Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
A comparative study of the acute inhalation toxicity of smoke from TiO2-hexachloroethane and Zn-hexachloroethane pyrotechnic mixtures
Author:
Karlsson N, Cassel G, Fangmark I & Bergman F
Year:
1986
Bibliographic source:
Arch. Toxicol. 59(3): 160-166.

Materials and methods

Principles of method if other than guideline:
Sprague-Dawley rats were exposed for 10 min to the test material followed by observations of clinical signs and mortality. After 7 d observation time animals were anesthetized and lungs were examined.
GLP compliance:
no
Test type:
other: Acute Inhalation Toxicity
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc chloride

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ALAB, Sollentuna, Sweden
- Age at study initiation: 60-80 d
- Weight at study initiation: 200-250 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23 °C
- Humidity (%): 50-60 %



Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
other: water
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chamber operated in dynamic mode
- Exposure chamber volume: 8.4L
- Method of holding animals in test chamber: Perspex cylinders
- System of generating particulates/aerosols: Generated from a solution of test material in water (3.7 and 10.3 M with specific gravity 1.3 and 7.1 g/mL) by means of Collision nebulizer
- Method of particle size determination: Cascade impactors of the Battelle type (Mitchell and Pilcher 1959) using a sampling flow of 1L/min

TEST ATMOSPHERE
- Brief description of analytical method used: Particles collected on membrane filters (Millipore, AAWP, pore size 0.45 µm), filters extracted in 4 M HNO3, extract analyzed by flame atomic absorption spectrometer (air-acetylene flame, 213.9 nm)
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Non-uniform
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.3 and 2.6 µm


Analytical verification of test atmosphere concentrations:
yes
Remarks:
flame atomic absorption spectrometer (air-acetylene flame, 213.9 nm)
Duration of exposure:
10 min
Concentrations:
600, 940, 1220 and 1950 mg Zn/m3 (molar ratio of Zn: ZnCl2 is 1:2.1)
No. of animals per sex per dose:
Three
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 d
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, mortality, gross pathology and histopathology
Statistics:
Not reported

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
female
Dose descriptor:
LC50
Effect level:
<= 1 975 mg/m³ air (analytical)
Exp. duration:
10 min
Mortality:
Two animals died at 940 and 1,220 mg/m3 while all animals died at highest dose of 1,950 mg/m3. For details see ‘table 1’
Clinical signs:
other: Respiratory distress including dyspnoea, decreased locomotor activity, laboured breathing, rhonci and rales observed.
Body weight:
Not reported
Gross pathology:
Entire surface of lungs showed discolouration (dark red), varying degrees of congestion, patchy discolouration, oedema and interstitial emphysema
Other findings:
- Histopathology: Atelectasis, hyperaemia and haemorrhages and oedema observed
- Potential target organs: Lungs

Any other information on results incl. tables

Table 1: Acute inhalation toxicity of test material in rats

 Concentration (mg Zn/m3)*  Mortality after exposure during 10 min (number of deaths/exposed)
 600  0/3
 940  2/3
 1,220  2/3
 1,950  3/3

* The molar ratio of Zn: ZnCl2 is 1:2.1

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results, the acute inhalation LD50 of the test material was calculated to be approximately 2,000 mg ZnCl2/m3 in rats.
Executive summary:

A study was conducted in Sprague-Dawley female rats to determine pulmonary injury after acute inhalation exposure to the test material.

Animals were exposed to the test material at a concentration of 600, 940, 1,220 and 1,950 mg Zn/m3 (molar ratio of Zn: ZnCl2 is 1:2.1) for 10 min. Animals showed respiratory distress. Clinical examination of lung showed discolouration (dark red), varying degrees of congestion, patchy discolouration, oedema and interstitial emphysema, atelectasis, hyperaemia and haemorrhages.

Based on the above results, the acute inhalation LD50 of the test material was calculated to be approximately 2,000 mg ZnCl2/m3 in rats.