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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
Study period:
14 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study protocol HLE number P1401, designed to meet the minimum requirements of the OECD Guidelines for testing of Chemicals adopted 12 May 1981 and which have been agreed within the EEC for the Notification of New Substances (EEC Directive 79/831/EEC), with the following exceptions: • The temperature in the exposure chamber ranged between 18 -22 °C (rather than 22 ± 2 °C). • The humidity was between 50-95% (rather than 30-70%). • The sponsor did not require the tissues from animals on this study examining histopathologically. These deviation were not thought to have affected the integrity or outcome of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Study protocol HLE number P1401, designed to meet the minimum requirements of the OECD Guidelines for testing of Chemicals adopted 12 May 1981 and which have been agreed within the EEC for the Notification of New Substances (EEC Directive 79/831/EEC)
Deviations:
yes
Remarks:
• The temperature in the exposure chamber ranged between 18 -22 °C (rather than 22 ± 2 °C). • The humidity was between 50-95% (rather than 30-70%). • The sponsor did not require the tissues from animals on this study examin
Principles of method if other than guideline:
OECD Guidelines for testing of Chemicals adopted 12 May 1981 and which have been agreed within the EEC for the Notification of New Substances (EEC Directive 79/831/EEC), with the following exceptions:
•The temperature in the exposure chamber ranged between 18 -22 °C (rather than 22 ± 2 °C).
•The humidity was between 50-95% (rather than 30-70%).
•The sponsor did not require the tissues from animals on this study examining histopathologically.
These deviation were not thought to have affected the integrity or outcome of the study.
GLP compliance:
yes
Remarks:
The project described in this report was subject to audit/inspection by the independent HLE Quality Assurance Unit for the aspects and at the intervals specified below. The findings of each unit, unless indicated otherwise, were reported to HLE management
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test material, Butane diamine was supplied as a liquid by the sponsor.
A total of about 1 litre was received on 22 June 1983.
The test material was stored at ambient temperature and humidity in the dark.
The purity of the test material was not supplied by the study sponsor. The sponsor has on record a determination of the test materials's stability and therefore did not require HLE to provide a stability assessment.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Test system: Rats, Sprague-Dawly strain; 6 groups of 12 rats (6 ¿ and 6 ¿)(supplier: Bantin and Kingman, Hull), exposed to 0.563, 1.120, 1.401, 1.508 or 5.171 mg/l by inhalation (nose only) and a control group (filtered air) over a period of 4 hours. Exposure was followed by a 14 day observation period.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The oxygen concentration was 21% for control and treated animals on all occasions.
The mean mass median aerodynamic diameters were 1.89, 2.58, 2.66, 2.58, and 3.19 µm for groups 2, 3, 4, 5, and 6 respectively. The flow rate for the control group was 8 l/min at all times, the flow rate for the treated groups ranged between 7 and 8 l/min.




Analytical verification of test atmosphere concentrations:
yes
Remarks:
• The temperature in the exposure chamber ranged between 18 -22 °C (rather than 22 ± 2 °C). • The humidity was between 50-95% (rather than 30-70%). * The oxygen concentration was 21% for control and treated animals on all occasions. The mean mass median a
Duration of exposure:
ca. 4 h
Concentrations:
0, 0.563, 1.120, 1.401, 1.508 or 5.171 mg/l
No. of animals per sex per dose:
6 groups of 12 rats (6 ¿ and 6 ¿)(supplier: Bantin and Kingman, Hull)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: immediately before and after exposure, at day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 1.083 mg/L air
Exp. duration:
4 h
Remarks on result:
other: 95% confidence limits could not be calculated from this data
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 1.348 mg/L air
95% CL:
> 0.909 - < 3.596
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 1.131 mg/L air
95% CL:
> 0.877 - < 1.297
Exp. duration:
4 h
Mortality:
An increase in mortality was recorded with increasing dose levels. No deaths occurred at the lowest concentration used (0.563 mg/l) but 100% mortality was recorded for the highest dose group (5.171 mg/l). A sex difference was also noted with females being more susceptible to the treatment than were the males.
Clinical signs:
Animals in the treated and control groups showed clinical signs associated with restraint in the holding tubes. These signs included ruffled wet fur, gernalised staining and chromodacryorrhoea.
In addition, treated animals developed some or all of the following clinical signs: stained nose, respiratory difficulties, emaciation, cold to touch, lethargy, hunched posture, shivering and vocalisation.
Body weight:
The mean body weights of the control and treated groups were reduced by a similar degree following the 4 hour exposure period.
Although there were no survivors in group 6 and only males surviving groups 4 and 5 at day 14, it was possible to detect a dose-related reduction in body weight gain at day 7 compared with the controls; and the data suggests that the picture was similar at day 14.
Gross pathology:
Seven control rats were unremarkable at necropsy. Five rats had dark foci on the lungs or slight reddening of the surface.
In group 2 all rats survived to study termination. At necropsy 10 of the 12 rats had dark areas on the lung. There were no significant changes in any of the other tissues examined.
In group 3, 4, 5 and 6 more than half of the rats in each group died before study termination. The majority of dead animals had dark or red lungs. There were no consistent changes in other tissues apart from the occasional dark liver or sore tails. Most of the surviving rats had dark or red foci/areas in the lung, but other tissues were generally unremarkable.
The pathology findings suggest that the test material has local effects on the lung, but there were no consistent necropsy findings to indicate any gross systemic toxicity.
Other findings:
A dose-related increase in lung weight and lung/body weight ratios was noted in comparison with the controls. These increases were thought to be attributable to pulmonary congestion produced in response to the irritant effects of the test article.

Any other information on results incl. tables

  Mortality   Deaths     
Group number  Atmophere conc (mg/l)  Males  Females  Total 
control  0/6   0/6  0/12
0.563  0/6  0/6  0/12 
1.120  3/6  4/6  7/12 
1.401  2/6  6/6  8/12 
1.508  4/6  6/6  10/12 
5.171  6/6  6/6  12/12 

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information LC50 (rat, inhalation): 1.131 mg/l , Toxic by inhalation Criteria used for interpretation of results: EU
Conclusions:
Toxic, R23 Toxic by inhalation
Executive summary:

Inhalation study (nose only), Sprague-Dawly rats (6 males, 6 females per dose group).

LC50 (inhalation, rats) = 1.131 mg/l (95% confidence limits: 0.877 – 1.297 mg/l), both sexes

DSD: Toxic, R23 Toxic by inhalation

CLP: H330 Fatal if inhaled

From the range of concentrations used, it was not possible to identify a concentration producing no toxicological effects.