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Administrative data

Endpoint:
biochemical or cellular interactions
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
No data
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment (sparse details about material and methods).
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1988

Materials and methods

Principles of method if other than guideline:
Inhibition of alpha1-antitrypsin by Hexamethylene diamine (HMD or 1,6-hexane diamine; HDA) and influence of the phenotype
GLP compliance:
no
Type of method:
in vitro
Endpoint addressed:
respiratory sensitisation

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexamethylenediamine
EC Number:
204-679-6
EC Name:
Hexamethylenediamine
Cas Number:
124-09-4
Molecular formula:
C6H16N2
IUPAC Name:
hexane-1,6-diamine
Details on test material:
- Name of test material (as cited in study report): 1,6-hexane diamine; HDA

Test animals

Species:
human
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
Twenty-six persons (18 healthy blood donors, 5 members of laboratory staff and 3 patients from pulmonary wards)

Administration / exposure

Route of administration:
other: not applicable, as experiments were performed in vitro
Vehicle:
not specified
Details on exposure:
The serum specimens (0.5 mL) were incubated overnight with 0, 1, 2, 2.5, 3, 4 or 5 mM HDA (final concentration) at room temperature.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
Overnight
Frequency of treatment:
Once
Post exposure period:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1, 2, 2.5, 3, 4 or 5 mM
Basis:
no data
No. of animals per sex per dose:
26
Control animals:
yes, concurrent no treatment
Details on study design:
No data

Examinations

Examinations:
In vitro alpha1-antitrypsin activity (see table 1)
Alpha1-antitrypsin phenotype
Positive control:
No

Results and discussion

Details on results:
No data

Any other information on results incl. tables

Table 1: decreased activity of human serum alpha1 -antitrypsin in vitro by 5 mM HDA

Phenotype

N

Control

Treated

Homozygous M

13

1.03 ± 0.15

0.70 ± 0.20

Heterozygous M

7

0.98 ± 0.15

0.48 ± 0.19 **

Heterozygous MS or MZ

4

0.67 ± 0.21

0.36 ± 0.07 **

Homozygous SS or ZZ

2

0.34 ± 0.28

0.16 ± 0.21 **

Each figure represents the mean activity (mg trypsin inhibited x min-1x mL-1)

** Differs from the treated homozygous M at P < 0.01

Applicant's summary and conclusion

Conclusions:
The data suggest that heterozygous antitrypsin carriers may be more susceptible to the effects of inhaled amines, included Hexamethylene diamine, despite their "normal" phenotypic constitution.
Executive summary:

Blood donors and patients from pulmonary wards gave serum specimens for the assay of their alpha1-antitrypsin activity and phenotype. The same specimens were then incubated at the room temperature overnight with increasing concentrations of 1,6-hexane diamine. The 5 mM amine concentration caused a significant decrease in heterozygous antitrypsins (M1 M2, M1 M3, M2 M3 and M1 S) activity while it was less in the homozygous (M1M1 and M2M2) antitrypsin phenotypes. The SS and ZZ phenotypes showed a very low initial activity which was, however, further reduced. Analysis for the antitrypsin protein showed a simultaneous loss of its activity. The data suggest that heterozygous antitrypsin carriers may be more susceptible to the effects of inhaled amines, included HMD, despite their "normal" phenotypic constitution.