Registration Dossier

Toxicological information

Epidemiological data

Currently viewing:

Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1999
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Publication; It has been suggested that there are some 400 other individuals who have not been studied but are known to have similar symptoms, and little is known about the prognosis for affected individuals (no follow up studies have been arranged), although anecdotally many originally affected still have symptoms 11 years later.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incident.
Author:
Altmann P, Cunningham J, Dhanesha U, Ballard M, Thompson J and Marsh F.
Year:
1999
Bibliographic source:
BMJ. 319: 807-11.

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
neurotoxicity
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
To establish whether people exposed to drinking water contaminated with 20 tonnes of aluminium sulphate in the Camelford area of Cornwall in the south west of England in July 1988 had suffered organic brain damage as opposed to psychological trauma only.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Aluminium sulphate

Method

Type of population:
general
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (cohort study): To establish whether people exposed to drinking water contaminated with aluminium sulphate had suffered organic brain damage as opposed to psychological trauma only.

METHOD OF DATA COLLECTION
- Type: Retrospective study of affected people

SETTING: On 6 July 1988, 20 tonnes of aluminium sulphate were accidentally emptied into the treated water reservoir that served 20000 people in the Camelford area of Cornwall in the south west of England.

STUDY POPULATION
- Total number of subjects participating in study: 55 affected people
- Sex/age: 30 women and 25 men, aged 15-¬70 years, mean 41.8 (2.1) years

COMPARISON POPULATION
- Type: Other comparison group: 15 sibling pairs; 15 siblings nearest in age to one of the group but who had not been exposed to the contaminated water were studied.

HEALTH EFFECTS STUDIED
- Disease(s):
- Diagnostic procedure: Standard laboratory techniques were used for routine blood haematology and biochemistry analysis. Aluminium was measured with well-established methods (Altmann et al., 1987; Altmann, 1991), the normal serum concentration being less than 10 µg/L.
- Visual analogue scales were used to score each patient's general appearance and affect and subjects' own views of their symptoms. Two identical visual analogue questionnaires were administered to examine changes in symptoms over time—one concerning symptoms 1 month after the incident (as perceived in retrospect) and one similarly relating to symptoms at the time of investigation.

OTHER DESCRIPTIVE INFORMATION ABOUT STUDY:
Various clinical and psychological tests to determine medical condition and anxiety levels in affected people. Assessment of premorbid IQ (pFSIQ) with the national adult reading test, a computerised battery of psychomotor testing, and measurement of the difference in latencies between the flash and pattern visual evoked potentials in all participants.
Exposure assessment:
estimated
Details on exposure:
TYPE OF EXPOSURE: Accidental exposure

TYPE OF EXPOSURE MEASUREMENT: Biomonitoring (urine) / Biomonitoring blood / other: Clinical assessment, Psychomotor testing, Visual evoked potentials, Effects of anxiety

EXPOSURE LEVELS: 20 tonnes of aluminium sulphate were accidentally emptied into the treated water reservoir that served 20000 people.

POSTEXPOSURE PERIOD: Three years after the incident the study was performed to investigate 55 adults who were considering litigation on account of its alleged effects.

Statistical methods:
Differences between normally distributed group data were analysed by the unpaired or paired Student's t test as well as one factor analysis of variance and non­parametric tests when appropriate. Correlations between different variables were performed by least squares linear regression analysis. In addition, analysis of covariance was used when age was a covariate. Two tail probability (P) values of < 0.05 were regarded as significant. Analyses were performed with StatView for Macintosh (Haycock et al., 1992).

Results and discussion

Results:
- Clinical assessment: All 55 participants complained of short term memory loss and impaired concentration. None had any relevant personal or family history or were taking any form of psychotropic drug or consuming excessive alcohol. The participants' visual analogue scores indicated deteriorating memory and concentration. Physical examination, in particular of the neurological system and visual acuity, yielded normal results in all the participants.

- Psychomotor testing: The mean (SE) pFSIQ was above average at 114.4 (1.1). The most sensitive of the psychomotor tests for organic brain disease was the symbol digit coding (SDC) test (normal score 100, abnormal < 85). Participants performed less well on this test (54.5 (6.0)) than expected from their pFSIQ (P < 0.0001) and a little less poorly on the averaged less discriminating tests within the battery (86.1 (2.5), P < 0.0001). In a comparison with the 15 sibling pairs (affected people's age 41.0 (3.3) years v sibling age of 42.7 (3.1) years (P = 0.36) the exposed people had similar pFSIQ (114.7 (2.1)) to their siblings (116.3 (2.1), (P = 0.59) but performed badly on the symbol digit coding test (51.8 (16.6)) v (87.5 (4.9) for siblings, P = 0.03).

- Visual evoked potentials: The flash­pattern differences in exposed people were greater than in 42 unrelated control subjects of similar age (27.33 (1.64) ms v 18.57 (1.47) ms, P = 0.0002). The 15 unexposed siblings had significantly better flash­pattern differences than their affected siblings (13.4 (2.4) ms v 29.6 (2.9) ms, P = 0.0002).

- Effects of anxiety: Thirty six of the 55 participants studied were available for anxiety testing, which was carried out at a different location and time. The mean SCL90 score was 1.0 (0.1), indicating relatively low levels of anxiety. Those below the median anxiety score (0.8) did not differ from those above it with regard to their symbol digit coding scores or flash­pattern differences. No effect of anxiety could be shown on these measurements from the analysis of the anxiety scores of exposed people.

- Haematology and biochemistry: There were no significant findings. Serum aluminium concentrations were normal, urinary aluminium concentration was increased in one participant, and several current tap water aluminium concentrations were high.
Confounding factors:
Results shown that several abnormalities in people exposed to aluminium and other contaminants in the Camelford incident. Their assessment of symptoms correlated with independent assessments of their general appearance and mental affect, adding weight to the validity of their complaints but throwing no light on the causation.
Strengths and weaknesses:
results show that although the sibling pairs were indistinguishable (paired Student's t test) in terms of age and pFSIQ, the results of both the symbol digit coding tests and the flash­pattern differences were significantly worse (by paired Student t test) in the Camelford participants than in their unexposed siblings.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
People who were exposed to the drinking water contaminated with aluminium sulphate suffered considerable damage to cerebral function, which was not related to anxiety. Follow up studies would be required to determine the longer term prognosis for affected individuals.
Executive summary:

A retrospective study was conducted to establish whether people exposed to drinking water contaminated with 20 tonnes of aluminium sulphate in the Camelford area of Cornwall in the south west of England in July 1988 had suffered organic brain damage as opposed to psychological trauma only. In this study, 55 affected people and 15 siblings nearest in age to one of the group but who had not been exposed to the contaminated water were studied. Various clinical and psychological tests to determine medical condition and anxiety levels in affected people. Assessment of premorbid IQ (pFSIQ) with the national adult reading test, a computerised battery of psychomotor testing, and measurement of the difference in latencies between the flash and pattern visual evoked potentials in all participants.

 

The mean (SE) pFSIQ was above average at 114.4 (1.1). The most sensitive of the psychomotor tests for organic brain disease was the symbol digit coding (SDC) test (normal score 100, abnormal < 85). Participants performed less well on this test (54.5 (6.0)) than expected from their pFSIQ (P < 0.0001) and a little less poorly on the averaged less discriminating tests within the battery (86.1 (2.5), P < 0.0001). In a comparison with the 15 sibling pairs (affected people's age 41.0 (3.3) years v sibling age of 42.7 (3.1) years (P = 0.36) the exposed people had similar pFSIQ (114.7 (2.1)) to their siblings (116.3 (2.1), (P = 0.59) but performed badly on the symbol digit coding test (51.8 (16.6)) v (87.5 (4.9) for siblings, P = 0.03). The flash­-pattern differences in exposed people were greater than in 42 unrelated control subjects of similar age (27.33 (1.64) ms v 18.57 (1.47) ms, P = 0.0002). The 15 unexposed siblings had significantly better flash­-pattern differences than their affected siblings (13.4 (2.4) ms v 29.6 (2.9) ms, P = 0.0002). No effect of anxiety could be shown on these measurements from the analysis of the anxiety scores of exposed people.

 

People who were exposed to the drinking water contaminated with aluminium sulphate suffered considerable damage to cerebral function, which was not related to anxiety. Follow up studies would be required to determine the longer term prognosis for affected individuals.