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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Six rats per group were exposed via whole body inhalation for four hours to 1.4, 1.6, 2.6, 4.2, 4.8, and 10.2 mg/L. Rats were observed and weighed during a post-recovery period. Gross and histopathological examinations were conducted for rats exposed to 1.6 and 2.6 mg/L. Several rats exhibiting hindquarter paralysis were also sacrificed at various time point post exposure.
GLP compliance:
no
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ortho-Phenylenediamine.
- Purity: 98.5-99%
The material as received was partially oxidized.

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 u 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 test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
1.6, 1.4, 2.6, 4.2, 4.8, and 10.2 mg/L
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: Observations were reported at various doses between 14-48 days.
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology and pathology.

Rats were sacrificed at 1, 2, and 7 days after exposure to 1.6 mg/L and 14 days after exposure to 2.6 mg/L. One rat dying during exposure to 10 mg/L was also necropsied for gross and histopathological examinations. Two rats having hindquarter paralysis were sacrificed at 18 and 19 days post-exposure to 4.8 and 4.2 mg/L, respectively. Two rats recovering from hindquarter paralysis from the same exposures at 46-48 days post-exposure were necropsied and examined for gross and histopathological examinations.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 3.6 mg/L air (nominal)
95% CL:
ca. 2.5 - ca. 5.2
Exp. duration:
4 h
Mortality:
(Filter - Mortality)
1.4 - 2/6 (Deaths occurred on the first day)
1.6 - 1/6 (Death occurred on the second day of recovery)
2.6 - 1/6 (Death occurred on the fifth day of recovery)
4.2 - 3/6 (One death on the second day and two on the third day post-exposure) One rat was sacrificed on the 19th day post-exposure. Another one was kept 48 days and then sacrificed
4.8 - 3/6 (Two died on the first day post-exposure, one died the second day after exposure)
10.2 - 6/6 (Three died one day post-exposure, one died two days post-exposure, and one died three days post-exposure, on died on the fourth day post-exposure)
Clinical signs:
other: 1.4 mg/L: During exposure - irregular breathing, not responsive to sound, gasping. Post-exposure - very hypersensitive, vicious, yellow fur 1.6 mg/L: During exposure - irregular breathing, occasional grooming. 2.6 mg/L: During exposure - irregular br
Body weight:
1.4 mg/L: Around 10% weight losses the first day

1.6 mg/L: Around 10% weight losses the first day

2.6 mg/L: Around 10% weight losses the first day

4.2 mg/L: 10-15% weight losses the first day. Two surviving rats had slight weight gains through third, fourth, and fifth days. Lost weight next five days.

4.8 mg/L: 10-15% weight losses. Two rats continuously lost weight throughout the 14 days

10.2 mg/L: Surviving rat had approximately 15% body weight losses on the first day post-exposure and continued to lose weight four days after the exposure.
Gross pathology:
Microscopic evidence of irritation to the respiratory apparatus and a suppression of sperm formation. Microscopic evidence of damage to the testicular germinal epithelium when sacrificed at 7, 14, 18, and 46 days.

Microscopic examination of animals with hindquarter paralysis showed atrophy of the muscles in the hind legs but no microscopic evidence of injury to the nerves. There was still some evidence of muscle atrophy and slight inanition after 48 days.

Applicant's summary and conclusion

Conclusions:
4-hour LC50 (rats): 3.6 mg/L
Executive summary:

Six rats per group were exposed via whole body inhalation for four hours to 1.4, 1.6, 2.6, 4.2, 4.8, and 10.2 mg/L. Rats were observed and weighed during a post-recovery period. Gross and histopathological examinations were conducted for rats exposed to 1.6 and 2.6 mg/L. Several rats exhibiting hindquarter paralysis were also sacrificed at various time point post exposure.

The 4-hour LC50 was calculated to be 3.6 mg/L. Rats exhibited tremors and hindquarter paralysis post-exposure. Pathological examinations revealed evidence of irritation to the respiratory apparatus and a suppression of sperm formation. A delayed hindquarter paralysis, which healed spontaneously, but slowly, was observed.