Reaction products of N,N'-ethane-1,2-diylbis(1,3-propanediamine), cyclohexane, peroxidized 4-butylamino-2,2,6,6-tetramethylpiperidine and 2,4,6-trichloro-1,3,5-triazine

Endpoint summary

Description of key information

The LD50 values in rats for acute oral exposure and in rabbits for acute dermal exposure to the test substance are >5000 mg/kg bw and >2000 mg/kg bw, respectively.

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:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study in compliance with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: about 6 - 9 weeks
- Weight at study initiation: 210-241 grams for males and 200-230 grams for females
- Fasting period before study: 16 - 20 hours
- Housing: 5/sex/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet: Fresh Purina Rat Chow (Diet #5012) was freely available
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: controlled
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

other: 0.2% methyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 33%

DOSAGE PREPARATION (if unusual):
The test article was mixed with 0.2% methyl cellulose to make dosing by gavage possible. The dose was based on the dry weight of the test article.

Doses:

5000 mg/kg body weight

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 1,2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, on days 3 and 7. at death or at termination in the survivors.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the 5000 mg/kg oral dose.

Clinical signs:

other: There were no abnormal systemic signs noted in 9/10 animals. One female had dyspnea, lethargy, emaciation, ataxia and weight loss throughout the study period.

Gross pathology:

Necropsy results were normal in 9/10 animals. Necropsy observation of animal #10-F revealed that the weight loss and abnormal systemic signs were due to a dosing error rather than to an effect of the test article.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

Based on the results of this study, the oral LD50 in rats is greater than 5000 mg/kg.

Executive summary:

In a GLP compliant OECD guideline study, 5 male and 5 female Wistar rats were treated with the test substance by oral gavage administration at a dosage of 5000 mg/kg body weight. The test item was used as a 33% mixture in 0.2 % methyl cellulose. All animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pretest, on days 3 and 7and at termination of the study. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. Instances of transient weight loss were noted in two females. All other animals gained weight normally. There were no abnormal systemic signs noted in 9/10 animals. One female (#10) had dyspnea, lethargy, emaciation, ataxia and weight loss throughout the study period. Necropsy results were normal in 9/10 animals. Necropsy observation of animal #10-F revealed that the weight loss and abnormal systemic signs were due to a dosing error rather than to an effect of the test article. Therefore, the LD50 in the rat was determined to exceed 5000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

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:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study performed under GLP like quality controlled conditions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

no

Remarks:

QAU statement included

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: 2-4 months
- Weight at study initiation: 2.0 - 2.4 kg
- Fasting period before study:
- Housing: 1/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times per week.
- Diet: Fresh Purina Rabbit Chow (Diet #5321) was provided daily.
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: controlled
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

The patch and test article were moistened with saline to enhance contact of the test article with the dose site.

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: 10% of the body surface
- Type of wrap if used: The test article was applied under a 4 layered surgical gauze patch measuring 10 x 15 cm. The torso was wrapped with plastic which was secured with nonirritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed by gentle washing with distilled water.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 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: The animals were observed 1,2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. Body weights were recorded pretest and on days 3,7 and 14 or at death.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the 2000 mg/kg dermal application.

Clinical signs:

other: Instances of mucoid diarrhea, diarrhea and anogenital soiling were the only abnormal systemic signs noted during the study.

Gross pathology:

Necropsy results were normal in 8/10 animals. Soiling of the anogenital area was noted in one animal and lung abnormalities in another.

Other findings:

Dermal Observations: There were no abnormal dermal responses at any observation period up to and including 72 hours. Thereafter, observations were discontinued.

Conclusions:

Based on this study, the dermal LD50 in rabbits was determined to exceed 2000 mg/kg.

Executive summary:

In an acute dermal toxicity study following OECD guideline 402, 5 male and 5 female New Zealand White rabbits were dermally exposed to the test item for 24 hours at a limit dose of 2000 mg/kg body weight. The test article was moistened with saline and applied to the clipped trunk of the animals under a 4 layered surgical gauze patch measuring 10 x 15 cm. The torso was wrapped with plastic which was secured with nonirritating tape. After 24 hours the wrapping was removed and residual test article was washed off with distilled water. All animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. Body weights were recorded pretest and on days 3, 7 and 14 or at death. All animals were examined for gross pathology. All animals survived the 2000 mg/kg dermal application. Body weight changes were normal in 8/10 animals. Two animals lost weight during the second week of the observation period. There were no abnormal dermal responses at any observation period up to and including 72 hours. Thereafter, observations were discontinued. Instances of mucoid diarrhea and diarrhea were the only abnormal systemic signs noted during the study. Necropsy results were normal in 8/10 animals. Soiling of the anogenital area was noted in one animal and lung abnormalities in another. Based on these observations, the dermal LD50 value of the test item was greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

The acute oral toxicity of the test substance was assessed in a GLP-compliant study following OECD guideline 401 (MB Research Labs, MB 97-5875.01, 1997). In the limit test, a single dose of 5000 mg/kg bw in 0.2% methyl cellulose was applied by gavage to five male and five female Wistar rats followed by an observation period of 14 days. No mortalities were recorded. Instances of transient weight loss were noted in two females, all other animals gained weight normally. No clinical signs were recorded except in one female (#10) which suffered from dyspnea, lethargy, emaciation, ataxia and weight loss. Necropsy observation of animal #10 revealed that the weight loss and abnormal systemic signs were due to a dosing error rather than to an effect of the test article. No other abnormalities were noted for the other animals during necropsy. Overall, under the chosen test conditions, the test substance was not toxic after single oral administration: Oral LD50 > 5000 mg/kg bw

Acute dermal toxicity

An acute dermal toxicity study was performed according to OECD guideline No. 402 with 5 male and 5 female New Zealand White rabbits (MB Research Labs, MB 97 -5706.02, 1997). In the limit test, the test article was applied occlusively to the trunk of the test animals for 24 hours at a dose level of 2000 mg/kg body weight followed by an observation period of 14 days. No mortality occurred within the timeframe of the study. Instances of mucoid diarrhea and diarrhea were the only abnormal systemic signs noted during the study. There were no abnormal dermal responses at any observation period, up to and including 72 hours. Body weight changes were normal in 8/10 animals. Two animals lost weight during the second week of the observation period. Necropsy results were normal in 8/10 animals, soiling of the anogenital area was noted in one animal and lung abnormalities in another. Overall, under the chosen test conditions, the test substance does not have toxic properties in case of single dermal exposure: Dermal LD50 > 2000 mg/kg bw

Acute inhalation toxicity

No data available.

Justification for selection of acute toxicity – oral endpoint
guideline study in compliance with GLP

Justification for selection of acute toxicity – dermal endpoint
Guideline Study performed under GLP like quality controlled conditions.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.