Registration Dossier

Administrative data

Description of key information

ORAL
LD50 Combined = 367.7 mg/kg bw
Caffeine is of SLIGHT Toxicity based on the LD50 in males and females.
DERMAL
LD50 Combined > 2000 mg/kg bw (no mortality occurred, limit test)
Caffeine of LOW Toxicity based on an LD50 exceeding 2000 mg/kg bw.
INHALATION
LC50 Combined: ca. 4.94 mg/L
Caffeine is of SLIGHT to LOW toxicity based on the LD50 in males and females.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
367.7 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
4 940 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

ORAL

In an acute oral toxicity study (BASF, 1985), groups of young, fasted, Wistar rats (5/sex) were given a single oral dose of Caffeine (purity not given) in 0.5% aqueous carboxymethylcellulose at doses of 178, 261, or 383 mg/kg bw and observed for 14 days.

  • LD50 Males and Females: 367.7 mg/kg bw

Clinical signs of toxicity were unspecific in nature and occurred at any dose level. Mortality was 8/10 (3/5 males and 5/5 females) at 383 mg/kg bw; deaths were observed within 24 hours after dosing. No deaths occurred at lower doses. Body weight was not affected. Pathology of the decedents revealed unspecific changes (general congestion) while no pathological abnormalities were found in survivors that had been sacrificed at the end of the observation period.

Caffeine is of SLIGHT Toxicity based on the LD50 in males and females.

DERMAL

In an acute dermal toxicity study (BASF 1988), a group of male and female Wistar rats (5/sex) was dermally exposed to anhydrous Caffeine (purity not given) in olive oil at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

  • Dermal LD50 Combined > 2000 mg/kg bw (no mortality occurred, limit test)

No deaths, no clinical signs of toxicity, no local findings, and no pathological changes were observed. Body weight gain was unaffected.

Caffeine of LOW Toxicity based on an LD50 exceeding 2000 mg/kg bw.

INHALATION

In an acute inhalation toxicity study (BASF, 1989), groups of young adult Wistar rats (5/sex) were exposed by inhalation route to an aerosol of anhydrous caffeine (purity 99.5%) for 4 hours to nose/head only at analytical concentrations of 2.48 or 4.94 mg/L. Animals then were observed for 14 days.

  • LC50 Males: ca. 4.94 mg/L
  • LC50 Females: ca. 4.1 mg/L
  • LC50 Combined: ca. 4.94 mg/L

Clinical signs of toxicity were mostly unspecific in nature (changes in respiration frequency, reddish nasal discharge, apathy, decreased pain reflex, attempts to escape, aggressive behaviour, gait/position alterations, and/or impaired general state), occurred at all dose levels, and partially persisted until necropsy. Mortality was 6/10 and 0/10 in the low and high dose group, respectively; late deaths were noted. Body weight gain was transiently retarded in low dose males and high dose males and females. In decedents, the following findings were observed at necropsy in some animals general congestion, bloody ulcers in the glandular stomach, intensified hyperemia in the lungs. No pathologic findings were noted in survivors sacrificed at the end of the observation period.

Caffeine is of SLIGHT to LOW toxicity based on the LC50 in males and females.

Human:

Toxic effects (poisoning, overdosing)

Only rare deaths from overdosage of caffeine have been reported(Gilbert, 1976). It has been estimated that 5 g to 10 g may be fatal in man (total dose, appr. 65 cups of coffee taken at one time) (Krantz and Carr, 1951, Rivenes, 1997). Blood concentrations of 10-30 µg/ml may produce restlessness, excitement, tremor, tinnitus, headache and insomnia, low doses (up to 2 µg/ml in blood) stimulate the central nervous system(Ashton, 1987, Stavric, 1988).Some adverse effects like gastric symptoms, insomnia, seizure, and fever were reported after overdosing (appr. 750 mg in an adult) (Lachance, 1982, Stavric, 1988, FitzSimmons and Kidner, 1997, Daroca et al., 1996).

Justification for classification or non-classification

Based on the oral LD50 in rats, Caffeine has to be classified as “harmful if swallowed” according to the Directive 67/548/EC. According to the GHS criteria, Caffeine has to be classified as follows: Acute Oral Toxicity Cat. 4.

Based on the dermal LD50 of > 2000 mg/kg bw in rats, there is no need for classification according to the Directive 67/548/EC. and according to the GHS criteria.

Based on the inhalation LC50 of approximately 4.94 mg/L, Caffeine has not be classified according to the Directive 67/548/EC and to the GHS criteria.