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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Absorption and retention of nickel from drinking water in relation to food intake and nickel sensitivity.
Author:
Nielsen GD, Søderberg U, Jørgensen PJ, Templeton DM, Rasmussen SN, Andersen KE, Grandjean P
Year:
1999
Bibliographic source:
Toxicology and Applied Pharmacology 154:67-75.

Materials and methods

Type of study / information:
Acute toxicity and dermal sensitization reactions of nickel ion in nickel-allergic patients with eczema compared to non-nickel-allergic patients (control group) with eczema.
Endpoint addressed:
other: acute toxicity (oral) and skin sensitization
Principles of method if other than guideline:
Study examined the possible differences in dermal sensitization reactivity between nickel-allergic patients with vesicular hand eczema and a control group of patients with a similar type of eczema without nickel allergy after oral exposure to nickel ion.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Ethical approval:
confirmed, but no further information available
Details on study design:
Study 1: Toxicokinetics study - Details provided in IUCLID Section 7.10.5 Nielsen et al. 1999, K2 (Ni ion) - Toxicokinetics

Study 2: Sensiization reaction study: Two age matched (+5 years) groups, each consisting of 20 women with current vesicular hand eczema (pompholyx type) were exposed to nickel ion by a single dose of 12 ug Ni/kg body weight as a solution. The subjects had no history or clinical signs of atopic dermatitis. The nickel-sensitized subjects had a history of dermatitis from skin contact with white metal objects and a positive patch test to 5% nickel sulfate in petrolatum within the last 2 years. The controls had no history of dermatitis from skin contact with white metal objects and had a negative patch test to nickel. The nickel-sensitized group varied in age from 20 to 65 years (median, 39.5 years), while controls were 19-69 years (median, 36.5 years). Body weights were similar in the two groups and varied between 50 and 84 kg (median, 67 kg). If a previous patch testing had not been performed within the last 2 years, retesting for confirmation was performed after termination of the experimental study as described above. Reactions graded + to + + + were considered nickel-sensitized. Prior to the nickel ingestion and daily during the study, all patients were examined clinically by the same dermatologist who was blinded regarding nickel allergy. The status of hand eczema was evaluated according to the following clinical parameters: vesicles, erythema, scaling, and fissures; the number of vesicles was counted on the lateral surfaces of the fingers and on the palm of the hand with the highest number of vesicles. The grading system used the following categories: slight (0-30 vesicles), moderate (31-70 vesicles), or severe (more than 70 vesicles). During the study period, none of the patients took systemic drugs that might influence the eczema. The patients were advised to continue using their skin care product and to increase topical steroid treatment if a flare-up of eczema was noted.

- Number of subjects exposed: 20 nickel-sensitised, 20 control
- Sex: Female
- Age: nickel-sensitised (20-65, median = 39.5 years), control (19-69, median = 36.5 years)
- Race: Not reported
- Demographic information: Not reported
- Other: body weight varied between 50 and 84 kg (median, 67 kg).

ENVIRONMENTAL CONDITIONS: Not applicable
IN-LIFE DATES: Not applicable
Exposure assessment:
measured
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The isotope was dissolved and diluted to a concentration of 500 ug/ml and then further diluted to the final
concentration of 3 ug/ml just before use. This concentration was verified by atomic absorption measurements.

DIET PREPARATION
Study 1: Toxicokinetics study - Details provided in IUCLID Section 7.10.5 Nielsen et al. 1999, K2 (Ni ion) - Toxicokinetics

Study 2:
- Rate of preparation of diet (frequency): The nickel solution (12 ug/kg body wt) was ingested on a Tuesday morning at 9 a.m., and fasting was then maintained for another 4 h.

VEHICLE
- Details on vehicle (water) not reported

HOMOGENEITY AND STABILITY OF TEST MATERIAL: Not reported

STATISTICS:
The Mann-Whitney U-test to test possible differences between the two matched groups of female volunteers.

Results and discussion

Results:
Study 1: Toxicokinetics study - Details provided in IUCLID Section 7.10.5 Nielsen et al. 1999, K2 (Ni ion) - Toxicokinetics

Study 2: Sensitisation study - 17 controls had a slight hand eczema, three had a moderate eczema, and all remained unchanged during the study period. In the nickel-sensitized group, 9 showed a flare-up of symptoms after nickel intake, and they also reported increased use of topical steroids. All exacerbations started within 12 h after nickel administration. A LOAEL of 12 ug Ni ion/kg bw was identified.

Any other information on results incl. tables

Additional results from the Sensitization study:

The first serum sample from the female volunteers and the first 24-h urine sample before nickel administration showed nickel concentrations very similar to the first study. The serum analyses then showed a steep increase during the first couple of hours after nickel ingestion, followed by a decline. By 72 h, the nickel concentrations had not yet returned to the level before nickel ingestion. The highest nickel excretion was seen during the first 3 h after nickel ingestion, and the elimination remained increased 72 h later.

Following nickel ingestion, intercellular nickel concentrations increased by a factor of about eight in both groups. Two individuals showed a slightly lower nickel concentration at the second sampling, but otherwise clear increases were found. The nickel concentration in the cell pellets did not seem to reflect the changes revealed by the other parameters.

Applicant's summary and conclusion

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER