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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Scientific publication with limitations (e.g. concentrations not analysed, small number of animals, limited documentation)

Data source

Reference
Reference Type:
publication
Title:
Nasal mucosa changes after acute and long-term exposure to dicumylperoxide
Author:
Hansson AH, Petruson B
Year:
1986
Bibliographic source:
Acta Otolaryngol (Stockh) 101, 102-113

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
50 µl of a 10 or 25 ppm concentration was placed three times daily in the right nostril
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Percumyl
- Source: Unifos AB, Stenungsund, Sweden

Test animals

Species:
rabbit
Strain:
other: Swedish landrace
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
other: application of 50 µl in the right nostril
Vehicle:
other: phosphate buffered saline
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
4 weeks with 8 weeks recovery
Frequency of treatment:
Three times daily for 5 days a week
Doses / concentrations
Remarks:
Doses / Concentrations:
10 & 25 ppm
Basis:
other: concentration in applied solution
No. of animals per sex per dose:
2 - 6
Control animals:
yes

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Changes in the nasal mucosa after exposure to dicumylperoxide at concentrations of 10 and 25 ppm were studied in rabbits. Albino Swedish rabbits were exposed to dicumylperoxide or to a dust (mixture of fine polyethylene, dicumylperoxide and an antioxidant). Both were applied to the right nostril 3 times a day for 5 days per week at a concentration of 10 or 25 ppm in a quantity equal to 50 µl of solution. Animals were exposed for 4 weeks and allowed to recover for 8 weeks with periodic examinations beginning after 1 hr. Signs of local irritation or damage were observed. Biopsies of the nasal mucosa were studied by light and transmission electron microscopy and by scanning microscopy. After 1 hr an increase amount of mucus containing red blood cells were seen. After 1 week exposure to either 10 ppm dicumylperoxide or 25 ppm dust an increase number of blood vessels was seen in some animals and aggregates of mucus with erythrocytes were found in all animals. At 1 month there were visible blood vessels on the medial and lateral sides of the nasal cavity not seen in unexposed rabbits. Exposure to dust at 10 ppm for 1 month did not result in any apparent changes in the mucosa. After instillation of dicumylperoxide or the dust at 25 ppm for 1 month and a 2 month recovery, visible blood vessels were still observed and there was increase crusting and mucus in the nasal cavities of all rabbits. Scanning electron microscopy showed distortion of many cilia beginning as early as 1 hr after exposure. At 5 days areas lacking cilia but still covered with microvilli and areas with clusters of goblet cells appeared. Changes in the mucosa were more pronounced at 1 month with scattered islands without cilia in the mucosal carpet. Only partial recovery was apparent at 2 months after exposure terminated.

Applicant's summary and conclusion

Conclusions:
Exposure to dust at 10 ppm for 1 month did not result in any apparent changes in the mucosa of albino swedish rabbits.