Chloroform

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study investigated potential adverse effects of long-term chloroform exposure by comparing workers frequently exposed to chloroform vapours to those not known to be exposed to occupational hazards. Both groups were examined clinically and for neurobehavioural performance. The group sizes were sufficient to guarantee a reliable statistical comparison of the exposure and control groups.

Data source

Reference

Reference Type:

publication

Title:

Studies on the toxicity and maximum allowable concentration of chloroform

Author:

Li LH, Jiang XZ, Liang YX, Chen ZQ, Zhou YF, Wang YL

Year:

1993

Bibliographic source:

Biomedical and Environmental Sciences 6, 179-186

Materials and methods

Study type:

health record from industry

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chloroform

EC Number:

200-663-8

EC Name:

Chloroform

Cas Number:

67-66-3

Molecular formula:

CHCl3

IUPAC Name:

trichloromethane

Details on test material:

not applicable

Method

Type of population:

occupational

Ethical approval:

no

Details on study design:

In order to find possible exposure-effect relationship and the toxicity of chloroform after long-term exposure at low concentration, an extensive medical examination and neurobehavioral testing was conducted in 61 workers frequently exposed to chloroform at their workplaces and 83 control workers. The clinical examination was carried out by two clinical physicians. Serum enzymatic activities of asperate aminotransferase (ALT), gamaglutamyltransferase (r-GT) and adenosine deaminase (ADA) together with serum levels of prealbumin (PA) and transferrin (Tf) were analysed. Serum blood urea nitrogen (BUN) was chosen to reflect the kidney functions. WHO recommended Neurobehavioral Core Test Battery was used to test the neurobehavioral function following the principles listed in Operation guide (WHO 1986).

Results and discussion

Results:

The concentrations of chloroform vapour in the air of working places ranged from 4.27 to 141.25 mg/m3 with a geometric mean of 20.46 mg/m3. Workers in exposure group 1 had an average exposure level of 13.49 mg/m3, and workers in exposure group 2 of 29.51 mg/m3. All workers had experienced exposure to chloroform for 1 to 15 years. The common symptoms in exposed group 1 were dizziness, fatigue, somnolence, insomnia, increase of dreams, hypomnesia, anorexia and palpitation and their incidence was significantly increased compared with the control. The hepatomegaly rate had no signficant difference with that of control 1. The findings on liver and kidney functions are shown in Table 2. Exposure group 1 was different from Control 1 in transferrin, whereas exposure group 2 was different from Control 1 in prealbumin and transferrin. Table 3 shows the Profile of Mood State of the workers examined in the study. Scores of passive mood states categorised as depression, anger and fatigue were obviously higher in exposed workers than those of Control 2. The results of the neurobehavioural test are given in Table 4. It could be shown that occupational exposure to approximately 30 ppm chloroform negatively influenced the outcomes of some of the neurobehavioral tests.

Any other information on results incl. tables

Table 1: Characterisation of the subjects

	Exposure group (n = 61)	Control 1 (n = 23)	Control 2 (n = 60)
Age (years, mean ± SD)	36 ± 5	36.8 ± 3.9	36 ± 6.2
Male (Number, %)	26 (42.6)	9 (39.1)	26 (43.3)
Female (Number, %)	35 (57.4)	14 (60.9)	34 (56.7)
Smoking (Number, %)	21 (34.4)	8 (34.7)	21 (35)
Non-smoking (Number, %)	40 (65.6)	15 (65.3)	39 (65)

Table 2: Comparison of rates of abnormal serum enzymatic activities and BUN levels

Indicators	Control 1 (n = 23)		Exposure group 1 (n = 23)
	Number	%	Number	%
ALT	0	0	0	0
ADA	0	0	0	0
r-GT	2	8.7	2	0.3
PA	3	13.0	23	37.7*
Tf	10	43.5	47	77.0*
BUN	0	0	0	0

* X-square test with Control 1, p < 0.01

Table 3: Scores of Profile of Moods State in Exposed workers and Control 2 workers

Mood	Control 2 (n = 60)	Exposure group (n = 60)
	mean ± SD	mean ± SD
Tension	8.85 ± 3.34	8.73 ± 3.52
Depression	9.17 ± 2.18	10.92 ± 4.55*
Anger	9.95 ± 3.68	14.07 ± 3.34**
Vigor	15.43 ± 4.15	17.12 ± 6.34
Fatigue	7.52 ± 4.91	13.70 ± 4.59*
Confusion	6.12 ± 3.54	6.22 ± 2.65

Table 4: Results of neurobehavioural test

Testing	Control 2 (n = 60)	Exposure group 1 (n = 14)	Exposure group 2 (n = 46)
	mean ± SD	mean ± SD	mean ± SD
SVRT	0.26 ± 0.03	0.27 ± 0.05	0.32 ± 0.14**
SDS	56.18 ± 8.49	56.85 ± 12.53	51.70 ± 12.11*
SAD	39.45 ± 4.47	41.07 ± 4.97	40.54 ± 4.47
DS	15.78 ± 2.51	17.93 ± 2.92	15.63 ± 3.17**
BVR	8.92 ± 1.10	8.00 ± 1.80	7.07 ± 1.53**
PtA	245.98 ± 42.99	198.50 ± 37.88**	195.00 ± 50.98**

* X-square test with control 1, p < 0.05; ** X-squre test with control 1, p < 0.01; SVRT: simple virtual reaction time; SDS: symbol-digit substitution; SAD: Santa Ana manual dexterity; DS: digit span; BVR: Benten visual retention; PtA: pursuit aiming

Applicant's summary and conclusion

Conclusions:

Exposure to chloroform vapours at concentrations ranging from 5 to 140 mg/m3 at the working place adversely affected the health of workers in comparison with unexposed workers. It was demonstrated, that the negative health effect is concentration-dependent. It was concluded that a workplace concentration of 20 mg chloroform/m3 was sufficient to protect the health of workers.

Executive summary:

In a workers health survey potential adverse health effects of occupational long-term exposure to chloroform vapours was investigated by comparing the serum enzymatic activities, serum blood urea nitrogen levels, and neurobehavioural performance of two groups of exposed workers to groups of unexposed control workers. Measurements by gas chromatography of vapour concentrations of chloroform at different working places had shown concentrations ranging from 5 to 140 mg/m3, and two groups of exposed workers were differentiated: one group experienced mean exposures of 13.5 mg/m3, whereas the other experience mean exposures of 29.5 mg/m3. It was demonstrated that the group of workers exposed to the higher chloroform levels was statistically significantly different from unexposed controls in many of the health endpoints, while the group of workers exposed to the lower chloroform concentration level was similar to unexposed controls in most of the health endpoints investigated in the study. From this it was concluded that an occupational threshold concentration of 20 mg chloroform/m3 was sufficient to protect the health of workers.