Coffee, bean, roasted, ext.

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

publication

Title:

SIDS Initial Assessment Report for SIAM 14: Caffeine (CAS 58-08-2)

Author:

OECD

Year:

2002

Bibliographic source:

OECD SIDS

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

2 concentrations only

Principles of method if other than guideline:

A third test group (as required by the OECD guideline no. 403) was not included since a third dose level (higher than 4.94 mg/l) was expected to be lethal to all exposed animals.

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Caffeine

EC Number:

200-362-1

EC Name:

Caffeine

Cas Number:

58-08-2

Molecular formula:

C8H10N4O2

IUPAC Name:

1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: caffeine, purity of 99.5 - 100% (dried substance)
- Expiration date of the lot/batch: not available
- Purity test date: not available

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not available
- Stability under test conditions: not available
- Solubility and stability of the test substance in the solvent/vehicle: soluble in water
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not available

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: not available
- Preliminary purification step (if any): not available
- Final dilution of a dissolved solid, stock liquid or gel: not available

OTHER SPECIFICS: none

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: Aerosil R 972 at 2%

Details on inhalation exposure:

The rats were exposed for 4 hours and observed for 14 days (day of exposure = day 0).

Concentrations:

Nominal concentrations of 2.48 and 4.94 mg/l

No. of animals per sex per dose:

5

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 4.94 mg/L air (nominal)

Mortality:

No deaths were observed at the low dose level.
In the high dose group, 6/10 animals died. Late deaths were observed; one male each died at day 0 and 7, respectively; 2, 1, and 1 female died at day 0, 1, and 2, respectively.

Clinical signs:

other: Clinical signs of toxicity included changes in respiration (irregular, accelerated, intermittent, gasping), eyelid closure, salivation, restlessness, attempts to escape, reddish nasal discharge, apathy, and (in the high dose group only) decreased pain ref

Gross pathology:

Pathology revealed general congestion, bloody ulcers in the glandular stomachs, and/or intensified hyperemia in the animals that died. No pathological changes were observed in the survivors.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In an acute inhalation toxicity study in Wistar male and female rats conducted according to OECD test guideline 403, the LC50 value was determined at 4.94 mg/l for caffeine aerosol.

Executive summary:

The acute inhalation toxicity study in Wistar male and female rats conducted according OECD test guideline 403 was performed to assess the acute toxicity potential of caffeine aerosol.

Groups of 5 Wistar rats per sex were exposed to caffeine aerosol at nominal concentrations of 2.48 and 4.94 mg/l using a head-nose inhalation system. The rats were exposed for 4 hours and observed for 14 days. No deaths were observed at the low dose level. In the high dose group, 6/10 animals died. Late deaths were observed; one male each died at day 0 and 7, respectively; 2, 1, and 1 female died at day 0, 1, and 2, respectively.

Clinical signs of toxicity included changes in respiration (irregular, accelerated, intermittent, gasping), eyelid closure, salivation, restlessness, attempts to escape, reddish nasal discharge, apathy, and (in the high dose group only) decreased pain reflex and death. Pathology revealed general congestion, bloody ulcers in the glandular stomachs, and/or intensified hyperemia in the animals that died. No pathological changes were observed in the survivors.

The value of the lethal concentration 50 (LC50) in this study has been determined at 4.94 mg/l, allocaing caffeine in Category 4 based on GHS criteria for acute toxicity classification.