6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid, compound with 2,2',2''-nitrilotriethanol (1:3)

Endpoint summary

Description of key information

The substance is of very low acute toxicity with an oral LD50 of greater than 5000 mg/kg body weight. The dermal LD50 of the individual components was determined to be greater than 2000 mg/kg bw each.

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:

1982-06-15 - 1982-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

24 Feb 1987

Deviations:

yes

Remarks:

purity of test material not indicated

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif:RAIf(SPF), F3-crosses of RII 1/Tif X RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 163 - 220 g
- Fasting period before study: overnight
- Housing: groups of 5 animals in Macrolon cages Type 3
- Diet: ad libitum (NAFAG No. 890, NAFAG AG, Gossau, Switzerland)
- Water: ad libitum (tap water)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw

Doses:

5000 mg/kg

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: animals were observed daily for mortality and clinical signs. Weighing was performed on days 1, 7, 14 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

Dyspnoe, exophthalmus, ruffed fur, diarrhoea and a curved body position was observed in some of the animals. All animals had recovered by study day 11.

Body weight:

Body weight gain was normal throughout the study period.

Gross pathology:

No compound related gross organ changes were observed.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Guideline compliant 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:

March 2, 1995 - April 4, 1995

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 1987)

Deviations:

yes

Remarks:

no data on test item purity

GLP compliance:

yes

Remarks:

Short-term Toxicology, CIBA-GEIGY Limited, 4332 Stein / Switzerland

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: young adult
- Weight at study initiation: 218-228 g
- Housing: individual housing in Macrolon cages, type 3
- Diet: NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

Type of coverage:

semiocclusive

Vehicle:

other: 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80

Details on dermal exposure:

TEST SITE
- Area of exposure: an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- Type of wrap if used: gauze patch

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

TEST MATERIAL
- Amount applied: 2000 mg/kg bw; 4 mL/kg bw
- Concentration: 500 mg/mL
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 ml/kg bw

Duration of exposure:

24 hours

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
- Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
- Clinical signs and symptoms: daily
- Frequency of weighing: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred and no clinical signs were observed.

Mortality:

No mortality occurred.

Clinical signs:

No signs of acute dermal toxicity were observed in this study.

Body weight:

Body weight was not affected by treatment (see details in table 1 "Any other information on results").

Gross pathology:

At necropsy, no deviations from normal morphology were found.

Table 1: Mean body weight of male and female rats at day 0, 7, and 14.

	Mean body weight (g) ± sd
Day 0 male	222 ± 3.9
Day 0 female	225 ± 2.3
Day 7 male	265 ± 3.5
Day 7 female	234 ± 7.3
Day 14 male	309 ± 10.6
Day 14 female	243 ± 9.3

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of the test article in rats was determined to be greater than 2000 mg/kg body weight.

Executive summary:

The acute dermal toxicity of the test substance was assessed in a GLP-compliant study following OECD guideline 402. The test article was administered to five rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. No signs of acute dermal toxicity were observed in this study. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the test substance in rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

The substance is a salt which is a reaction product of an acid (triazine compound, CAS 80584-91-2) and a base (triethaonoleamine, TEA, CAS 102-71-6) that retain their ionic character. Under aqueous conditions it is expected to be present in its dissociated form. Therefore, the individual components of the salt are assessed separately. data on the salt itself are also provided, if available.

Acute oral toxicity

CAS 80584-92-5:

In an acute oral toxicity study, groups of Wistar rats (5/sex) were given a single oral dose of the diluted test substance at a dose level of 5000 mg/kg body weight in distilled water. The animals were then observed for 14 days. No mortality was observed in both male and female rats. Animals showed dyspnea, exopthalmus, ruffled fur, diarrhoea and a curved body position. All symptoms had been resolved by study day 11. During necropsy no treatment related changes were observed. A LD50 of above 5000 mg/kg bw was determined.

CAS 80584-91-4:

One key study is available where the acute oral toxicity of the triazine part was investigated. The study was performed in RAIf (SPF) (Ra 25) rats (5 animals per sex and dose) with a limit dose of 5000 mg/kg bodyweight according to OECD TG 401 (adopted 1981). No mortality occurred and no clinical signs were observed during the observation period (14 days). No necropsy findings were reported. In conclusion, the LD50 was determined to exceed 5000 mg/kg body weight.

CAS 102 -71 -6

In an acute oral toxicity study, 5 Sprague-Dawley rats/sex/dose were exposed to 200 - 6400 mg/kg bw TEA by gavage and observed for 7 days. The LD50 was determined to be 6400 mg/kg bw for males and females. No deaths occurred at doses of 5000 mg/kg bw or below. At 200 mg/kg bw, slight agitation was observed up to 4 hours after exposure; at higher doses unsteady, elevated respiration, anancasm to chew, apathy, and reduced grooming was noticed. Two days after exposure, no clinical signs were observed. Gross pathology did not reveal any abnormalities.

Acute dermal toxicity

CAS 80584-91-4

One GLP-compliant key study is available where the acute dermal toxicity of the test article was investigated. The study was performed in RAIf (SPF) rats (5 animals per sex and dose) with a limit dose of 2000 mg/kg bodyweight under semiocclusive conditions for 24 hours, according to OECD TG 402 (adopted 1987). No mortality occurred and no clinical signs were observed during the observation period (14 days). No necropsy findings were reported. In conclusion, the LD50 was determined to exceed 2000 mg/kg body weight.

CAS 102-71-6

In a dermal limit test, rabbits were treated with 2000 mg/kg body weight TEA on the intact or abraded skin and subsequently observed for a 14 -day period. The test substance was either derived from NH3 (92% TEA) or DEA (88% TEA), both containing approximately 6.5% DEA. Mild erythema was observed following exposure to TEA derived from NH3 on the intact or abraded skin, returning to normal on day 6. Moderate erythema was observed following exposure to TEA derived from DEA on the intact or abraded skin, returning to normal on day 10. No mortality was observed, hence the LD50 was > 2000 mg/kg body weight.

Acute inhalation toxicity

no data available

Conclusion

The test article is of very low acute toxicity. The test article itself and its individual components, the triazine part and the amine, were not acutely toxic when administered with high doses. No findings were reported at necropsy. When given dermally, the triazin and the amine compound did not produce toxic signs at the limit dose. The test article is therefore considered to be not acutely toxic.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for acute oral toxicity under Regulation (EC) No 1272/2008.