Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: inhalation
Remarks:
other: subacute to subchronic
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No GLP. Documentation insufficient for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1947

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rabbits, rats and mice were employed for the study of local and systemic effects of exposure to various concentrations of biphenyl. The animals were exposed for 7 h/d, 5 d/w in 3 separate inhalation experiments in which the number of periods of exposure varied.
GLP compliance:
no
Remarks:
prior to GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): diphenyl
- Analytical purity: pure or technical grade

Test animals

Species:
other: rabbits, rats and mice
Strain:
other: Albino rabbits, Sprague-Dawley rats and unknown strain of mice
Sex:
not specified

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: celite, i.e. diatomaceous earth or kieselgur
Remarks on MMAD:
MMAD / GSD: no data
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Experiment 1: 64 exposures over a period of 94 days
Experiment 2: 46 exposures over a period of 68 days
Experiment 3: 62 exposures over a period of 92 days
Frequency of treatment:
7h/d and 5d/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
Experiment 1: average 0.3 mg/L air (0.14-0.45 mg/L)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
Experiment 2: average 0.04 mg/L air (0.03-0.06 mg/L)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
Experiment 3: average 0.005 mg/L air (0.002-0.008 mg/L)
Basis:
analytical conc.
No. of animals per sex per dose:
Experiment 1: 3 rabbits and 10 rats
Experiment 2: 3 rabbits and 6 rats
Experiment 3: 12 mice and 4 rats
Control animals:
no

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Remarks on result:
not determinable
Remarks:
no NOAEC identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Experiment 1:

Rats: mortality 5/10 (between 29-49th exposure), average weight loss of 5 surviving animals: 20 g, irritation of nasal mucosa.

Rabbits: No mortality, no adverse local or systemic effects.

Experiment 2:

Rats: mortality 1/6 (after 29th exposure), normal weight gain, mucous membrane irritation.

Rabbits: no adverse effects, urinalysis normal.

Experiment 3:

Rats: no adverse effects

Mice: mortality 2/12 (after 38th and 62nd exposure), irritation of upper respiratory tract

General: rabbits and more particularly rats and mice developed severe bronchopulmonary lesions, consisting of acute emphysema, congestion, edema, bronchitis, widespread lobular pneumonia and multiple abscesses of the lungs. There were also relatively minor toxic changes in the liver and kidneys.

Applicant's summary and conclusion

Conclusions:
The maximum safe concentration for the prolonged exposure of rabbits to diphenyl dust (50% on celite) lies somewhere above 0.3 mg/L.
For rats it is between 0.005 and 0.04 mg/L and for mice it is somewhat below 0.005 mg/L.