived for local or systemic effects for the worker population since the material has a low potential for acute toxicity.

Worker long term exposure - systemic effects (dermal and inhalation) DNELs were calculated from the NOAEL, assuming a 100% dermal absorption rate (worst case). The value was divided by an adjustment factor of 72 (exposure duration factor of 6, interspecies factor of 4, and intraspecies (worker population) factor of 3), leading to a DNEL of > 13.89 mg/kg/d.

The corrected worker inhalation starting point was the corrected NOAEC of 1726 mg/m³ and was derived from the oral NOAEL of 1000 mg/kg/d by multiplying by the inverse of the standard respiratory volume of the rat during an 8 hour period (2.63) and multiplied by the ratio of standard respiratory volume for humans to the 8 hour worker standard respiratory volume (0.67). The corrected starting point was adjusted by a factor of 18 (intraspecies factor (worker) of 3, and exposure duration of 6), resulting in a calculated DNEL of > 95.89 mg/m³.

ASSESSMENT FACTORS:

The Assesment Factors are used according to Ecetoc Technical Report No 86 (ECETOC 2003).

Interspecies Assessment factors:

In addition to the allometric scaling factor of 4 a further interspecies assessment factor of 2.5 (remaining difference) is proposed in REACH Guidance R8, section R8.4.3.3, Table R.8-6, however no scientific basis for this is reported. In Ecetoc Technical Report No 86 (ECETOC 2003), a conclusion was reached that in the absence of a substance specific mode of action, allometric scaling based on metabolic rate is considered to provide an appropriate default assessment factor. As a specific mode of action has not been identified for Tri-C18-22 (even numbered)-alkyl 2-hydroxypropane-1,2,3-tricarboxylate it has not been considered necessary to apply this factor.

Intraspecies assessment factors: A factor for workers of 5 and for the general population of 10 has been suggested by the REACH guidance (8.4.3.1), however, based on several analyses of large data sets and in accordance with many workplace OEL setting practices an intraspecies factor for workers of 3 is considered appropriate for the worker population (ECETOC, 2003). Additionally following a review of human data which included both sexes and a variety of disease states and ages, the use of the 95th percentile is considered sufficiently conservative to account for intraspecies variability in the general population and thus a default assessment factor of 5 is recommended (ECETOC, 2003). ECETOC, 2003, Technical Report No. 86, derivation of Assessment Factors for Human Health Risk Assessment.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The toxicity of Tri-C18-22 (even numbered)-alkyl 2-hydroxypropane-1,2,3-tricarboxylate was not specifically determined. But the structural related substance Tri (hexyl, octyl, decyl) citrate with shorter chain esters was investigated.

The most appropriate endpoint for derivation of a DNEL is the rat oral NOAEL of > 1000 mg/kg bw/d taken from a well conducted subacute toxicity study. Based on the acute toxicity data, DNELs do not need to be derived for local or systemic effects for the general population since the material has a low potential for acute toxicity.

General population long term exposure - systemic effects (oral, dermal and inhalation) DNELs were calculated from the NOAEL, assuming a 100% dermal absorption rate (worst case). The value was divided by an adjustment factor of 120 (exposure duration factor of 6, interspecies factor of 4, and intraspecies (general population) factor of 5), leading to a DNEL of > 8.33 mg/kg bw/d.

The corrected general population inhalation starting point was the corrected NOAEC of 870 mg/m³ and was derived from the oral NOAEL of 1000 mg/kg/d by multiplying by the inverse of the standard respiratory volume of the rat during a 24 hour period (0.87). The corrected starting point was adjusted by a factor of 30 (intraspecies factor (general population) of 5, and exposure duration of 6, resulting in a calculated DNEL of > 29 mg/m³.

The general population oral starting point is > 1000 mg/kg/d. An adjustment factor of 120 is applied (interspecies factor of 4, intraspecies factor (general population) of 5, and exposure duration of 6), leading to a DNEL of > 8.33 mg/kg bw/day.

ASSESSMENT FACTORS:

The Assesment Factors are used according to Ecetoc Technical Report No 86 (ECETOC 2003).

Interspecies Assessment factors:

In addition to the allometric scaling factor of 4 a further interspecies assessment factor of 2.5 (remaining difference) is proposed in REACH Guidance R8, section R8.4.3.3, Table R.8-6, however no scientific basis for this is reported. In Ecetoc Technical Report No 86 (ECETOC 2003), a conclusion was reached that in the absence of a substance specific mode of action, allometric scaling based on metabolic rate is considered to provide an appropriate default assessment factor. As a specific mode of action has not been identified for Tri-C18-22 (even numbered)-alkyl 2 2-hydroxypropane-1,2,3-tricarboxylate it has not been considered necessary to apply this factor.

Intraspecies assessment factors: A factor for workers of 5 and for the general population of 10 has been suggested by the REACH guidance (8.4.3.1), however, based on several analyses of large data sets and in accordance with many workplace OEL setting practices an intraspecies factor for workers of 3 is considered appropriate for the worker population (ECETOC, 2003). Additionally following a review of human data which included both sexes and a variety of disease states and ages, the use of the 95th percentile is considered sufficiently conservative to account for intraspecies variability in the general population and thus a default assessment factor of 5 is recommended (ECETOC, 2003). ECETOC, 2003, Technical Report No. 86, derivation of Assessment Factors for Human Health Risk Assessment.