Reaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcohols

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50: > 2000 mg/kg bw (limit test)

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:

23 Mar - 19 Apr 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

adopted in 1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAGE® Labs, Emment, ID, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Weight at study initiation: 178 - 218 g (range)
- Fasting period before study: overnight prior to dosing; feed was replaced approx. 3 - 4 h after dosing
- Housing: individually in suspended stainless steel cages
- Diet: Envigo Teklad Global 16% Protein Rodent Diet® #2016, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 8 or 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 38 - 63
- Air changes (per hr): 13
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30% (w/w)

Doses:

Step 1 and 2: 2000 mg/kg bw

No. of animals per sex per dose:

3 females per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality, signs of toxicity and behavioural changes 30 min post-dosing, during first several hours after dosing and thereafter once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 7 and 14 prior to scrifice.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study period.

Clinical signs:

other: No clinical signs or abnormal behaviour were observed in any animal.

Gross pathology:

No gross abnormalities was observed in any animal.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study in rats a LD50 value of > 2000 mg/kg bw was derived.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch Score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

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:

20 Mar - 04 Apr 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Schwabach, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 - 10 weeks (males range) and 12 - 13 weeks (females range)
- Weight at study initiation: 250 - 261 g (males range) and 214 - 233 g (females range)
- Housing: individually in IVC cages type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water: tap water, sulphur acidified to a pH value of approximately 2.8, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

other: The test item was moistened with sterile water.

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10%
- Type of wrap if used: The test item was held in contact with the skin by a semi-occlusive dressing consisting of a porous gauze and non-irritating tape that was fixed with an additional dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was removed using sterile water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- For solids, paste formed: yes; test item was moistened with sterile water

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made at least once during the first 30 min post-dose and several times during the first 4 h post-dose. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Signs of erythema and oedema were assessed using the scoring system (Table 2) laid down in OECD Guideline 404. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was oberved during the study period.

Clinical signs:

other: No signs of acute systemic toxicity or signs of local dermal irritation were observed in any animal.

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Other findings:

All animals treated with the test item showed a yellow discolouration at the application site during the whole observation period, due to residual test item.

Table 1. Absolute body weights (bw) in g and body weight change in %

Dose: 2000 mg/kg body weight
Animal No. / Sex	g Day 1	g Day 8	g Day 15	% Day 1-15
21 / male	261	289	324	24
22 / male	250	276	305	22
23 / male	260	291	325	25
24 / male	255	280	303	19
25 / male	258	293	328	27
26 / female	223	220	229	3
27 / female	233	220	230	-1
28 / female	214	224	231	8
29 / female	215	212	216	0
30 / female	217	212	217	0

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute dermal toxicity study a LD50 value > 2000 mg/kg bw in male and female rats was found.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch Score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute oral toxicity ofReaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcoholswas assessed in a study according to OECD guideline 423, EU Method B.1 tris and in compliance with GLP (Lowe, 2018a). An initial limit dose of 2000 mg/kg bw was administered to 3 healthy female rats by oral gavage. Due to the absence of mortality in these animals, 3 additional females were dosed at the same dose level. The Animals were observed for mortality and for general clinical signs, on the day of administration and once daily thereafter for 14 days. Body weights were recorded prior to administration and on Days 7 and 14. A Macroscopic examination was performed at terminal sacrifice on Day 14. All the animals survived the test substance administration and gained body weight during the observation period. There were no clinical signs or abnormal behavior. No gross abnormalities were noted for any of the animals during necropsy. Based on the results of this study, the oral LD50 value was determined to be > 2000 mg/kg bw in rats.

 

Dermal

The acute dermal toxicity ofReaction product of 1,3,5-Triazine-2,4,6-triamine, polymer with formaldehyde, methylated and C16-18 fatty alcoholswas assessed in a limit test performed in 5 male and 5 female Wistar rats according to OECD guideline 402, EU Method B.3 and in compliance with GLP (Niklas, 2018a). The test substance was applied at a single dose of 2000 mg/kg bw to a shaved dorsal area of the trunk of the animals and was held in contact with the skin using a semi-occlusive dressing for 24 h. The Animals were observed daily for mortality, general clinical signs and for skin irritation effects in the administration area (erythema and/or oedema) for a 14-day period. Body weights were recorded on Day 1 (prior to application) and on Day 8 and 15. A Macroscopic examination was performed at terminal sacrifice on Day 14. None of the animals died and no clinical signs were noted. No local skin irritation or alterations on the administration area were observed. All animals showed yellow discolouration at the application site during the whole observation period due to residual test item. A slight weight loss of 1-5% was recorded for 4 out of 5 female animals during the first week, still apparent in 1 out of 5 female animals during the second week. The effects are considered treatment-related and possibly toxicologically relevant. The male animals showed normal weight gain during the first and the second week of the observation. No pathological findings were observed at necropsy. Based on the results of this study, the LD50 value for acute dermal toxicity was determined to be > 2000 mg/kg bw in rats.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are, therefore, conclusive but not sufficient for classification.