2-(2-butoxyethoxy)ethyl 6-propylpiperonyl ether

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

secondary source

Title:

The Safety of Piperonyl Butoxide

Author:

Breathnach, R.

Year:

1998

Bibliographic source:

Jones, G.G., Piperonyl Butoxide the Insecticide Synergist, Academic Press, San Diego

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Piperonyl Butoxide

IUPAC Name:

Piperonyl Butoxide

Details on test material:

no data

Test animals

Species:

rat

Strain:

other: Charles River CD

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: 97% of particles were 10 µm or less

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 hours per day, 5 days per week, 13 weeks

Frequency of treatment:

once on five days per week

Doses / concentrations

Remarks:

Doses / Concentrations:
15, 74, 155, 512 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

15

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

NOAEC

Effect level:

155 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: systemic effecst (Hepatotoxicit at higher dose level local effecst (Larynx)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

There were no effects on body-weight gain, food consumption or ocular effects and all animals survived to the end of treatment.

A dose-related increase in nasal discharge, dried material on the facial area and extremities, and anogenital staining in animals at 155 and 512 mg/m³^.

At the high dose increases in the absolute and relative weights of the livers and kidneys were seen. Vesiculation and vacuolation of the hepatocellular cytoplasm was seen in almost all treated animals but tended to be more pronounced in those at the highest level.

 Squamous or squamoid metaplasia of the pseudostratified columnarepithelium of the larynx was seen in several exposed animals and one control female, the severity being greater in animals at the high dose. Similar metaplastic changes were seen in the columnar epithelium lining the ventral diverticulum in several animals at 512 mg/m³and in one female at 15 mg/m³. Hyperplasia and hyperkeratosis of the squamous epithelium normally found in the larynx were seen in a small number of animals at 512 mg/m³. Laryngeal mucosal inflammation was seen in all treated animals and was slightly more severe in animals at the highest dose. All of the changes were considered to be localized responses indicative of irritation rather than systemic toxicity.

 

No systemic toxicity was seen at 155 mg/m³; effects on the liver and kidney were seen at 512 mg/m³.

Applicant's summary and conclusion

Conclusions:

No systemic toxicity was seen at 155 mg/m³; effects on the liver and kidney were seen at 512 mg/m³.
Local effects were most pronounced at the highest dose level.
The overall NOAEC was 155 mg/m³ for local and systemic effects.

Executive summary:

Groups of 15 Charles River CD rats of each sex were exposed by inhalation for 6 h per day, five days per week, for 13 weeks to piperonyl butoxide (purity, 90.78%) at mean analytical concentrations of 15, 74, 155, or 512 mg/m³. There were no effects on body-weight gain, food consumption or ocular effects and all animals survived to the end of treatment. A dose-relate increase in nasal discharge, dried material on the facial area and extremities, and anogenital staining in animalsat 155 and 512 mg/m³.

At the high dose increases in the absolute and relative weights of the livers and kidneys were seen.Local effects larynx was observed and most severe at the highest dose level.

The overall NOAEC was 155 mg/m³ for local and systemic effects.