Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with minor deviations (Animals received partially different exposure concentrations depending on sex.)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Animals received partially different exposure concentrations depending on sex.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ziram technical
- Lot no.: 1208 AB/V 609
- Purity: 98.5%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River, UK
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 244-310g (m), 221-276g (f)

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.96 (m/f), 0.52 (m), 0.1 (m/f), 0.06 (f)
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 0.13 mg/L air
Exp. duration:
4 h
Mortality:
All animals exposed to 0.96 mg/L died or were killed in extremis 120 to 183 minutes after the start of exposure.
Five males were exposed to 0.52 mg/L. Three died 120 to 150 minutes after the start of exposure and one died 50 minutes after completion of exposure. The last male in this group was killed in extremis on day one following exposure. Two hours after completion of exposure to 0.10 mg/L one female was killed in extremis. Three further females died on day one following exposure. There were no deaths in the five females exposed to 0.06 mg/L.
Clinical signs:
other: see remarks on results
Body weight:
Surviving animals exposed to 0.10 mg/L and the females exposed to 0.06 mg/L showed expected bodyweight gain throughout the study.
Gross pathology:
All animals exposed to 0.96 mg/L showed lungs that were haemorrhaged and swollen. One female killed in extremis also showed abnormal redness of the lungs. In several animals reddening of the small intestine was noted. The liver of one female killed in extremis appeared dark.
In the males exposed to 0.52 mg/L haemorrhage and swollen appearance of the lungs were again common. One male killed in extremis showed lungs that were abnormally red, swollen and fluid filled with dark patches. Isolated incidents of dark liver and gaseous distension of the small intestine were also noted.
Following exposure to 0.10 mg/L one female killed in extremis showed clear fluid present around the snout and mouth. The lungs of this animal also appeared haemorrhagic, swollen and fluid filled. Three females that died in this group showed abnormal redness and swollen appearance of the lungs and congestion of the small intestine. The livers of two females appeared dark. No abnormalities were detected in surviving animals.
No abnormalities were observed in the females exposed to 0.06 mg/L at necropsy.

Any other information on results incl. tables

During exposure to 0.96 mg/L animals showed wet fur and decreased respiratory rate. Hunched posture, lethargy, pilo-erection, gasping respiration, ataxia and ptosis were also noted in three animals that were removed from the chamber 183 minutes after the start of the exposure.

The males exposed to 0.52 mg/L showed decreased respiratory rate during exposure. Signs of wet fur, hunched posture, lethargy, pilo-erection, ataxia, ptosis, laboured respiration and pallor of the extremities were noted in two males on removal from the chamber. Additional signs of gasping respiration, noisy respiration and increased salivation were also noted in the one surviving male one hour after completion. On day one additional signs were evident including hypothermia, pallor of the extremities and red/ brown stains around the snout.

During exposure to 0.10 mg/L wet fur and decreased respiratory rate were apparent in many animals. On removal from the chamber all animals showed wet fur and decreased respiratory rate in addition to hunched posture and pilo-erection. Signs of ataxia were noted and one male showed ptosis. Similar signs were noted one hour after completion of exposure with the exception of wet fur only being evident in one female. Isolated incidents of lethargy, laboured respiration, pallor of the extremities and red/brown stains around the snout were noted and animals showed ptosis. On day one following exposure all surviving animals showed hunched posture, pilo-erection and decreased respiratory rate, one male showed red/brown stains around the snout and lethargy was noted in the female survivor. On day two three males appeared normal but noisy respiration was noted in the female. All surviving animals appeared normal by day 7.

The females exposed to 0.06 mg/L showed wet fur and decreased respiratory rate during exposure. On removal from the chamber hunched posture, lethargy, pilo-erection and ptosis were noted and two females showed ataxia. On day one following exposure there were still signs of hunched posture, pilo-erection and decreased respiratory rate and an incident of red/brown stains around the snout. On day two all females appeared normal.

Applicant's summary and conclusion