Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
44.37 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
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:
25.17 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
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

A DNEL was only determined for worker exposure in an industrial setting, since Caffeine is produced in a closed system and for general population exposure is regulated by the pharmaceutical law, the European cosmetic legislation and the European Food Safety Authorisation (EFSA).

Short-term systemic and local effects / long-term exposure and local effects:

Acute/short-term DNELs were not calculated as they are covered by calculation of long-term DNELs.

No local dermal effects or skin and eye irritation/corrosion as well as no respiratory irritation were observed. No sensitizing activity was detected.

Therefore the following DNEL(s) for local effects and short term exposure were not determined:

- Dermal DNEL for acute / short-term exposure - systemic effects

- Inhalation DNEL for acute / short-term exposure - systemic effects

- Dermal DNEL for acute / short-term exposure - local effects

- Inhalation DNEL for acute / short-term exposure - local effects

- Dermal DNEL for long-term exposure - local effects

- Inhalation DNEL for long-term exposure - local effects

Long-term exposure - systemic effects

Based on the No-(Adverse)-Effect-Level for oral repeated-dose toxicity of Caffeine (CAS No. 58-08-2)the endpoint-specific Derived-No-Effect-Level (DNEL) was calculated. For Caffeine, following subchronic exposure in a drinking water study (NTP 1983) a NOAEL of 151 mg/kg body weight/day was determined. Using an over all assessment factor, including the assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 3 for worker according to ECETOC 2003, exposure duration of 2 (sub-chronic to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for oral exposure was calculated as follows: 151 mg/kg/day/ (4*3*2*1*1*1) = 6.292 mg/kg body weight /day.

 

- Dermal DNEL for long-term exposure - systemic effects

For the determination of the dermal DNEL, the NOAEL of 151 mg/kg bw/day of the same rat oral subchronic repeated dose study (NTP 1983) was used.

The dermal absorption was assumed as 25 % according to van de Sandt et al., 2004 (Reg Tox and Pharma 39, 271 -281. Accordingly, for dermal exposure the corrected starting point was calculated as 604 mg/kg body weight/day. Using the overall assessment factor of 24, including assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 3 for worker according to ECETOC 2003, exposure duration of 2 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for dermal exposure was calculated as follows: 604 mg/kg/day/ (4*3*6*1*1*1) = 25.167 mg/kg body weight /day.

 

- Inhalation DNEL for long-term exposure - systemic effects

Using the same rat oral subchronic repeated dose study (NTP 1983), the calculation of the endpoint specific DNEL for inhalation repeated-dose toxicity for workers was performed. The conversion of the rat oralNOAEL of 151 mg/kg bw/day to a corrected inhalatoryhuman NOAEL was based on the different respiratory volume of the rat (0.38 m³/kg/day and the different rate during light activity at work (10 m³) and standard conditions (6.7 m³).

CorrectedNOAEL= 151 mg / m³ * 1/0.38 m³/kg/day * 6.7 m³ (8h) / 10 m³ (8h) = 266.2 mg/m³.Using the overall assessment factor of 18, including assessment factors for intraspecies extrapolation of 3 for worker according to ECETOC 2003, exposure duration of 2 (sub-chronic to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for inhalative exposure was calculated as follows: 266.2mg/m³/ (3*2*1*1*1) = 44.373mg/m³.

 

 

 

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

For general population no DNEL was calculated, since Caffeine is produced in a closed system and for general population exposure is regulated by the pharmaceutical law (tablets), the European cosmetic legislation (cosmetics) and the European Food Safety Authorisation (EFSA) (drinks).