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Toxicological information

Health surveillance data

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Administrative data

Endpoint:
health surveillance data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Correlation between DMAC exposure and hepatotoxic effects are not clear (exposure related to biological exposure index of 30 mg NMAC/g creatinine but urine sampling only during the second half of monitoring period; no data about inhalation exposure concentration or dermal exposure; low number of urine samples).

Data source

Reference
Reference Type:
publication
Title:
Dimethylacetamide-induced hepatic injuries among spandex fibre workers
Author:
Jung SJ, Lee CY, KIM SAH, Park KS, HA BG, KIM J, YU JY, Choi T
Year:
2007
Bibliographic source:
Clin Toxicol (Phila) 45(5):435-439

Materials and methods

Study type:
health record from industry
Endpoint addressed:
repeated dose toxicity: inhalation
repeated dose toxicity: dermal
Principles of method if other than guideline:
Hepatoxicity in workers related to DMAC exposure in two spandex factories (Gumi Industrial Zone, Korea) was studied.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
No details available.

Method

Type of population:
occupational
Ethical approval:
not applicable
Details on study design:
Authors monitored 1045 workers exposed to DMAC from January 2001 to July 2004 in 2 plants producing polyurethane elastic fibres and using DMAC as solvent. A pre-placement health examination, post-placement health examinations every 10 days for the next three months, and semi-annual periodic health examinations thereafter were performed; pre-placement health examination included hepatic function tests, AST, ALT, and y-glutamyl transpeptidase (GGT) and tests for viral hepatitis; urine NMAC (N-methylacetamide, marker for DMAC exposure, as described in the section 'Basic toxicokinetics' of this report) and the above three hepatic enzymes were tested at the semi-annual periodic health examinations. Urine sampling was conducted only during the period 2003-2004. 228 urinary NMAC results were collected from the department with hepatic injuries related to DMAC exposure (1056 samples from other department, presumably not exposed, no details given); urine sampling after shift.

Results and discussion

Results:
There were 38 workers with DMAC-induced hepatic injury (DIHI) according to DIHI diagnosis criteria. Three of the 38 cases of DIHI were re-exposed to DMAC, and hepatic injury re-occurred. The latent periods of 29 DIHI cases were within 2 months of their first exposure to DMAC; no cases showed a latent period longer than 6 months.
The median of urinary NMAC results of DIHI group (228 samples from the department of 21 DIHI cases) was 25.1 mg/g creatinine (range: 4.6-196.5 mg/g). This was higher than that of other urinary NMAC results, 11.8 mg/g creatinine (range: 0.1-133.9 mg/g).

Any other information on results incl. tables

Elimination of workplace exposure to DMAC resulted in a decline of elevated ALT levels.

Applicant's summary and conclusion

Conclusions:
There were some indications for DMAC-induced hepatic injuries in 38 out of 1045 monitored workers but no sufficient quantitative data on exposure.
Executive summary:

In the study, 1045 workers exposed to DMAC from January 2001 to July 2004 in 2 plants producing polyurethane elastic fibres and using DMAC as solvent are described. A pre-placement health examination, post-placement health examinations every 10 days for the next three months, and semi-annual periodic health examinations thereafter were performed; pre-placement health examination included hepatic function tests, AST, ALT, and y-glutamyl transpeptidase (GGT) and tests for viral hepatitis; urine NMAC (N-methylacetamide, marker for DMAC exposure) were tested at the semi-annual periodic health examinations. Urine sampling was conducted only during the period 2003-2004. 228 urinary NMAC results were collected from the department with hepatic injuries related to DMAC exposure (1056 samples from other department, presumably not exposed, no details given); urine sampling after shift.

The study meets scientific standards but correlation between DMAC exposure and hepatotoxic effects was not clear (exposure was related to the biological exposure index of 30 mg NMAC/g creatinine but urine sampling was conducted only during the second half of the monitoring period; there were no data about inhalation exposure concentration or dermal exposure; low number of urine samples).

Data on biological exposure index are not suitable for quantitative estimation of DMAC exposure (samples related to the corresponding department of the plant but not to the DIHI cases; urine samples were only available during the second half of the monitoring period; no clear difference between control and DIHI values).

There were some indications for DMAC-induced hepatic injuries in 38 out of 1045 monitored workers but no sufficient quantitative data on exposure.