nickel(2+) disodium 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Peer reviewed publication in Am. J. of Ind. Medicine. Main author is an authority in research of nickel poisoning. Detailed monitoring of workers accidentally exposed to toxic leves of Ni.

Data source

Reference

Reference Type:

publication

Title:

Acute Nickel Taxicity in Electroplating Workers Who Accidently lngested a Solution of Nickel Sulfate and Nickel Chloride

Author:

F. Wllliam Sunderman, Jr., MD, Brian Dingle, MD, Sidney M. Hopfer, PhD,
and Thomas Swift, Pho

Year:

1988

Bibliographic source:

American Journal of Industrial Medicine 14:257-266 (1988)

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Concentrations of drinking water containing NiS04 · 6H20 and NiCl2 · 6H20 (1.63 gl!iter), caused by leakage from a Nickel-plating tank, were absorbed by exposed or non-exposed workers.

GLP compliance:

not specified

Test type:

other: Monitoring of workers after accidental exposure to toxic concentrations of Ni in drinking water.

Test material

Test material information

1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

H2O4S.Ni

IUPAC Name:

Nickel (II)sulphate

Specific details on test material used for the study:

The test material was drinking water containing NiS04 · 6H20 and NiCl2 · 6H20 (1.63 gl!iter), caused by leakage from a Nickel-plating tank.

Test animals

Species:

other: human

Sex:

male

Details on test animals or test system and environmental conditions:

Age: 17-36 years

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

Workers drank different volumes of contaminated water during a period of approx. 14 h

Doses:

estimated total intake: 0.5 to 2.5 g Ni2+

No. of animals per sex per dose:

Group A: 21 exposed workers, 18 with symptoms, 10 hospitalized; examined from day 1
Group B: 11 exposed workers, 2 with mild symptoms; examined from day 3
Group C: 11 non-exposed workers on the same production line (control)

Control animals:

yes

Details on study design:

- Duration of observation period following contamination: 5 days
- Frequency of observations: on days 1, 2, 3 & 5
- Examinations performed:
all: - urine: Ni-concentration, creatinine, albumin
- serum: Ni-concentration, urea, creatinine, creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phophatase.
hospitalized workerd (n=10): chest X-ray, electrocardiogram, creatinine clearance, urine total protein, blood leukocyte, platelet and reticulocyte counts, blood hemoglobin, pH, pCO2 and pO2, serum glucose, sodium, potassium, chloride, bicarbonate, bilirubin, calcium, cortisol, prothrombin time, partial thromboplastin time, fibrinogen, fibrin split products
- Other examinations (6 wks after exposure): follow-up studies incl. physical examination, urinalysis, blood hemoglobin, reticulocyte counts

Statistics:

Statistical computations (c.g., linear and exponential regression, analysis of var:iance, Student's t-test, Fisher's exact test, and Mann-Whitney U test) were performed according to Saehs [1.984].

Results and discussion

Effect levels

Key result

Dose descriptor:

LD0

Effect level:

>= 33 mg/kg bw

Remarks on result:

other: The value was calculated considering the highest value of Ni uptaken (2.5 g) and assuming a human weight of 75 Kg

Clinical signs:

other: The following complaints were voiced by the 20 symptomatic workers: nausea (N=15), abdominal cramps or discomfort (N = 14), giddiness (N = 7), lassitude (N = 6), headache (N = 5), diarrhea (N = 4), vomiting (N = 3), shortness ofbreath (N =2), cough (N= 1)

Other findings:

No abnormalities were found by the routine laboratory tests (urinalysis, blood count) performed during the initial clinical evaluations

Any other information on results incl. tables

All subjects became asymptomatic within 3 days postexposure.

Workers with Ni concentrations in urine > 1.5 mg/l were hospitalized and treated by diuresis, thier T1/2 for Ni-removal from serum was 27 h, while T1/2 of non-hospitalized workers was 60 h.

Hospitalized workers showed significantly elevated levels of blood hemoglobin and reticulocyte counts from day 3 postexposure to day 8 (paired t-test:p<0.01).

Mild hyperbilirubinemia developed on day 3 postexposure in two of the subjects.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

1. Direct symptoms of Ni poisoning were comparable to earlier findings and lasted up to 48 h after exposure.
2. The retention t1/2 if Ni in serum did not significantly correlate with the initial concentrations of Ni in the serum.
3. Induced diuresis succesfully decreased the retention t1/2 of Ni in blood serum from 60 h to 27 h.
4. Ni poisoning induced mild erythrocytosis and reticulocytosis.