Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Result and method described in suffiscient detail. Peer-reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Absorption of cumene through the respiratory tract and excretion of dimethylphenylcarbinol in urin
Author:
Senczuk W, Litewka B
Year:
1976
Bibliographic source:
British Journal of Industrial Medicine 33, 100-105

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
basic toxicokinetics
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
10 healthy volunteers were exposed heads only to defined concentrations of cumene. Absorption of cumene as well as excretion of metabolite 2-phenylpropan-2-ol (=dimethylphenylcarbinol) was measured
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
general
Subjects:
- Number of subjects exposed:
- Sex: 5 male, 5 female
- Age: 20-35 years old
- Race: not specified
- Demographic information: Investigations are assumed to be performed in Poland
- Known diseases: healthy according to medical examination
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
Each person was exposed to three exposure concentrations at an interval of 10 day
Concentrations tested: 240, 480, and 720 mg/m3
Exposure duration: 8h, divided in two 2.5h and one 2h exposure, with a 30 min break after the exposures
Examinations:
1) Retention of cumene: concentration in inhaled air - concentration in exhaled air
2) Dimethylphenylcarbinol in urine, time of collection of urine: 2.5, 5.5, 8, 10, 12, 14, 24, 32, 40 and 48 h after start of exposure

Results and discussion

Clinical signs:
None
Results of examinations:
Retention of cumene in lungs: 64 % at 0.5 h of exposure, 45 % at the end of the exposure to vapours at 240, 480 and 720 mg/m3;
Excretion of 2-phenylpropan-2-ol in the urine: maximum was observed after 6 to 8 h of exposure, approaching zero after 48 h;
average percentage yield of the conversion of cumene into 2-phenylpropan-2-ol was 35 %.

Any other information on results incl. tables

Cumene absorbed during 8 h exposure

Sex

Cumene in chamber [mg/m3]

Mean absorbed cumene [mg]

Range
[mg]

Women

240

270.8

202.0-386.0

480

526.0

404.0-772.0

720

789.0

606.0-1158.0

Men

240

466.4

327.0-730.0

480

934.0

654.0-1460.0

720

1400.0

981.0-2190.0

Excretion of demethylphenylcarbinol

Sex

Cumene in chamber

Mean excretion [mg]

Range
[mg]

Women

100

96.6

73-130.6

300

219

151.6-343.6

600

325

201.4-447

Men

100

2.9

1.3-5.3

300

5.3

2.7-9.6

600

7.4

2.2-16.0

Applicant's summary and conclusion

Executive summary:

Absorption, metabolism and excretion 10 healthy volunteers (5 men and 5 women) aged between 20 and 35 years were exposed with their heads to 240, 480 and 720 mg cumene/m3 for 8 h periods. Retention of cumene vapours in lungs during exposure decreased from 64 % at 0.5 h of exposure to 45 % at the end of the exposure. Excretion of 2-phenylpropan-2-ol in the urine at different time intervals (2.5 to 48 h after the beginning of exposure) was correlated linearly to the amount of absorbed cumene; excretion time course: a maximum was observed after 6 to 8 h of exposure, excretion decreased after cessation of exposure approaching zero after 48 h; average percentage yield of the conversion of cumene into 2-phenylpropan-2-ol was 35 %.