Mesitylene

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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline human experimental study, published in peer reviewed literature, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Biological monitoring for trimethylbenzene exposure: A human volunteer study and a practical example in the workplace

Author:

Jones K, Meldrum M, Baird E, Cottrell S, Kaur P, Plant N, Dyne D and Cocker J

Year:

2006

Bibliographic source:

Ann. Occup. Hyg., 6, 593-598

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Inhalation study in human volunteers. 3,5-dimethyl benzoic acid (DMBA) and its glycine conjugate were determined in urine; blood and exhaled air were analysed for 1,3,5-TMB.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3,5-trimethylbenzene

IUPAC Name:

1,3,5-trimethylbenzene

Constituent 2

Reference substance name:

Mesitylene

EC Number:

203-604-4

EC Name:

Mesitylene

Cas Number:

108-67-8

Molecular formula:

C9H12

IUPAC Name:

mesitylene

Details on test material:

- Name of test material (as cited in study report): 1,3,5-trimethylbenzene
- Analytical purity: >98%
- Supplier: Aldrich Chemical Company Ltd, Dorset, England

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 4
- Sex: 2 male, 2 female
- No further details reported

Ethical approval:

confirmed, but no further information available

Route of exposure:

inhalation

Reason of exposure:

intentional

Exposure assessment:

not specified

Details on exposure:

Exposures were performed in a room of approx.8 m3 volume built for this purpose. The methodology has been described in Brooke I, Cocker J, Delic JI et al (1998). Dermal uptake of solvents from the vapour phase: an experimental study in humans. Ann Occup Hyg; 42: 531-40.

Examinations:

- Urine analysis: Individual pre-exposure urine samples obtained. All urine was collected (in timed samples) for 1 week and analysed for the metabolites of 1,3,5-TMB i.e. 3,5-DMBA and/or its glycine conjugate. (3,5-dimethylhippuric acid). Creatine concentration was measured.
- Haematology: Venous blood samples were taken prior to, and at 1 hr intervals from, the start of exposure until 1 hr post-exposure.
- Lung function parameters: Prior to entering the chamber, and at timed intervals during (hourly) and after (0.03, 03, 1, 1.5, 5.5 and 18 h) exposure, breath samples were collected and the exhaled solvent vapours analysed by GC-MS. Blood and breath samples were analysed for TMB.
- Other: Before and during exposure, volunteers completed a detailed questionnaire for recording subjective experiences of sensory irritation of the eyes, nose and throat.

Results and discussion

Clinical signs:

Exposure was well tolerated, with very little sensory irritation reported by all the volunteers. The odour of the solvent was noted, but awareness of it reduced as the exposure time progressed.

Results of examinations:

- Urine analysis: Peak excretion of urinary 3,5-DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol/mol creatinine. The majority of the absorbed dose was excreted within 50 hr after exposure but levels of 3,5-DMBA were still detectable after 160 hr. Elimination of 3,5-DMBA in urine was biphasic with half-lives of 13 and 60 hr.
- Haematology: 1,3,5-TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 µmol/L during exposure. There was little decline 1 hour post-exposure.
- Lung function parameters: Breath 1,3,5-TMB levels peaked within an hour of exposure commencing and averaged 137 nmol/L during exposure. Elimination of 1,3,5-TMB in breath was biphasic with an initial half-life of 60 min and a final half life of 600min.
- The percentage retention of the inhaled dose was estimated to be 52-56% for males and 23-39% for females.

Applicant's summary and conclusion

Executive summary:

Peak excretion of urinary 3,5-DMBA occurred 4-8 hr after the end of exposure and averaged 40 mmol/mol creatinine. The majority of the absorbed dose was excreted within 50 hr after exposure but levels of 3,5-DMBA were still detectable after 160 hr. Elimination of 3,5-DMBA in urine was biphasic with half-lives of 13 and 60 hr. 1,3,5-TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 µmol/L during exposure. There was little decline 1 hour post-exposure. Breath 1,3,5-TMB levels peaked within an hour of exposure commencing and averaged 137 nmol/L during exposure. Elimination of 1,3,5-TMB in breath was biphasic with an initial half-life of 60 min and a final half life of 600min. The percentage retention of the inhaled dose was estimated to be 52-56% for males and 23-39% for females.