Registration Dossier

Administrative data

Description of key information

Irritation:


- skin: corrosive
- eye: corrosive
- respiratory irritation: irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25. Oct 1956 - 19. Nov 1956
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
BASF-Test:
Two animals were treated for 1, 5 or 15 min using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid test substance. The animals were observed for 3 weeks and skin changes were recorded daily. For a final evaluation, the findings from 24 and 48 hours from the raw data were taken into account.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.6 kg (mean)
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal served as control
Duration of treatment / exposure:
1, 5 and 15 min
Observation period:
3 weeks
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): conc. Lutrol and 50 % Lutrol solution
- Time after start of exposure: 1, 5 or 15 min post exposure
Irritation parameter:
erythema score
Remarks:
15 min exposure
Basis:
mean
Time point:
other: 24 h - 48 h (72 h reading missing)
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 3 weeks
Remarks on result:
other: After 15 min exposure single haemorrhages occurred. After 8 days bean-sized crusts were seen. At the end of the observation period (3 weeks) increased hair growth was noted.

Mean erythema score after 24 and 48 (animal1/animal 2). 72 h reading is missing.

 Exposure time  same day  24 h  48 h  72 h  8 days  3 weeks
 1 min  1/0 1/0  1/1 -/-  0/0  0/0
 5 min  1/1 2/0 2/2  -/-  0/0 0/0 
 15 min  3/2 2/2 2/2 -/-  0/0  0/0

The original BASF grading was converted into the numerical grading according the OECD Draize system.

After 15 min exposure single haemorrhages occurred. After 8 days bean-sized crusts. At the end of the observation period (3 weeks) increased hair growth was noted.

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25. Oct 1956 - 07. Nov 1956
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
BASF-Test:
50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3h on the day of treatment and up to 14 days afterwards. Findings were recorded every 2-3 days. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The report describes findings after 1 and 24 hours and at the end of the observation period.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.57 kg (mean)
Vehicle:
unchanged (no vehicle)
Controls:
other: The adjacent eye served as saline control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 drop
Duration of treatment / exposure:
14 days
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
2
Irritation parameter:
other: conjunctiva findings
Time point:
other: after 10 minutes up to 6 days
Reversibility:
not reversible
Remarks:
in fact, at the end of the observation period evaluation of the eyes was not possible because of suppuration
Remarks on result:
other: brown-reddish discoloration of the conjunctiva with bloody secretion
Irritation parameter:
other: chemosis
Time point:
other: after 10 minutes up to 6 days
Reversibility:
not reversible
Remarks:
in fact, at the end of the observation period evaluation of the eyes was not possible because of suppuration
Remarks on result:
other: slight chemosis
Irritation parameter:
other: corneal findings
Time point:
other: after 10 minutes up to 6 days
Reversibility:
not reversible
Remarks:
in fact, at the end of the observation period evaluation of the eyes was not possible because of suppuration
Remarks on result:
other: Opacity
Irritation parameter:
other: Eye lense
Time point:
other: after 10 minutes up to 6 days
Reversibility:
not reversible
Remarks:
in fact, at the end of the observation period evaluation of the eyes was not possible because of suppuration
Remarks on result:
other: welling up of the eye lenses

The application of the test substance caused severe, irreversible corrosion. After 10 min up to 6 days brown-reddish discoloration of conjunctiva, bloody secretion, opacity and slight chemosis was noted. At the end of the observation period evaluation of the eyes due to suppuration not possible. Welling up of eye lenses.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

6 skin irritation/corrosion studies are available, one of validity 1 (Huntsman-PH PH 420-TX-009-92), 3 of validity 2 (BASF-VI/396, Huntsman-PH 420-TX-010-84 and Smyth-1962), and 2 of validity 4 (Hoechst-1979 and Bayer-1979). In almost all of the above studies, the test substance was corrosive to the rabbit skin or caused severe skin burns.

In the BASF study, the primary skin irritation evaluated with undiluted 3-aminopropyldimethylamine, at exposure times of 1, 5 and 15 min caused slight to moderate erythema of the dorsal rabbit skin. 15 min after exposure single haemorrhages occurred which expanded to bean size crusts after 8 days. At the end of the observation period (3 weeks) no clinical signs, but increased hair growth was noted.  

In the Huntsman study of validity 1 performed according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion), 0.5 mL undiluted test substance was applied to the shaved or abraded skin site for 3 min (upper dorsal site for shaved skin) or 60 min, 4 and 24 hours (upper trunk site for shaved skin) of 6 NZW rabbits, secured with semi-occlusive patch and washed out with water and gauze. The skin reaction was evaluated according to the Draize scoring system. The test substance was severely irritating to corrosive at both the 4 and 24 h exposures.

Eye irritation:

In a primary eye irritation study in rabbits, 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals and caused corrosive effects. After 10 min up to 6 days brown-reddish discoloration of conjunctiva, slight chemosis, bloody secretion and irreversible corneal opacity were observed (BASF-VI/396; reliability score 2).

In a second study the test substance corroded the cornea completely (no further data given, Bayer 1979; reliability score 4). A further publication confirmed these severe corrosive effects (Smyth et al. 1949; reliability score: 2).

Respiratory irritation:

In an acute inhalation toxicity study in rats, the animals exposed to 4.31 mg/L for 4 hours exhibited distinct eye irritation at the day of exposure, which regressed during the recovery period (corneal stipplings, fundus not visible). In this study there were also indications that the test substance causes local irritation to exposed tissues, including the respiratory tract (BASF SE, 1310655/897052, reliability score: 1).

In a field study and a subsequently performed cross-sectional study with serial examinations in workers at the same factory, impaired respiration as a result of occupational exposure to DMAPA was noted. Assemblers, a group with the greatest exposure to the epoxy resin system, reported acute symptoms on exposure and showed statistically significant pulmonary function loss over both Monday and the week. Other groups with less exposure in the mold room showed changes intermediate between the assemblers and an unexposed control group. Lung function of all individual assemblers decreased over Monday and over the week, suggesting that the airway response was due to an irritant effect rather than hypersensitivity, as in the latter case a large variation of individual responses might be expected. The impaired respiration observed after DMAPA exposure was considered to be attributed to respiratory irritation by DMAPA, as already expected based on the mucous membrane effects noted in the eyes and as these effects were already observed after single exposure (Brubaker et al., 1979, reliability score: 2, details see section 7.10 Exposure related observations in Humans). Noteworthy to mention, that OECD QSAR toolbox indicated no alert for respiratory sensitization (for details see Read Across Justification in section 13).


Justification for classification or non-classification

Classification, Labelling and Packaging Regulation (EC) No 1272/2008

The substance is already listed in Annex VI to Regulation (EC) No 1272/2008 and classified as Skin Corr Cat. 1B (H314:"Causes severe skin burns and eye damage"). The available experimental data are reliable and support this official classification under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179.

In addition, based on findings in the acute inhalation toxicity studies in rats, but predominantly on Human field and cross-sectional studies with serial examinations, the substance should also be classified as respiratory irritant with STOT SE CAT. 3 and labeled with H335 ("May cause respiratory irritation") under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179.