3-chloropropene

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: - no guideline followed - overview article only

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Study type:

case control study (retrospective)

Endpoint addressed:

neurotoxicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Retrospective epidemiologic study after several cases of polyneuropathy were observed among workers.
- 26 workers of factory A and 27 workers of factory B
- a questionaire about occupational history, symptoms, past illness, and family history.
- Physical and neurological examinations (including ENMG), visual acuity and visual field detection, skin temperature measurement and rheography
- determination of clinical chemical, hematologic and urinalysis parameters

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropene

EC Number:

203-457-6

EC Name:

3-chloropropene

Cas Number:

107-05-1

Molecular formula:

C3H5Cl

IUPAC Name:

3-chloroprop-1-ene

Details on test material:

no data, workers were exposed to 3-chloropropene, sodium sulphite and allyl sulphonate in unknown purities

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study):
confirmation of neurotoxicity of 3-chloropropene

METHOD OF DATA COLLECTION
- Type: Questionnaire, Work history, Clinical tests and Exposure concentration measurement
- Details: All subjects were given detailed questionaires about occupational history, symptoms, past illness, and family history. Physical and neurological examinations, visual acuity and visual field detection, skin temperature measurement, rheography of extremities, and electrocardiography were done.
Electroneuromyography (ENMG) was carried out with a DISA 1500 type EMG system recording muscle potentials from hands and legs and measuring motor conduction velocities of median, ulnar and lateral popliteal nerves, and sensory conduction velocities of median, ulnar and sural nerves, and sensory conduction velocities of median, ulnar and sural nerves.
Laboratory tests included routine blood and urine tests, liver function (serum glutamic pyruvic transaminase, thymol turbidity and thymol flocculation test), blood glucose, electrolytes, nonprotein nitrogen, erythrocyte sedimentation rate and PSP test.
Electroencephalogram, basal metabolic rate, blood lactic dehydrogenase, serum and urine protein electrophoresis were also done in some of the
subjects.

STUDY PERIOD:
Epidemiological surveys, clinical observations and follow-up studies on the 3-chloropropene exposed workers and intoxicated patients in two factories manufacturing sodium allyl sulphonate were done within 1973-1982.

SETTING:


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): all workers of the factories
- Selection criteria: no selection described, probably all workers included
- Total number of subjects participating in study: 53
- Sex/age/race: factory A: female, 20 - 51 yrs, chinese; factory B: 14 male/13 female, 18 - 41 yrs, chinese
- Smoker/nonsmoker: not reported
- Total number of subjects at end of study: 53
- Matching criteria: no matching criteria defined, all exposed worker were analyzed
controls are mentioned in a table on nerve conduction velocity but no details were reported concerning this control group (46 - 50 persons)



COMPARISON POPULATION
- no details reported


HEALTH EFFECTS STUDIED
- see above under METHOD OF DATA COLLECTION

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE:
inhalation of vapours

TYPE OF EXPOSURE MEASUREMENT: not decribed in detail, very likely area air sampling


EXPOSURE LEVELS:
factory A: 2.6 - 6'6650 mg/m³ (= 0.84 - 2'145 ppm, calculated with 1 ppm = 3.1 mg/m³)
factory B: 0.2 - 25.13 mg/m³ (= 0.065 - 8.1 ppm)


EXPOSURE PERIOD:
factory A: 2.5 mo - 6 yrs
factory B: 1 - 4.5 yrs


POSTEXPOSURE PERIOD: not clearly reported


DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: not specified

Statistical methods:

not reported

Results and discussion

Results:

Factory A:
- Observations :
Initial complaints of lacrymation and sneezing in all workers gradually diminishing. Most workers developed numbness, tingling, cramping pains and weakness in the distal part of the extremities. Shortest latent period 2 months.
2/3rds of thegroup showed symmetrical distal sensory deficits and there was decreased muscular strength in 57% of these. Ankle reflexes reduced in 42.3%. No muscular atrophy. EMG abnormalities of the type described above were observed in 10/19 subjects examined. Insomnia, dizziness
and anorexia were rare.
No other changes attributable to 3-chloropropene exposure were found on physical, haematological or routine clinical chemical examination. The affected workers were diagnosed as exhibiting toxic polyneuropathy due to allyl chloride overexposure.
- Treatment:
Workers were removed from exposure to allyl chloride and treated with Vitamins B1, B6, B12, ATP, Securine and traditional Chinese medicines. Some patients took acupuncture and physiotherapy. After 2-4 months treatment, the majority of patients showed steady improvement of symptoms, but in severe cases ankle reflex loss and EMG abnormalities remained for years.
Factory B:
- Observations: Symptoms were similar to those described above for Factory A, but milder and without eye and upper respiratory tract irritation.
The cramping pain was reduced and few abnormal neurological signs were found. EMG investigation revealed an increase in polyphasic potentials and increased duration of motor unit potentials without any denervation potentials in 13/27 workers examined. The degree of peripheral neuropathy was
much less in this group of workers.
No other changes attributable to 3-chloropropene exposure were found on physical, haematological or routine clinical chemical examination.
- Treatment:
Same as for workers of Factory A

Confounding factors:
Not clearly discussed but declared that "Possible etiological factors of neuropathy except exposure to allyl chloride were excluded".

Confounding factors:

not reported

Strengths and weaknesses:

exposure levels not clearly definable, confounding factors not clearly discussed though noted that they have been excluded

Any other information on results incl. tables

- Table 1: General aspects of the two exposed groups

groups	No. of subjects	age	sex		Exposure level of 3-chloropropene (mg/m3)	exposure duration
			M	F
Factory A	26	20-51	0	26	2.6 - 6650	2.5 m - 6 y
Factory B	27	18- 41	14	13	0 - 25.13	1 y - 4.5 y

- Table 2: Symptons and signs

symptoms and signs	Factory A (26 subjects)		Factory B (27 subjects)
	No.	%		No.
Symptoms
weakness of extremities	24	92.3	18	66.7
cramping pain	17	65.3	5	18.5
tingling sensation	15	57.6	9	33.3
numbness in hands and feet	10	38.5	11	40.7
coldness in hands and feet	8	30.7	8	29.6
dizziness	6	23.1	10	37.0
insomnia	7	26.9	5	18.5
anorexia	5	19.2	1	3.7
Signs
Distal sensory impairment pain            pain	17	65.3	4	14.8
light touch	16	61.5	0	0
vibration sensation	16	61.5	1	3.7
position sensation	6	23.1	0	0
decreased muscular strength	15	57.6	0	0
diminished ankle reflexes	11	42.3	2	7.4
tenderness       in calf muscles	5	19.2	2	7.4
enlarged liver	2	7.6	0	0

- Table 3: Electromyographic changes

Groups	Factory A (19 subjects)		Factory B (27subjects)
	hands	legs	hands	legs
No. of muscles sampled	20	34	39	27
Insertional activity            normal	20	34	39	27
prolonged	0	0	0	0
Spontaneous potentials            fibrillation	3	5	0	0
positive sharp waves	0	3	0	0
Motor unit potentials            duration normal	20	34	12	25
prolonged	0	0	27	2
polyphasic potentials            normal	18	30	17	25
increased	2	4	22	2
Recruitment of motor units            interference pattern	3	4	35	26
reduced interference pattern	16	23	4	1
discrete pattern	1	7	0	0

- Table 4: Comparison of nerve conduction between the control group and two exposed groups

nerves examined	MCV Mean ± SD (m/s)					distal     latency Mean ± SD (m/s)
	control	Factory A	p	Factory B		control	Factory A	p	Factory B	p
Median nerve
No. examined	46	5		27		46	5		27
elbow - wrist	60.28 ±	57.36 ±		56.3 ±
	5.27	4.19	> 0.05	7.3	<0.05
wrist - APB						3.63 ±	5.16 ±		3.96 t
						0.56	0.22	<0.01	0.67	<0.05
Lat. Popliteal N.
No. examined	50	9		26		50	9		26
popliteal-ankle	55.68 ±	46.24 ±		51.09 ±
	5.32	1.67	<0.001	6.65	<0.01
ankle - EDB						4.53 ±	6.38 ±		4.35 ±
						0.7	0.37	<0.01	1.28	>0.05

MCV----motor conduction velocity;

APB----musculus abductor pollicis brevis;

EDB----musculus extensor digitorum brevis.

Applicant's summary and conclusion

Executive summary:

In the present study (He 1985) an epidemionlogical study was conducted on chinese workers of two different factories exposed to vapours of 3 -chloropropene at levels of 2.6 - 6'6650 mg/m³ (= 0.84 - 2'145 ppm, factory A, 1970 - 1977) and 0.2 - 25.13 mg/m³ (= 0.065 - 8.1 ppm, factory B, 1978 - 1982) for 2.5 mo - 6 yrs (factory A) and 1 - 4.5 yrs (factory B). The groups consisted of 26 female workers, 20 - 51 yrs of age for factory A and 14 male and 13 female workers, 18 - 41 yrs of age for factory B. The study was conducted from 1973 to 1982.

All subjects were given detailed questionaires about occupational history, symptoms, past illness, and family history. Physical and neurological examinations, visual acuity and visual field detection, skin temperature measurement, rheography of extremities, and electrocardiography were done.

Electroneuromyography (ENMG) was carried out with a DISA 1500 type EMG system recording muscle potentials from hands and legs and measuring motor conduction velocities of median, ulnar and lateral popliteal nerves, and sensory conduction velocities of median, ulnar and sural nerves, and sensory conduction velocities of median, ulnar and sural nerves.

Laboratory tests included routine blood and urine tests, liver function (serum glutamic pyruvic transaminase, thymol turbidity and thymol flocculation test), blood glucose, electrolytes, nonprotein nitrogen, erythrocyte sedimentation rate and PSP test. Electroencephalogram, basal metabolic rate, blood lactic dehydrogenase, serum and urine protein electrophoresis were also done in some of the subjects.

For the group of workers the following observations were made:

Initial complaints of lacrymation and sneezing in all workers gradually diminishing. Most workers developed numbness, tingling, cramping pains and weakness in the distal part of the extremities. Shortest latent period 2 months.

2/3rds of the group showed symmetrical distal sensory deficits and there was decreased muscular strength in 57% of these. Ankle reflexes reduced in 42.3%. No muscular atrophy. EMG abnormalities of the type described above were observed in 10/19 subjects examined. Insomnia, dizziness and anorexia were rare.

No other changes attributable to 3-chloropropene exposure were found on physical, haematological or routine clinical chemical examination. The affected workers were diagnosed as exhibiting toxic polyneuropathy due to allyl chloride overexposure.

In the group of workers from factory B which were generally lower exposed the following observations were made:

Symptoms were similar to those described above for Factory A, but milder and without eye and upper respiratory tract irritation.

The cramping pain was reduced and few abnormal neurological signs were found. EMG investigation revealed an increase in polyphasic potentials and increased duration of motor unit potentials without any denervation potentials in 13/27 workers examined. The degree of peripheral neuropathy was much less in this group of workers.

No other changes attributable to 3-chloropropene exposure were found on physical, haematological or routine clinical chemical examination.

Confounding factors:

Not clearly discussed but declared that "Possible etiological factors of neuropathy except exposure to allyl chloride were excluded".

As treatment workers were removed from exposure to allyl chloride and treated with Vitamins B1, B6, B12, ATP, Securine and traditional Chinese medicines. Some patients took acupuncture and physiotherapy. After 2-4 months treatment, the majority of patients showed steady improvement of symptoms, but in severe cases ankle reflex loss and EMG abnormalities remained for years.

The incidence of polyneuropathy in workers exposed to 3 -chloropropene vapours was found to be dose related.

The symptoms were persistent, some lasting for years in severe cases.