Fatty acids, tall-oil, C12-15-alkyl esters, sulfated, sodium salts

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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:

DNEL (Derived No Effect Level)

Value:

1.67 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Following Risk Assessment European guideline AF Oral to Drmal = 1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

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

Derivation of Quantitative DNELs

Workers may be exposed through dermal contact with the substances and these could involve acute or repeated dose exposures. Based on the expected handling/use and chemical properties of the FLL Substances, inhalation and oral exposure are not considered likely.

DNEL for Long-Term, Dermal, Systemic Effects

The following two repeated dose toxicity studies in rats have been conducted for two symilar substances with similar results obtained for each sample (refer to Table 2):

• 14-day repeated dose toxicity in the rat by oral route (range finding study): NOAEL≥1000 mg/kg bw/d;
• Combined short-term repeated dose toxicity and screening for reproductive/developmental toxicity in the rat by oral route (54 - 56-d duration): NOAEL≥1000 mg/kg bw/d.

The second study meets the definition of subacute according to Chapter R.8 and also included examination of potential reproductive effects. In addition, it is supported by the shorter-term 14-d study where similar results were obtained. Thus, the NOAEL of 1000 mg/kg bw/d was used as the starting point for the estimation of the DNEL for long-term, dermal, system effects for the FLL Substances as a whole. This was the maximum dosage applied in each test; no effects on mortality, health of the test organisms, or reproductive parameters of the test organisms were observe at any of the doses tested.

The oral NOAEL was converted to the corrected dermal NOAEL as prescribed in ECHA Guidance Chapter R.8 according to Equation 1

Where:

Parameters	Definition	Value	Reference/Rationale
ABSoral-rat	relative oral absorption in the rat	1	For oral-to-dermal extrapolation, Chapter R.8 recommends default factors of 1 based on the assumption that, in general, dermal absorption will not be higher than oral absorption.
ABSderm-human	relative dermal absorption in humans	1

 

As recommended by ECHA (under the assumption of equal absorption in rats and humans), this value was used directly as the “corrected” NOAEL for DNEL development and therefore the corrected dermal NOAEL was 1000 mg/kg bw/d.

To estimate the DNEL_{long-term,dermal}, the following assessment factors (AFs) to account for (i) differences in duration of exposure and (ii) key uncertainties associated with the DNEL development were applied to the corrected dermal NOAEL:

AFs	Value	Rationale
Interspecies	4 (allometric scaling) 2.5 (remaining differences)	For systemic effects, Chapter R.8 recommends a (rat-to-human) allometric scaling factor of 4. For systemic effects, Chapter R.8 recommends a factor of 2.5 to account for “remaining differences”.
Intraspecies	5	Chapter R.8 recommends a factor of 5 for workers given that this subpopulationdoes not cover very young, very old and very ill.
Exposure duration	6	The NOAEL study duration was 8 weeks (between subacute and subchronic according to Chapter R.8). Chapter R.8 recommends a subchronic to chronic AF of 2 and a subacute to chronic AF of 6. Erring on the side of caution, the AF of 6 was selected.
Dose-response	1	A NOAEL was used as the starting point for the DNEL and there were no unusual dose-response issues (as described in Chapter R.8) resulting in a default factor of 1.
Quality of database	2	There was correspondence in results for each of the 4 tests conducted on the similar substance and the NOAELs determined in the studies were limit values (i.e.,no effects at the highest test concentration) providing confidence in this NOAEL as a starting point for the DNEL. However, some adjustment is warranted given that no tests on the substance has been performed
Overall AF	600	Product of individual AFs.

 

Note that while most of the AFs are based on the values prescribed in Chapter R.8, the AF for quality of database was based primarily on professional judgement. Chapter R.8 does not prescribe values for quality of database but recommends that quality of database be considered when deriving the DNELs. Selection of the value of 2 for quality of database was intended to reflect uncertainty in possible responses between dermal and oral exposures. The value of 2 is intermediate between the following two situations described by WHO/IPCS (1994):Minor deficiencies in the data exist with respect to quality, quantity or omission; andData base considered complete for the evaluation of the compound under consideration.

Application of the AFs to the corrected dermal NOAEL resulted in aDNEL_{long-term,dermal}of 1.67 mg/kg-bw/d for worker exposure.

 

DNEL for Acute, Dermal, Systemic Effects         

The following acute (single dose) toxicity study in rats has been conducted on the substance

¡  

Although the purpose of the study was to estimate the LD50 for the Samples, the lack of mortality, or clinical effects at any dose allows for inference of a NOAEL of 2000 mg/kg bw (the maximum dose tested). This value was used as the starting point for the estimation of the DNEL for acute, dermal, system effects for the FLL Substances as a whole. It was considered appropriate when compared with the subacute repeated dose oral NOAEL of 1000 mg/kg bw that has also been determined that applies for mortality, clinical effects and reproductive effects. In general, it is expected that single dose toxicity would occur at a higher concentration than subacute repeated-dose toxicity (assuming equal absorption between the two exposure routes) and the lack of a large difference between the two values suggests that the acute NOAEL is reasonably conservative.

To estimate the DNEL_acute,dermal, the following assessment factors (AFs) to account for key uncertainties associated with the DNEL development were applied to the corrected dermal NOAEL:

AFs	Value	Rationale
Interspecies	4 (allometric scaling) 2.5 (remaining differences)	For systemic effects, Chapter R.8 recommends a (rat-to-human) allometric scaling factor of 4. For systemic effects, Chapter R.8 recommends a factor of 2.5 to account for “remaining differences”.
Intraspecies	5	Chapter R.8 recommends a factor of 5 for workers given that this subpopulationdoes not cover very young, very old and very ill.
Dose-response	1	A NOAEL was used as the starting point for the DNEL and there were no unusual dose-response issues (as described in Chapter R.8) resulting in a default factor of 1.
Quality of database	2	Only one study has been performed on the substance, only for Oral pathway
Overall AF	100	Product of individual AFs.

 

Note that an AF was not applied for duration of exposure because the acute exposure scenario was assumed to consider a single exposure, similar to the acute study.

The AF for quality of database was based primarily on professional judgement. Chapter R.8 does not prescribe values for quality of database but recommends that quality of database be considered when deriving the DNELs. Selection of the value of 2 for quality of database was intended to reflect potential uncertainty in responses among test species under varying dosing conditions. The value of 2 is intermediate between the following two situations described by WHO/IPCS (1994):Minor deficiencies in the data exist with respect to quality, quantity or omission; and data base considered complete for the evaluation of the compound under consideration.

Application of the AFs to the corrected dermal NOAEL resulted in aDNEL_acute,dermalof 20 mg/kg-bw for a single worker exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.83 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1 200

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.67 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Repeated dose Toxicity - Oral

The repeated-dose, oral NOAEL of 1000 mg/kg bw/d was used as starting point for estimation of the DNEL for repeated dose oral toxicity for systemic effects under public exposures. As recommended in ECHA TGD Chapter R.8. (under the assumption of equal absorption in rats and humans), this value was used directly as the “corrected” NOAEL for DNEL development.

To estimate the DNEL_{oral-environment}, the following AFs were applied to account for (i) differences between rats and humans and (ii) key uncertainties associated with the DNEL development:

AFs		Value		Rationale
Interspecies		4 (allometric scaling) 2.5 (remaining differences)		For systemic effects, Chapter R.8 recommends a (rat-to-human) allometric scaling factor of 4. For systemic effects, Chapter R.8 recommends a factor of 2.5 to account for “remaining differences”.
Intraspecies		10		Chapter R.8 recommends a factor of 10 for the general public to account for subpopulations including thevery young, very old and very ill.
Exposure duration		6		The NOAEL study duration was 8 weeks (between subacute and subchronic according to Chapter R.8). Chapter R.8 recommends a subchronic to chronic AF of 2 and a subacute to chronic AF of 6. Erring on the side of caution, the AF of 6 was selected.
Dose-response		1		A NOAEL was used as the starting point for the DNEL and there were no unusual dose-response issues (as described in Chapter R.8) resulting in a default factor of 1.
Quality of database		2		There was correspondence in results for each of the 4 tests conducted and the NOAELs determined in the studies were limit values (i.e.,no effects at the highest test concentration) providing confidence in this NOAEL as a starting point for the DNEL, but the tests have been performed only on symilar substances
Overall AF		1200		Product of individual AFs.

 

The AF for quality of database was based primarily on professional judgement. Given the consistent results obtained from four repeated dose studies of symilar substances, and the toxicity observed for other types of studies (i.e.,acute oral and dermal, as well as irritation/corrosivity, mutagenicity and reproductive toxicity screening), it is expected that the starting-point NOAEL would be conservative (i.e.,protective of possible effects via the oral pathway).

Application of the AFs to the corrected oral NOAEL resulted in aDNEL_{oral-environment}of 0.835 mg/kg-day for human exposure via the environment.