Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: pre-GLP, no guideline

Data source

Reference
Reference Type:
publication
Title:
Response of rats to repeated inhalation of ethylenediamine vapours
Author:
Pozzani, U.C , Carpenter C.P
Year:
1954
Bibliographic source:
Industrial hygiene and occupational medicine,9,1954,223-225

Materials and methods

Principles of method if other than guideline:
Four exposure groups of 30 rats (15 female/15 male) were exposed to EDA vapour. Each exposure group had a control group.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylenediamine
EC Number:
203-468-6
EC Name:
Ethylenediamine
Cas Number:
107-15-3
Molecular formula:
C2H8N2
IUPAC Name:
ethane-1,2-diamine

Test animals

Species:
rat
Strain:
Sherman
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Chamber air was passed through an acidified glassbead adsorption tube. The captured Ethylenediamine was quantified by titration.
Duration of treatment / exposure:
6 weeks
Frequency of treatment:
7 h/day, 5 days/week
No. of animals per sex per dose:
15 male and 15 female
Control animals:
yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
59 ppm (analytical)
Sex:
male/female
Basis for effect level:
other: clinical signs; body weight; organ weights;
Dose descriptor:
NOAEC
Effect level:
144 mg/m³ air (analytical)
Sex:
male/female
Dose descriptor:
NOAEL
Effect level:
48 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: Recalculated using rat weight 0.425 kg (mean male/female) and inhalation volume 0.33 m3/7h (values from guidance document)
Dose descriptor:
LOAEC
Effect level:
132 ppm
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LOAEC
Effect level:
323 mg/m³ air (analytical)
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
107 mg/kg bw/day (actual dose received)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

132 ppm: The death of 4/30 animals was attributed to lung infection (not substance-related); slight depilation; body weight gain and relative weights of liver and kidney were not affected; no substance-related macroscopic or histologic changes.

225 ppm: The death of 16/30 was substance-related and another 10 death were considered not to be substance-related; the 4 rats which survived showed significantly lower weight gain and higher relative weights of liver and kidney; cloudy swelling of the liver and of the loop and convoluted tubules of the kidney; lung congestion was observed in exposed as well as in control rats in similar proportions.
484 ppm: All rats died within 20 days of initial exposure; depilation was first observed on the 6th day of exposure; cloudy swelling of the liver (in 23/28 animals), cloudy swelling and degeneration of convoluted tubules (in 7/28 animals); congestion of the lung (in 17/28 animals) and of the adrenal cortex (in 5/28 animals).
59 ppm: No effect on weight gain or organ weights. No depilation. No significant damage to examined tissues; lung, liver and kidney.

Applicant's summary and conclusion

Conclusions:
NOAEC in a subacute inhalation study was 144 mg/m³ air .
Executive summary:

In a 6 week study four exposure groups of 30 Sherman rats (15 female/15 male) were exposed to EDA vapour 7 h /day for 5 days per week. Each exposure group had a control group. The NOAEC was 144 mg/m³ air