Registration Dossier

Administrative data

Description of key information

SIKA Hardener LH is the reaction product of the two substances 2,2-Dimethyl-3-lauroyloxy-propanal (CAS no. 102985-93-3, EINECS no. 468-880-2) and Hexamethylenediamine (CAS no. 124-09-4, EINECS no. 204-679-6). Upon contact with water SIKA Hardener LH rapidly hydrolyses, re-forming the original reactants as degradation products, i.e. the aldehyde and amine component. As agreed with the German Authorities (Bundesanstalt für Arbeitsschutz und Arbeitsmedizin, BAuA, see IUCLID section 13) the tests on acute oral and acute dermal toxicity were waived for animal welfare reasons. Instead, available data for hydrolytic degradation products 2,2-Dimethyl-3-lauroyloxy-propanal and Hexamethlendiamine are provided. Testing via the inhalation route was waived, according to REACH Regulation 1907/2006/EEC, Annex VIII, 8.5.2.

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-09-02 to 2004-09-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2004
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: CRL (WI) BR Wistar rats
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CHARLES RIVER (EUROPE) LABORATORIES INC.
- Age at study initiation: Young adult rats, less than 10 weeks old.
- Weight at study initiation:
Step 1: 163, 174, 175 g before the treatment.
Step 2: 160,160, 163 g before the treatment.
- Housing: Group caging (3 animals/cage)
- Acclimation period: 8 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3 °C.
- Humidity (%): 30-70 %
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
other: sunflower oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 2000 mg/kg bw
- Purity: 96.9 %


Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 animals per dose, 3 animals/step.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Aniimals were observed daily for 15 days after dosing. The body weight were measured and recorded on day 0 (beginning of the experiment), on days 7 and 14 with precision of 1 g.
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs:
A careful clinical examination was made continuously for 30 minutes after the application, then 1h, 2h, 3h, 4h, 5h after the treatment and once each day for 14 days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.
body weight:
The body weight were measured and recorded on day 0 (beginning of the experiment), on days 7 and 14 with precision of 1 g.
Statistics:
Not applicable.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical symptoms appeared after the treatment. The behaviour and general state of all six animals were normal during the study.
Body weight:
The mean body weight and body weight gain of the animals treated with 2000 mg/kg bw 2,2-Dimethyl-3-lauroyloxy-propanal were normal during the two-week observation period, similar to which could be expected in untreated animals of the same age and strain.
Gross pathology:
In the three female animals treated in the first step (2000 mg/kg bw), pulmonary emphysema was observed (No.: 1560, 1561,1562).
In the further three female animals treated at the second step (2000 mg/kg bw), pinprick-sized haemorrhages were found in the lungs (No.: 1563, 1564,1565). In animal No.: 1563, hydrometra occurred, as well.
No macroscopic alterations related to the toxic effect of the test item were found.
The pulmonary emphysema and pinprick-sized haemorrhages in the lungscould be most likely attributed to the terminal procedures. Hydrometra is a common alteration, which occurs sporadically in the experimental rats and was regarded as incidental
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, a single oral administration of the test item 2,2-Dimethyl-3-lauroyloxy-propanal caused neither signs of toxicity nor mortality at 2000 mg/kg bw dose.
Executive summary:

The acute toxic class method according to OECD 423 was performed with 2,2-Dimethyl-3-lauroyloxy-propanal. Six female CRL:(WI) BR Wistar rats were treated with 2,2-Dimethyl-3-lauroyloxy-propanal by oral gavage (single application) at a dose level of 2000 mg/kg in sunflower oil. There was no mortality in the study. Based on these findings no further testing was performed. No clinical signs appeared after administration of 2,2-Dimethyl-3-lauroyloxy-propanal at 2000 mg/kg dose level. No effects on mean body weight and body weight gain were noted for these dose groups. Macroscopic alterations due to the toxic effect of the test item 2,2-Dimethyl-3-lauroyloxy-propanal were not found. Based on the results of this test, the acute oral LD50 of 2,2-Dimethyl-3-lauroyloxy-propanal was estimated to be greater than 2000 mg/kg bw in the rat.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
GLP and guideline conform study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-09-14 to 2004-09-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
31 July 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CRL (WI) BR Wistar rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CHARLES RIVER (EUROPE) LABORATORIES INC.
- Age at study initiation: young adult rats, less than 10 weeks old
- Weight at study initiation: male: 248-255 g, female: 172-190 g
- Housing: Individual caging (1 animal/cage)
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: 10 per cent of the total body surface
- Type of wrap: plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex and per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed for a 14 days post-treatment observation period. The body weights of animals were recorded on day 0 (beginning of the experiment), at day 7 and at day 14 with precision of 1 g.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology
Statistics:
Not applicable.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None.
Clinical signs:
None.
Body weight:
No changes in body weight were observed
Gross pathology:
In the male dose group of 2000 mg/kg bw, emphysema (4/5 male, 3/5 female) and pinprick-sized haemorrhages (1/5 male 2/5 female) were observed in the lungs. No macroscopic alterations due to the toxic effect of the test item were found. The pulmonary emphysema and the pinprick-sized haemorrhages observed during the necropsy might be related to the method of anaesthesia and are also observed in untreated (control) animals
Other findings:
None.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the study results the acute dermal median lethal toxicity (LD50) of Aldhyd L in Wistar rat was considered to be greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity study (Limit Test) according to OECD 402 was performed with 2,2-Dimethyl-3-lauroyloxy-propanal. Five male and 5 female CRL (WI) BR Wistar rats were treated (single 24-hour dermal application) with undiluted 2,2-Dimethyl-3-lauroyloxy-propanal at a dose level of 2000 mg/kg bw. None of these animals died. Clinical signs or dermal symptoms were not observed during the 14days post-treatment observation period. No effects on mean body weight and body weight gain were noted for these dose groups. Specific macroscopic alterations related to the toxic effect of the test item 2,2-Dimethyl-3-lauroyloxy-propanal were not found. Based on the results of this test, the acute dermal LD50 of 2,2-Dimethyl-3-lauroyloxy-propanal was estimated to be greater than 2000 mg/kg bw in the rat.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP and guideline conform study

Additional information

SIKA Hardener LH is the reaction product of the two substances 2,2-Dimethyl-3-lauroyloxy-propanal (CAS no. 102985-93-3, EINECS no. 468-880-2) and Hexamethylenediamine (CAS no. 124-09-4, EINECS No. 204-679-6). Upon contact with water SIKA Hardener LH rapidly hydrolyses, re-forming the original reactants as degradation products, i.e. the aldehyde and amine component. As agreed with the German Authorities (Bundesanstalt für Arbeitsschutz und Arbeitsmedizin, BAuA, see IUCLID section 13) the tests on acute oral and acute dermal toxicity were waived for animal welfare reasons. Instead, available data for hydrolytic degradation products 2,2-Dimethyl-3-lauroyloxy-propanal and Hexamethlendiamine are provided. Testing via the inhalation route was waived, according to REACH Regulation 1907/2006/EEC, Annex VIII, 8.5.2.

 

Acute toxicity oral

As agreed with the German Authorities the test on acute oral toxicity was waived for animal welfare reasons. Instead, available data for 2,2-Dimethyl-3-lauroyloxy-propanal and Hexamethlendiamine are provided:

Dimethyl-3-lauroyloxy-propanal: LD50, rat: > 2000 mg/kg bw

Hexamethylenediamine: LD50, rat: 1160 mg/kg bw.

 

Acute toxicity dermal

As agreed with the German Authorities the test on acute dermal toxicity was waived for animal welfare reasons. Instead, available data for 2,2-Dimethyl-3-lauroyloxy-propanal and Hexamethlendiamine are provided:

Dimethyl-3-lauroyloxy-propanal: LD50, rat: > 2000 mg/kg bw 

Hexamethylenediamine: LD50, rat: 1900 mg/kg bw.

 

Acute toxicity inhalation

Testing via the inhalation route was waived, according to REACH Regulation 1907/2006/EEC, Annex VIII, 8.5.2.

 

An acute oral and dermal LD50 value below 2000 mg/kg bw was determined for the hydrolysis product, Hexamethylenediamine. However, the test item SIKA Hardener LH is not considered to be classified due to the following reason:

- SIKA Hardener LH hydrolyzed and releases equivalent amounts of Hexamethylenediamine.

- 0.0099 mol Hexamethylenediamine need to be released from SIKA Hardener LH to reach the LD50 value of 1160 mg/kg bw (acute oral toxicity).

- 0.016 mol of Hexamethylenediamine need to be released from SIKA Hardener LH to reach the LD50 value of 1900 mg/kg bw (acute dermal toxicity).

- 2000 mg/kg bw of SIKA Hardener LH corresponding to 0.003 mol SIKA Hardener LH

- Based on the mass difference of SIKA Hardener LH (649.05 g/mol) and Hexamethylenediamine (116.20 g/mol), a quantity of SIKA Hardener LH must be used which is approximately three times (acute oral) and five times (acute dermal) higher than the limit value of 2000 mg/kg bw to reach a dose of Hexamethylenediamine which consequently leads to classification.

 

Justification for classification or non-classification

Based on data available for acute toxicity, SIKA Hardener LH was not classified and labelled for acute oral and dermal toxicity according to Regulation 1272/2008/EC (CLP).