Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1969
Report Date:
1969

Materials and methods

Principles of method if other than guideline:
Male rats were exposed to 0.08 mg/L OPD via whole-body inhalation for four hours per day for 10 days. Gross and histopathological examinations were performed on 3 rats/group after the last exposure and 14 days post-exposure.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
o-phenylenediamine, purity approximately 98.5-99%

The test material could not be ground to a suitable particle size because of its physical characteristics. Therefore a regular dust exposure was not possible.

Test animals

Species:
rat
Strain:
other: ChR-CD
Sex:
male

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Method of holding animals in test chamber: 16-liter bell jar
- System of generating particulates/aerosols: The material could not be ground to a suitable particle size because of its physical nature. Regular dust exposure was not possible.

A weighed sample was put in a three-neck borosilicate glass flask in a heated (110-130'C) mineral oil bath. Aerosols were prepared with a stainless steel nebulizer submerged into the melt. Nitrogen was blown through the nebulizer to form fine particles. Diluted air and oxygen were added to the stream prior to entering the exposure chamber to give a 20% O2 atmosphere.

U.V. spectrophotometric analysis and filter paper were used to determine concentrations 4-6 times during exposure. Particle size distribution measurements were made with a Monsanto cascade impactor once for each exposure.

- Method of particle size determination: Airborne solids were measured in the exposure chamber by collecting solids of a known air volume on a Fiberglass filter of 0.1 µ pore size.

TEST ATMOSPHERE
- Brief description of analytical method used: 4-hour exposure carried out in a 16-liter bell jar.

Mass Median Diameter Dispersion
2.0-3.2
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 hours per day
Frequency of treatment:
10 days
Doses / concentrations
Dose / conc.:
0.83 mg/L air (analytical)
No. of animals per sex per dose:
6 per dose
Control animals:
other: Mixture of 2.4 L/min N2 + 0.6 L/min O2
Details on study design:
Post-exposure period: 14 days. Six control rats of the same strain and birth date were exposed to a mixture of 2.4 L/min N2 + 0.6 L/min O2 for the same period of time as the test animals.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Not reported

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Not reported

BODY WEIGHT: Yes
- Time schedule: Not reported

Sacrifice and pathology:
Gross and histopathological examinations were performed on 3 rats from each group (test and control) after the last exposure and 14 days post-exposure. Histopathological examination included the lungs, liver, kidney, brain, heart, lymph nodes, spleen, testes, gastrointestinal tract, thymus, thyroid, adrenal, skin, and bone marrow.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
Respiration was abnormal during exposure, but the test rats showed no other evidence of injury. Clinical signs noted during exposure included slight irregular respiration, not responsive to sound (sometimes), face pawing, hypersensitive to touch, mild facial alopecia. No clinical signs were noted during the post-exposure period.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Repeated exposure of a group of rats to 0.08 mg/L of o-phenylenediamine caused decreased growth rate during the period of exposure with normal rate of gain during a 14-day recovery period.
Gross pathological findings:
no effects observed
Description (incidence and severity):
Gross and histopathological examination of rats sacrificed after the last exposure and after the 14-day recovery revealed no evidence of tissue damage.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Gross and histopathological examination of rats sacrificed after the last exposure and after the 14-day recovery revealed no evidence of tissue damage.
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
Gross and histopathological examination of rats sacrificed after the last exposure and after the 14-day recovery revealed no evidence of tissue damage.

Effect levels

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

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

Male rats were exposed to 0.08 mg/L OPD four hours per day for 10 days. Decreased growth rate during the period of exposure was noted with a normal rate of weight gain during a 14-day recovery period. Irregular respiration was noted during the exposure but the rats showed no other clinical evidence of injury. No evidence of tissue damage was observed during the pathological examinations.