Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

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:
1.6 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

According to the REACH “Guidance on information requirements and chemical safety assessment”, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

 

Vitamin A is a micronutrient essential for most mammalian species. The term “Vitamin A” is used as a generic descriptor for compounds, that exhibit the biological properties of retinol or other closely related naturally occurring derivatives. Vitamin A occurs in nature primarily as retinyl esters (retinyl palmitate, retinyl aceate and retinyl propionate) and retinol. It is an essential factor for the growth and maintenance of higher organisms.

The tolerable upper intake level for preformed vitamin A (Retinol and retinyl esters) is set at 3000 RE/day or approx. 10000 IU/day for adults (Scientific opinion EFSA, 2008). The recommended daily intake of Vitamin A for humans is approximately 0.6–1.0 mg RE/day (2000–3300 IU/day) for men, and 0.5-0.8 mg RE/day (1670–2660 IU/day) for women, depending on their age and reproductive status (WHO, EFSA, IARC). Since either a deficiency in Vitamin A exposure lead to adverse effects such as developmental toxicity, the derivation of a DNEL should take into account such levels. However, the classical approach, i.e. a DNEL derivation from the basis of no adverse effect levels by using standart assessment factors might not be applicable, since conservative use of assessment factors can lead to DNELs below recommended daily intake levels, beeing adverse per se. On the basis of the derived tolerable upper intake level for preformed vitamin A, a internal systemic safe level for retinyl palmitate in workers is set at 0.078 mg/ kg bw/d.

 

1 mg Retinyl palmitate = 550 RE

Derived tolerable upper intake level = 3000 RE/day

Derived tolerable upper intake level - retinyl palmitate = 1x3000/550 = 5.455 mg/day

Systemic safe level - retinyl palmitate = 5.455/70 = 0.078 mg/kg bw/d

 

 

In a weight of evidence from the available data on toxicokinetics, the dermal absorption rate for humans is set at 5% of the applied dose. Considering the comparative assessment of oral versus dermal administration observed by Nohyek et al, 2006, the oral absorption is expected to be extensively higher (up to 15 fold increases), which substantiates the assumption of a 100% oral absorption of retinyl palmitate.

 

For derivation of the long-term systemic dermal DNEL, the internal systemic safe level was converted in line with the procedure for route to route extrapolation, recommended in the current guidance document (R8, ECHA 2008):

 

Long-term systemic dermal DNEL = 0.078 *(100/5)= 1.6 mg/kg bw/d

 

 

No DNELs were derived for local effects after short term or after long term inhalative exposure as the substance exhibits no hazardous potential in terms of these endpoints.

No DNELs were derived for local effects after short term or after long term dermal exposure since the respective systemic long term DNEL is considered sufficient to ensure the absence of local effects.

No DNELs were derived for systemic effects after short term dermal exposure, since the respective systemic long term DNEL is considered sufficient to ensure the absence of acute toxic effects.

No DNELs were derived for systemic effects after short term or after long term inhalative exposure, since inhalation is not considered a relevant route of exposure due to physical chemical properties of retinyl palmitate (liquid with a lack of relevant vapour pressure) and the absence of relevant exposure scenarios including formation of respirable aerosols.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Since all relevant uses are outside the scope of REACH, i.e. use in food or feeding stuff or medicinal products as referred to in Article 2 (5a,b) of 1907/2006/EEC or use in cosmetic products as defined in Directive 76/768/EEC, no DNELS have been derived for the general population according to "Guidance on information requirements and chemical safety assessment (Chapter R8).