Registration Dossier

Diss Factsheets

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
December 2005 - April 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study well documented with detailed methodology

Data source

Reference
Reference Type:
publication
Title:
NovaSil clay intervention in Ghanians at high risk of aflatoxicosis. I. Study design and clinical outcomes
Author:
Afriyie-Gyawu, Ankrah NA, Huebner HJ, Ofosuhene M, Kumi J, Johnson NM, Tang L, Xu L, Jolly PE, Ellis WO, Ofori-Adjei D, Williams JH, Wang JS & Philips TD
Year:
2008
Bibliographic source:
Food Additives and Contaminants, 25(1): 76-87

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
repeated dose toxicity: oral
Principles of method if other than guideline:
A 3 month double-blind and placebo controlled phase IIa clinical trial was conducted in Ghana to investigate the safety, tolerance and aflatoxin-sorption of dietary NovaSil (NS). As a precursor to a human clinical trial with NS in Ghana a short term ( 2 weeks) study was conducted to evaluate the safety and tolerance of NS capsules in 50 helathy human volunteers (Section 7.10.3 Wang 2005)

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
- Name of test material (as cited in study report): NovaSil clay (NS)

Method

Type of population:
general
Subjects:
- Number of subjects exposed: 177
- Sex: Male and female
- Age: 18-58 years
- Race: African
- Demographic information: Ghana
- Known diseases: No history of chronic disease
Ethical approval:
confirmed and informed consent free of coercion received
Route of exposure:
oral
Reason of exposure:
intentional
Details on exposure:
Subjects were randonly divided into three treatment groups: high dose (HD) who recieved 2 capsules containing 500 mg NS, low dose (LD) who received 250 mg NS or placebo (PL) who received 250mg placebo, three times a day over a period of three months. In total the HD and LD groups received 3.0 and 1.5 g NS per day. As a safety precuation, 3.0 g NS was selected as the highest dose since it represented the MED (minimal effective dose) of NS for AFs based on previous animal studies.
Examinations:
After three month sof capsule ingestion subjects were monitored without NS for another month. At the end of the fourth month, participants underwent final physical examinations and blood and urine specimens were collected for analysis. Urine samples were analyzed for an acute biomarker of AF exposure, AFM1. AFB1-albumin adducts, another biomarker delineating long-term exposure to AFs was measured in serum.

Results and discussion

Clinical signs:
Symtoms included nausea, vomiting, diarrhea, abdominal discomfort, heartburn and dizziness. Over 50% of the symptoms occurred during the first two weeks and the rest reported intermittently afterwards until the end of teh study.None of the effects appeared dose dependent or NS-related except for the episode of nausea.
Results of examinations:
In the hematological analysis there were no significant, dose-dependent effects in any of the parameters among the three treatment groups, either before or after the 3 month trial.

Analysis if serum biochemistry indicated isolated statistically significant differences in a few parameters.

Applicant's summary and conclusion

Conclusions:
Results of the study indicate that administration of NS capsules ( 1.5 and 3.0 g day) over a 3 month period was apparently safe, as evidenced by physical examinations, hematological and biochemical parameters.