1,3-Propanediaminium, N1-[3-[[2-[dimethyl[3-[(2-methyl-1-oxo-2-propen-1-yl)amino]propyl]ammonio]acetyl]amino]propyl]-2-hydroxy-N1,N1,N3,N3,N3-pentamethyl-, chloride (1:3)

Endpoint summary

Description of key information

Acute oral LD50 in rats > 2000 mg/kg (no mortality observed at that dose) when dose adjusted for the purity of the main constituent, i.e. LD50 > 4760 mg/kg for the registered substance, as described in section 1.2, with its impurities and the residual water necessary for the stability.
Acute dermal toxicity in rats > 2000 mg/kg (no mortality observed at that dose) when dose adjusted for the purity of the main constituent without the residual water necessary for stability, i.e. LD50 > 4840 mg/kg bw for the registered substance as described in section 1.2, with its impurities and the residual water necessary for the stability.

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:

From 23 April to 20 May, 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HanRcc: WIST(SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd
- Age at study initiation: 11 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 23/4/2008 To:20/05/2008

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.476 g/mL
- Amount of vehicle (if gavage):10 mL/kg.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females per dosing occasion

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: mortality/clinical signs: 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15
Body weights: On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

No statistics performed

Preliminary study:

No deaths or clinical signs for 3 females dosed at 2000 mg/kg

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: Dose expressed for the main constituent content.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 4 760 mg/kg bw

Based on:

test mat.

Remarks:

as is: Dose of substance as registered (including residual water necessary for the stability)

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study

Gross pathology:

No macroscopic findings were recorded at necropsy.

The median lethal dose of TRIQUAT MONOMER (active ingredient) after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Not classified according to the criteria of Annex VI Directive 67/548/EEC and EU GHS.

Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with TRIQUAT MONOMER by oral gavage administration at a dosage of 2000 mg/kg body weight in terms of the active ingredient. The test item was diluted in vehicle (purified water) at a concentration of 0.476 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period. No clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose of TRIQUAT MONOMER (active ingredient) after single oral administration to female rats, observed over a period of 14 days is: LD₅₀ (female rat): greater than 2000 mg/kg body weight.

Based on the results of this study, the test substance TRIQUAT MONOMER (active ingredient) is not classified according to the criteria of Annex VI of Directive 67/548/EEC and EU GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 760 mg/kg bw

Quality of whole database:

Reliable study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

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:

17-Jul-2009 to 05-Oct-2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study has been performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [SR 813.112.1]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th, 1997 by decision of the OECD Council [C(97)186/Final]. These principles are compatible with Good Laboratory Practice regulations specified by regulatory authorities throughout the European Community, the United States (EPA and FDA), and Japan (MHLW, MAFF and METI).

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HsdHan: WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands, 5960 AD Horst / The Netherlands
- Age at study initiation: fales: 9 weeks, females: 11 weeks
- Weight at study initiation: males: 231.9 g – 263.8 g, females: 188.0 g – 203.6 g
- Housing: during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494, Rosenberg / Germany, imported by Provimi Kliba
AG, 4303 Kaiseraugst / Switzerland) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 15/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimatation period: 17-Jun-2009 to 22-Jun-2009 (one male, one female), 17-Jun-2009 to 23-Jun-2009 (four males, four females)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): between 30-70%,
- Air changes (per hr): 10-15 air changes per hour,
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 23-Jun-2009 To: 08-Jul-2009

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 25 cm2
- % coverage: approximately 10% of the total body surface
- Type of wrap if used: semi-occlusive dressing wrapped around the abdomen and fixed with an elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Due to the correction factor of 2.42 based on the monomer purity. Application volume was adjusted to 4.36 mL/kg (x 1110 mg/ml = 2000 mg/kg).

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 (see Table 1)

Control animals:

not required

Details on study design:

A single animal of each sex was treated first. Since neither severe local effects nor severe systemic symptoms were observed after the 24-hour exposure, the test was completed using the remaining four male and four female animals for an exposure period of 24 hours.
- Duration of observation period following administration: 15 days in group 1, 14 days in group 2
- Frequency of observations and weighing: The male and the female of group 1 were re-shaved on test days 4, 9 and 15 and all animals of group 2 on test day 3, 8 and 14 to facilitate the reading of the local reactions.
- Necropsy of survivors performed: yes
- Other examinations performed: Viability / Mortality, Clinical Signs, Local Dermal Sign, Body Weights

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: Dose adjusted for content of the main constituent, and density.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 840 mg/kg bw

Based on:

test mat.

Remarks:

as is : Dose of substance as registered (including impurities and residual water necessary for the stability)

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs or local dermal signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of TRIQUAT Monomer after single dermal administration to rats of both
sexes, observed over a period of 14 days is: LD50 (rat) greater than 2000 mg/kg body weight

Executive summary:

A group of 1 male and 1 female and a second group of 4 males and 4 females HsdHan: WIST(SPF) rats were treated with TRIQUAT Monomer at 2000 mg/kg by dermal application. The test item was applied undiluted as delivered from the Sponsor at a volume dosage of 4.36

mL/kg, taking into account the purity of the test item of 41.25% (correction factor 2.42) and the test item density of 1.11 g/mL. The application period was 24 hours.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily

during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-

15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study.

No clinical signs or local dermal signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 840 mg/kg bw

Quality of whole database:

Reliable study

Additional information

A reliable study was available for each endpoint (limit tests). No mortality was observed at the dose administered.

The dose administered in the acute oral toxicity study was adjusted for the purity of the main constituent (2000 mg/kg, i.e. 4760 mg/kg for the registered substance described in section 1.2, i.e. including impurities and the residual water necessary for the stability).

The dose administered in the acute dermal toxicity study was adjusted for the purity and density (2000 mg/kg based on purity of the main constituent and density, i.e. 4840 mg/kg for the registered substance as described in section 1.2, i.e. with the impurities and the residual water necessary for stability).

Based on the physico-chemical properties and unlikely aerosol formation, the inhalation route was not considered the most appropriate for the second acute toxicity study.

Justification for selection of acute toxicity – oral endpoint
Study in compliance with current EC method & OECD guidelines and GLP standards

Justification for selection of acute toxicity – inhalation endpoint
Based on the physico-chemical properties and unlikely aerosol formation, the inhalation route was not considered the most appropriate for the second acute toxicity study

Justification for selection of acute toxicity – dermal endpoint
Study in compliance with current EC method & OECD guidelines and GLP standards

Justification for classification or non-classification

Two reliable experimental studies conducted according to the current guidelines provided a LD50 above 2000 mg/kg for both the oral and the dermal routes. No mortality and no clinical signs were observed at that dose. No classification is required according to the EU criteria for classification (CLP Regulation 1972/2008, and EU Directive 67/548/EEC).