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Diss Factsheets

Administrative data

Description of key information

No acute toxicity studies of registered substance were available. The registered substance is a complex reaction mixture, containing N,N'-bis(3-aminopropyl)ethylenediamine (CAS No. 10563-26-5) and N-(2-aminoethyl)-1,3-propanediamine (CAS No. 13531-52-7) among others as majors components. These two components were used as surrogate to evaluate the toxicity of the registered substance. For further justification please refer to IUCLID chapter 13.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study report wich meets basic scientific principles, however with the following restriction: Minimal details on test animals were given. For read across justification please refer to IUCLID chapter 13.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
BASF Test:
Several groups of 5 rats were treated by gavage with suspensions of the test substance in 0.5% Carboxylmethyl cellulose (CMC) aqueous preparation. Group-wise documentation of clinical signs was performed over the 14-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The clinical signs and findings were reported in summary form.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males 202 g, females 170 g (mean)
- Diet: Altromin R 124 (Altromin GmbH, Lage)

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Doses:
647, 950, 1397, 2043, 3002 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 140 mg/kg bw
Mortality:
LD50 = approx. 1200 µl/kg bw, corresponding to approx. 1140 mg/kg bw (relative density = 0.95)
Clinical signs:
other: Dyspnoea, poor general state, apathy, abdominal or lateral position, spastic gait, atonia, and diarrhoea were noted in the 1397, 2043 and 3002 mg/kg bw dose groups.
Gross pathology:
Necropsy findings of the animals that died comprised erythema of the intestinal mucosa, acute congestive hyperemia and dilatation of the heart, acute cachexia.

Dose

(mg/kg bw)

 

Mortality

Dead/Treated

1 hour

24 hours

48 hours

7 days

14 days

male

female

male

female

male

female

male

female

male

female

647

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

950

0/5

0/5

0/5

0/5

0/5

0/5

1/5

0/5

1/5

0/5

1397

0/5

0/5

1/5

2/5

3/5

2/5

5/5

4/5

5/5

4/5

2043

0/5

0/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

3002

1/5

0/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 140 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment. For read across justification please refer to IUCLID chapter 13.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only one dose level
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 3,29 kg (mean); female: 3,44 kg (mean)



Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done):

TEST MATERIAL
- Concentration (if solution): 100 %


Duration of exposure:
once
Doses:
200 µl/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
184 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Calculated from 0.2 ml/kg assuming test substance density of 0.92 g/ml
Mortality:
2 male animals and 1 female animal died after 7 days.
Clinical signs:
other: slight apathy in all animals, apathy in 3 animals, urine tinged with blood in 3 of the 3 animals that died
Gross pathology:
- Animals that died spontaneously: Kidney (renal pelvis and urinary bladder filled with blood); Liver (focal mass necroses); lung (severe edema); heart (dilatation bilaterally)
- Animals sacrificed after 14 days: no adverse effects observed
Other findings:
Necrosis was observed in all animals

Mortality

 Dose (µl/kg)  Conc. (%)  No. of Animals died within1 h  24 h  48 h  7 d  14 d
 200  100  3 male  0/3  0/3  0/3  2/3  2/3
 200  100  3 female  0/3  0/3  0/3  1/3  1/3
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
184 mg/kg bw

Additional information

Oral:

Two acute oral studies are available on the single components of N3/N4-crude mix, one conducted with with N,N'-bis(3-aminopropyl)ethylenediamine (BASFAG.XXVI/100; CAS No. 10563-26-5) and one conducted with N-(2-aminoethyl)-1,3-propanediamine (BASFAG.XXVI/99; CAS No. 13531-52-7).

 

In the BASFAG.XXVI/100 study (reliability score: 2), largely conducted equivalent to methods described in OECD guideline 401, the LD50 for oral acute toxicity in rats was calculated as ca. 1140 mg/kg bw. Doses of 647, 950, 2040 and 3002 mg/kg bw of an aqueous solution in carboxymethyl cellulose were applied by gavage followed by a post dose observation period of 8 days. Main clinical signs observed were dyspnoea, poor general state, apathy, abdominal or lateral position, spastic gait, atonia, and diarrhoea, generally noted in the 1397, 2043 and 3002 mg/kg bw dose groups.. At necropsy, findings of the animals that died comprised erythema of the intestinal mucosa, acute congestive hyperemia and dilatation of the heart acute cachexia.

 

In the BASFAG.XXVI/99 study (reliability score: 2), also largely conducted equivalent to methods described in OECD guideline 401, the LD50 for oral acute toxicity in rats was calculated as ca. 654 mg/kg bw. Doses of 464, 1470, 681, 100, 14700 and 4640 mg/kg bw of an aqueous solution in aqua. dest (4.64 to 46.4%) were applied by gavage followed by a post dose observation period of 14 days. Main clinical signs observed were dyspnea, apathy, abdominal position, lateral position, stagger, atonia, tremor, reduced general condition, diarrhoe, spasctic gait as well as initial body weight loss partially or in some animals of all but the low dose group. At necropsy, findings of the animals that died comprised heart dilation, congestive hyperemia in the heart, atonic and dilated stomach, diffuse erythema in the gastro-oesophageal vestibule, as well as dilated gut with bloody diarrhea, observed partially or in all animals of all but the low dose group.

 

Dermal:

In the BASFAG.XXVI/100 study (reliability score: 2), largely conducted equivalent to methods described in OECD guideline 402, the LD50 for dermal acute toxicity in rats was calculated as ca. 190 mg/kg bw. 3 male and 3 female rabbits were shaven on their dorsal side and then treated for 24 h under occlusive conditions using one dose (200 µl/kg

bw, corresponding to 190 mg/kg bw)) of test substance. Animals were observed for 14 days, and those that died during the course of the study were submitted to necropsy. Survived animals at the end of the study were also subjected to gross-pathological examination. 1 rabbit died after 48 hours and 7 days respectively, and 2 rabbits died 14 days after treatment. Main clinical signs observed were Apathy, dispnoea, cyanosis, tremor, piloerection, blood-coloured urine with hematoma and poor general state. At necropsy, the animals that died during the observation period showed nephrosis, acute dilatation and acute hyperemia of the heart, edema appeared in the lung and the kidney were degenerated, whereas no abnormalities were observed on sacrificed animals.

 

The second BASF study BASFAG.XXVI/99 study (reliability score: 2), also largely conducted similar to the first one, and the LD50 for dermal acute toxicity in rats was calculated as ca. 184 mg/kg bw. 2 male animals and 1 female animal died after 7 days. Main clinical signs observed were slight apathy in all animals, apathy in 3 animals, urine tinged with blood in 3 of the 3 animals that died. At necropsy, findings of animals that died spontaneously were: kidney (renal pelvis and urinary bladder filled with blood); liver (focal mass necroses); lung (severe edema); heart (dilatation bilaterally). For the animals sacrificed after 14 days no adverse effects were observed.

 

Inhalation:

No study is available for the derivation of an acute LC50, neither for the test substance, nor for its surrogates. In an Inhalation Risk Test conducted with N-(2-aminoethyl)-1,3-propanediamine (CAS No. 13531-52-7), no mortality was observed when 12 rats were exposed for 8 hours to an atmosphere that has been saturated at 20 degrees centigrade with the volatile part of the compound. Signs of toxicity were attempt to escape, closure eyelid and eye irritation.

However, the mixture will be classified and labeled as harmful after acute inhalation due to the presence of ethanediamine (CAS No. 107-15-3) as a secondary constituent.


Justification for selection of acute toxicity – inhalation endpoint
There are no data available for N3/N4-amine. However, the mixture will be classified and labeled as harmful after acute inhalation due to the presence of ethanediamine (CAS No. 107-15-3) as a secondary constituent.

Justification for classification or non-classification

Based on the above described studies and considering the worst case assumption that the test substance contains 100% of its most toxic surrogate the test substance should be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 as follows:

harmful if swallowed (GHS cat. 4) and fatal in contact with skin (GHS cat. 2)

Moreover, the mixture will be classified and labeled as harmful after acute inhalation (GHS cat. 4) due to the presence of ethanediamine (CAS No. 107-15-3) as a secondary constituent.