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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study, no deficiencies

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
m-phenylenebis(methylamine)
EC Number:
216-032-5
EC Name:
m-phenylenebis(methylamine)
Cas Number:
1477-55-0
Molecular formula:
C8H12N2
IUPAC Name:
1,3-phenylenedimethanamine
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): m-Xylylendiamin
- Physical state: Liquid
- Stability under test conditions: Stable (report No 05L00082)
- Storage condition of test material: Room temperature under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Stated in report
- Age at study initiation: 7-9 weeks (m) 10-13 (f)
- Weight at study initiation: 212 - 288g (m) 191 - 216g (f)
- Fasting period before study: Not stated
- Housing: Individually Type DK III cages
- Diet (e.g. ad libitum): KLIBA mouse/rat laboratory diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%):30-70%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:03 Feb 2005 - 02 Mar 2005

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: INA 20
- Exposure chamber volume: 55L
- Method of holding animals in test chamber: Glass tubes
- Source and rate of air: compressed air, 1.5 m3/hr
- System of generating particulates/aerosols: Continuous infusion pump Perfusor VII, Two component atomizer Mod. 970
- Method of particle size determination: Stack Sampler Mark III

TEST ATMOSPHERE
- Brief description of analytical method used: Air sampler GS 312 (DESAGA), Gas Chromatography
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
0.74, 1.35, 5.2 mg/L
Mass median aerodynamic diameter between 1.8 and 3.5 µm
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Week days, twice daily. Weekend, daily. Weight, weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 1.34 mg/L air (analytical)
Based on:
test mat.
95% CL:
ca. 0.99 - ca. 4.34
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 1.38 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 1.16 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All male and female animals died at 5.2 mg/l, two of five males and three of five females died at 1.35 mg/l and one of five females but no males died at 0.74 mg/l, respectively. The lethality's occurred until study day 3
Clinical signs:
other: Clinical signs of toxicity in animals exposed to 0.74 mg/l comprised visually accelerated respiration, pulmonary respiration sounds, squatting posture, piloerection and contaminated fur. Findings were observed from h0 of exposure until including study day
Body weight:
The mean body weights of the animals increased throughout the study period
Gross pathology:
Test group 1 (0.74 mg/l)
No gross pathological abnormalities were noted in the female animal that died 1 day after exposure. However, necropsy findings of 2 males sacrificed at termination of the study comprised diffuse red discoloration and edema of all lung lobes and diffuse red discoloration of all lung lobes in 3 males and 4 females.

Test group 2 (1.35 mg/l)
No gross pathological abnormalities were noted in the animals necropsied at termination of the post exposure observation period and in 2 female animals that died during exposure and 1 male and 1 female animal that died 1 day after exposure.
The following gross pathological abnormality was detected in 1 male animal that died 2 days after exposure: diffuse red discoloration of all lung lobes.

Test group 3 (5.2 mg/l)
Necropsy findings of the animals that died during exposure (4 males and 4 females) comprised diffuse red discoloration of all lung lobes with partly sunken surface. The animal body showed wet fur and white contamination in the region of the head.
Necropsy findings of the 2 animals (1 male and 1 female) that died after exposure (d2; d3) comprised red discoloration of all lung lobes, partly focal. The animals showed slight red discoloration of content of the small intestine and moderate dilatation was seen in the small intestine or in the large intestine of the male animal, additionally.

Any other information on results incl. tables

Clinical signs of toxicity in animals exposed to 1.35 mg/l comprised visually accelerated respiration, pulmonary respiration sounds, squatting posture, piloerection, exsiccosis, reduced general state and smeared and contaminated fur. Findings were observed from h0 of exposure until including study day 14. The mean body weights of the surviving male animals increased throughout the study period. The mean body weights of the surviving female animals decreased during the first post exposure observation week but increased during the second week. No gross pathological abnormalities were noted in the animals necropsied at termination of the post exposure observation period, in two female animals that died during exposure and 1 male and 1 female animal that died 1 day after exposure. The following gross pathological abnormality was noted in 1 male animal that died 2 days after exposure: diffuse red discoloration of all lung lobes. The clinical signs of toxicity in animals exposed to 5.2 mg/l were comparable to test group 2 (1.35 mg/l). Gasping, formation of nasal crusts and apathy in 1 male and 1 female animal were observed additionally. Findings were observed from hour 0 of exposure until including study day 1.

No body weight development of the male and female animals could be determined because all animals died within 3 days after exposure. Necropsy findings of the animals that died during exposure (4 males and 4 females) comprised diffuse red discoloration of all lung lobes with partly sunken surface. The animal body showed wet fur and white contamination in the region of the head. Necropsy findings of the 2 animals (1 male and 1 female) that died after exposure (d2; d3) comprised red discoloration of all lung lobes, partly focal. The animals showed slight red discoloration of content of the small intestine and moderate dilatation was seen in the small intestine or in the large intestine of the male animal, additionally. Under the conditions of this study the LC50 for male and female rats after liquid aerosol inhalation was calculated to be 1.34 mg/l.

 

Mean body weights (g)

 

Test concentration mg/L

Day 0 

Day 7 

Day 14 

 Male

0.74 

241.6

250.3 

287.0 

 Female

0.74

216.7 

224.8

245.4 

 Male

1.35

212.6

22.3 

262.6 

 Female

1.35 

191.7 

179.9 

196.4 

 Male

5.2

288.3 

-

 Female

5.2 

211.3 

 

Mortality

Concentration (mg/L)

0.74

1.35

5.2

Mortality

 Male

0

2

5

 Female

1

3

5

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The combined LC50 is 1.34 mg/L
The LC50 was found to be 1.16 mg/L for female animals and 1.38 mg/L for male animals