4-chloroaniline

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: IPCS-INCHEM, CICADS 48, 2003

Adequacy of study:

other information

Reliability:

other: IPCS-INCHEM, CICADS 48, 2003

Rationale for reliability incl. deficiencies:

other: no reliability is given as this is a summary entry for IPCS-INCHEM, CICADS 48, 2003

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

4-CHLOROANILINE

Author:

IPCS-INCHEM

Year:

2003

Bibliographic source:

in: Concise International Chemical Assessment Document 48

Reference 2

Reference Type:

publication

Title:

Jahresbericht des Gewerbemedizinalrats für den Aufsichtsbezirk Wiesbaden über das Geschäftsjahr 1922

Author:

Betke [initial not given]

Year:

1926

Bibliographic source:

Veröffentlichungen aus dem Gebiete der Medizinalverwaltung, 578:212¿230

Reference 3

Reference Type:

publication

Title:

Méthhémoglobinémie toxique par des dérivés de l¿aniline: parachloroaniline et paratoluidine

Author:

Faivre M, Armand J, Évreux JC, Duverneuil G, and Colin C

Year:

1971

Bibliographic source:

Archives des Maladies Professionnelles de Medecine du Travail et de Sécurité Sociale, 32:575¿577.

Reference 4

Reference Type:

publication

Title:

Methaemoglobinaemia among neonates in a neonatal intensive care unit

Author:

Hjelt K, Lund J, Scherling B, Bendixen S, Lundstrom S, Stovring S, Voldsgaard P, and Linnet K

Year:

1995

Bibliographic source:

Acta Paediatrica, 84:365¿370

Reference 5

Reference Type:

publication

Title:

Unnamed

Year:

1986

Reference 6

Reference Type:

publication

Title:

Severe methaemoglobinaemia due to para-chloroaniline intoxication in premature neonates

Author:

van der Vorst MMJ, Tamminga P, Wijburg FA, and Schutgens RBH

Year:

1990

Bibliographic source:

European Journal of Pediatrics, 50:72¿73

Reference 7

Reference Type:

publication

Title:

Su di un caso di grave intossicazione acuta da parachloroanilina con intensa metemoglobinemia e con transitorie alterazioni elettrocardiografiche

Author:

Scotti P, and Tomasini M

Year:

1966

Bibliographic source:

Medicina del Lavoro, 51(1):662¿666.

Reference 8

Reference Type:

publication

Title:

Drug-induced methaemoglobinaemia.

Author:

Coleman MD, and Coleman NA

Year:

1996

Bibliographic source:

Drug Safety, 14(6):394¿405.

Reference 9

Reference Type:

review article or handbook

Title:

p-Chloroaniline BUA-Stoffbericht 153

Author:

BUA (Beratergremium umweltrelevanter Altstoffe) (BUA)

Year:

1995

Bibliographic source:

Gesellschaft Deutscher Chemiker (Hrsg Behret), VCH (Verlag Chemie), Weinheim

Materials and methods

Principles of method if other than guideline:

IPCS-INCHEM, CICADS 48, 2003

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-chloroaniline

EC Number:

203-401-0

EC Name:

4-chloroaniline

Cas Number:

106-47-8

Molecular formula:

C6H6ClN

IUPAC Name:

4-chloroaniline

Results and discussion

Any other information on results incl. tables

IPCS-INCHEM, CICADS 48 (2003):

PCA (p-chloroaniline) in humans is a more potent cyanogenic agent than aniline. Dermal absorption plays a predominant role in intoxication (Linch, 1974). Severity of adverse effects may increase with concomitant intake of ethanol (BUA, 1995).

Three cases of severe intoxication have been reported after occupational exposure to PCA (Betke, 1926; Scotti & Tomasini, 1966; Faivre et al., 1971).

One of these cases (Betke, 1926) resulted in death. Severe methaemoglobinaemia was reported in all three cases. The fatal case was accidentally sprayed in the face and on the upper part of his clothing with hot PCA. One of the cases (Faivre et al., 1971) handled powdered PCA. The third case (Scotti & Tomasini, 1966) was likewise exposed to dust while grinding PCA.

An insufficiently documented study reported an inhalation exposure to 44 mg PCA/m3 as being "severely toxic" within 1 min, whereas "signs of illness" appeared after prolonged inhalation of 22 mg/m3 (no further information) (Goldblatt, 1955). In one plant, average workplace air concentrations at two sites in PCA production were 58 mg PCA/m3 (range 37-89 mg/m3) and 63 mg PCA/m3 (range 46-70 mg/m3), respectively. Inhalation and simultaneous dermal absorption resulted in cyanosis, increased methaemoglobin and sulfhaemoglobin levels, the development of anaemia (2 of 6 workers within 4 weeks), and acute intoxication (1/6, who had to discontinue working) (Pacséri et al., 1958). In another plant producing PCA from 4- chloronitrobenzene, 14 workers showed a significant fall in haemoglobin and significant increases in methaemoglobin, which did not correlate with the air concentrations of PCA (values not given in study report) (Monsanto, 1986).

For comparison, in otherwise healthy patients, levels of methaemoglobin in excess of 30% may cause fatigue, headache, dyspnoea, nausea, and tachycardia. Lethargy and stupor, as well as deteriorating consciousness, occur as levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure, and neurological depression. Methaemoglobin levels higher than 70% are usually fatal (Coleman & Coleman, 1996).

Cyanosis and methaemoglobinaemia (14.5-43.5% methaemoglobin; normal range <2.3%) in three premature neonates (gestational age 25-27 weeks) were reported to be associated with PCA contamination of the incubators (no information on PCA concentration) in. Exposure was by percutaneous absorption or by inhalation of PCA-containing vapour produced by the inadvertent use of chlorohexidine gluconate (0.25 g/litre) as a humidifying agent, which decomposed on heating to produce PCA (van der Vorst et al., 1990).

A further report describes the same scenario in a neonatal intensive care unit in, showing that premature neonates developed severe methaemoglobinaemia when exposed to even small amounts of PCA formed from the inadvertent use of a 0.02% chlorohexidine solution as a humidifier in new incubators. The authors estimated that the maximum amount of PCA that the neonate could be exposed to was 0.3 mg/day, provided that all PCA produced was absorbed by the neonate. Thirty-three of 415 neonates (8%) were found to be methaemoglobin positive (mean methaemoglobin concentration 19%; range 6.5-45.5%) during the 8-month screening period. Of those patients with a gestational age of less than 31 weeks, 40% were positive; 15 out of 25 neonates (60%) with a birth weight <1000 g proved to be positive. All the methaemoglobin-positive cases started when the neonate was in the new incubator.

A prospective clinical study showed that immaturity, severe illness, the time exposed to PCA, and low concentrations of NADH reductase probably contributed to the condition. Fetal haemoglobin is more easily oxidized than adult haemoglobin; further, the delicate skin of the premature neonate is more permeable (Hjelt et al., 1995)