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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study conducted to good scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Long-Term Peritoneal Tissue Response in Rats to Mould-Release Agents and Lubricant Powder used on Surgeon's Gloves
Author:
Pelling D & Evans JG
Year:
1986
Bibliographic source:
Food and Chemical Toxicology, 24(5): 425-430

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of the study was to compare the long-term tissue reaction to talc with that of calcium carbonate. A widely used starch lubricant powder (Bio-Sorb) was included to provide a reference point for comparison.
Following implantation of 50 mg samples of a starch powder or of talc or calcium carbonate mould release agents for gloves, in the peritoneal cavity of rats, the treated animals were killed in groups of 10 after 2, 4, 8, 13, 26 and 52 weeks and were examined. Groups of sham-operated animals were used as controls.
GLP compliance:
no
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium carbonate
EC Number:
207-439-9
EC Name:
Calcium carbonate
Cas Number:
471-34-1
Molecular formula:
CH2O3.Ca
IUPAC Name:
calcium carbonate
Details on test material:
The calcium carbonate used conformed with precipitated calcium carbonate USP and had mean and maximum particle sizes of 0.8 and 5 µm, respectively. It contained less than 0.2% silicate as SiO2.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Olac (1976) Ltd, Bicester, Oxon
- Age at study initiation: 5-6 weeks
- Housing: 5 to a cage in air conditioned rooms
- Diet: Spratt's Laboratory Animal diet No. 1 available ad libitum
- Water: Tap water available ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-25 °C
- Humidity (%): 45-75%

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
unchanged (no vehicle)
Details on exposure:
One scoopful of the appropriate powder sample was scattered over the exposed abdominal viscera of each group of 60 animals and the incisions were then closed.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Exposure: up to 52 weeks
Frequency of treatment:
N/A: Single exposure
Post exposure period:
Up to 52 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg
Basis:

No. of animals per sex per dose:
60 animals/ treatment group
Control animals:
yes, sham-exposed

Examinations

Examinations:
10 animals from each group were killed 2, 4, 8, 13, 26 and 52 weeks after the implant operation. The number, location and size of any peritoneal lesions were recorded and samples of the tissues showing lesions were preserved.

Results and discussion

Details on results:
POST-MORTEM EXAMINATION
Residues of the powder samples and associated tissue reactions appeared as focal lesions scattered over the visceral and parietal peritoneal surfaces. Calcium carbonate appeared as a finely divided dispersion of white granules in irregular clusters clearly visible through the thin overlying film of tissue. The macroscopic appearance of these lesions did not change appreciably with time but beyond 2 week they were not seen in more than half the animals treated with starch and they were seen less frequently towards the end of the study in those treated with calcium carbonate.
Adhesions were common in all the treated groups and were found in almost half of the sham-operated animals. The tissues most frequently involved were the body-wall incision site, the omentum, liver and intestine.
See Table 1

INCIDENCE OF ADHESIONS
An analysis of variance showed no significant effect due to time or time-treatment interaction but there was a highly significant difference between treatments. Talc produced significantly more adhesions than the sham operation and starch at every examination time and more adhesions than calcium carbonate from week 8 onwards. This test did not detect a difference between calcium carbonate and starch at individual examination times.

HISTOPATHOLOGY
2 weeks after treatment with calcium carbonate, foci of the calcium salt were surrounded by a granulomatous reaction. At later stages occasional multi-nucleate giant cells and some fibrosis were seen. With time there was absorption of the mineral, leaving a pale eosinophilic matrix. This change was accompanied by a reduction in the granulomatous reaction, such that by week 13 the granulomas were generally small and formed mainly of a central basophilic or pale-staining core and a thin fibrous capsule with few inflammatory cells. The extent of the inflammatory reaction was further reduced by week 26 and 52. Occasional foci of calcium were enclosed in a fine fibrous capsule. This form of tissue reaction was indistinguishable from some of the mineralised lesions seen following treatment with starch.
The granulomatous reaction induced by starch was characterised at week 2 by central necrosis, a macrophage infiltration and fibrosis with starch granules at the periphery of the lesion. At week 13 there was a reduction in the number of starch granules and a concomitant reduction in the severity of the reaction. Some lesions shoed dystrophic calcification. At week 26 and 52 the lesions were composed largely of a central core of dystrophic calcification invested in a thin fibrous capsule. There was little evidence of starch granules and those present were associated with slight fibrosis.

Any other information on results incl. tables

Table 1: No. of animals with visible focal lesions after implantation

Interval (week)

No. of animals affected/ no. observed after treatment with:

No powder

CaCO3

Talc

Starch

2

0/10

10/10

10/10

9/10

4

1/10

10/10

10/10

5/10

8

0/10

10/10

10/10

4/10

13

0/10

10/10

10/10

4/10

26

0/10

9/10

10/10

4/10

52

0/9

4/10

10/10

5/10

Sham operated control

 

Applicant's summary and conclusion

Conclusions:
Talc produced significantly more adhesions than the other treatments and caused a more severe granulomatous reaction, which persisted. Calcium carbonate and starch powder produced similar numbers of adhesions and in both cases the residues became invested by a thin fibrous capsule. Calcium carbonate appeared a safer material than talc.