Glycerides, C16-18 and C18-unsatd., deodorizer distillates

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:

3 854 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

24

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

'Glycerides C16-18 and C18-unsatd., deodoriser distillates' is used in a variety of industrial settings for a number of applications including as a source material for energy production and as a raw material or feedstock for production of other substances and preparations.

The main type of exposure at the workplace will be via the dermal route. Given the fact thatglycerides C16-18 and C18-unsatd., deodorizer distillatesdoes not volatilize and is not handled in powder or aerosol form, respiratory exposure is not relevant.

Given the above facts, and as recommended in Chapter R.8 of the REACH Technical Guidance Documents, long-term DNELs were derived for workers potentially exposed through the dermal route only.

As specified in Section 1.2, the composition of this substance varies depending on the vegetable oil feedstock type and the process efficiency of the deodorizer. It is composed of0 - 80 % glycerides and15 - 95 %fatty acids (including their esters), 0-40 % unsaponifiable matter, e.g. tocopherols, sterols, sterol esters and hydrocarbons, e.g. squalene.Several DNELs were therefore calculated, based on glycerides / fatty acid data (to cover compositions with high amounts of these constituents and low unsaponifiable matter) as well as unsaponifiable matter data (to cover compositions with high unsaponifiable matter).

DNEL long-term, workers, dermal based on glycerides data

Glycerides of chain lengths ranging from C16-18, including C18-unsatd. show a comparable toxicity profile, with low acute and repeated-dose toxicity to animals and humans. They are not mutagenic, not carcinogenic and do not induce reproductive toxicity. Overall, the most appropriateNOAEL identified from a subchronic (90 day) repeated dose oral toxicity study in the rat was equivalent to 19 % in diet, i.e. ca. 9,250 mg/kg bw/day fed as soybean oil. This value was used as a starting point for deriving a DNEL_{long-term, dermal}.

In a first step, the starting point oral value should be corrected for route-to-route extrapolation. In accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’), in the absence of data, no default factor (i.e. factor of 1) should be introduced for oral-to-dermal extrapolation, basedon the assumption that dermal absorption will in general not be higher than oral absorption. However, for highly lipophilic substances (log Kow > 4), according to Section R.7.12.2.1 of REACH guidance document R7.C (May 2008), a 10% default dermal absorption percentage value is recommended (in the absence of test data) for the purpose of risk assessment.The next steps consist in applying assessment factors (AF) for interspecies difference, intraspecies variation, exposure duration, dose-response and quality of the database, as presented in Section R.8.4.3 of REACH guidance document R.8 and the ECE TOC Technical Report 110, 2010 . The overall AF in this case corresponds to 24 (see Table).

The resulting DNEL_{long-term, workers, dermal}is equivalent to 3,854 mg /kg bw/day.

Table. Derivation of DNEL_{long-term, workers, dermal}for 'glycerides C16-18 and C18-unsatd., deodorizer distillates' based onglycerides of chain lengths C16 – 18 including C18 unsatd. as represented by soybean oil.

	Value	Comment
Starting point	9,250 mg/kg bw/day	Oral NOAEL fromrepeated dose toxicity test in rat
Starting point corrected for route to route extrapolation factor (oral-to-dermal extrapolation)	92,500 mg/kg bw/day	Correction for difference in absorption between routes
Assessment factor	4	Interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
	3	Combined inter and intraspecies difference - remaining non-metabolic differences (workers)
	2	Exposure duration (subchronic study)
	1	Dose-response (starting point is a NOAEL)
	1	Quality of whole database
DNELlong-term,workers, dermal	3,854 mg/kg bw/day	-

DNEL long-term, workers, dermal based on unsaponifiable matter data

The unsaponifiable matter of 'glycerides C16-18 and C18-unsatd., deodorizer distillates' is composed of various types of substances, including tocopherols, sterols, sterol esters and hydrocarbons such as squalene. Information presented in Section 5.1 suggests that tocopherols are the most likely to penetrate across skin and are therefore the most relevant substances on which to base a dermal risk assessment. It should be noted that the following calculations are extremely conservative, as they assume 100% tocopherol content in unsaponifiable matter, whereas the actual value is much lower (e.g. max. 10 - 20%). They also assume a substance containing 100% unsaponifiable matter, whereas the maximum amount is 40%.

The toxicology of tocopherols has been reviewed and different authors have derived acceptable daily intakes (ADI). JECFA for example published in 1987 an ADI of 0.15 - 2.0 mg/kg bw. This value is proposed as a starting point for calculating a DNEL_{long-term, dermal}. based on unsaponifiable matter data.

In accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’), in the absence of data, no default factor (i.e. factor of 1) should be introduced for oral-to-dermal extrapolation, basedon the assumption that dermal absorption will in general not be higher than oral absorption.However, for highly lipophilic substances (log Kow > 4), according to Section R.7.12.2.1 of REACH guidance document R7.C (May 2008), a 10% default dermal absorption percentage value is recommended (in the absence of test data) for the purpose of risk assessment. The estimated Kow value for tocopherols is 11.1-12.2. The next steps consist in applying assessment factors (AF) for interspecies difference, intraspecies variation, exposure duration, dose-response and quality of the database, as presented in Section R.8.4.3 of REACH guidance document R.8 and the ECETOC Technical Report 110, 2010. The overall AF in this case corresponds to 6 (see Table).

The resulting DNEL_{long-term, workers, dermal}is equivalent to 0.25 mg /kg bw/day.

Table.Derivation of DNEL_{long-term, workers, dermal}for 'glycerides C16-18 and C18-unsatd., deodorizer distillates' based onunsaponifiable matter (tocopherols)

	Value	Comment
Starting point	0.15 mg/kg bw/day	Oral NOAEL fromrepeated dose toxicity test in rat
Starting point corrected for route to route extrapolation factor (oral-to-dermal extrapolation)	1.5 mg/kg bw/day	Correction for difference in absorption between routes
Assessment factor	1	Interspecies difference - allometric (metabolic rate) scaling (human-to-human)
	3	Combined inter and intraspecies difference - remaining non-metabolic differences (workers)
	1	Exposure duration (ADI)
	1	Dose-response (starting point is an ADI)
	2	Quality of whole database
DNELlong-term,workers, dermal	0.25 mg/kg bw/day	-

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:

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

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

No consumer exposure.