1,4,7,10-tetraazacyclododecane

Endpoint summary

Description of key information

Acute oral toxicity. Key study (001). Test method according to OECD 423. GLP study.

Acute oral toxicity. Key study (002). Test method according to 92/69/EWG, B.1. GLP study.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

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:

1996

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl: (WI) BR

Sex:

male/female

Vehicle:

other: NaCl/Polyoxyl-50-stearate (Myrj53)

No. of animals per sex per dose:

Preliminary sighting study: 3 (male)Preliminary sighting study: 3 (female)Main study: 3 (male)Main study: 3 (female)

Details on study design:

Preliminary sighting study:At 2000 mg/kg 6 of 6 animals died.Main study:200 mg/kg: no abnormal findings occurred

Preliminary study:

Species/strain: rat, Wistar2000 mg/kg bw: Evident toxicity: Y; Mortality: Y500 mg/kg bw: not administered50 mg/kg bw: not administered5 mg/kg bw: not administered<5 mg/kg bw: not administered200 mg/kg bw: Evident toxicity: N; Mortality: NObservations:2000 mg/kg: reddish rhinorrhea and silorrhea in one maleafter 30 min of treatment, additionally slight apathy,incomplete eylid closure, ruffled fur, and abnormalbreathing from ca. 6h after treatment in all males, femaleswithout clinical findings.

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

>= 200 mg/kg bw

Effect level:

200 mg/kg bw

Remarks on result:

other: No. with evident toxicity: 0; No. of deaths: 3; No of animals used:3

Effect level:

200 mg/kg bw

Remarks on result:

other: No. with evident toxicity: 3; No. of deaths: 3; No. of animals used: 3

Effect level:

2 000 mg/kg bw

Remarks on result:

other: No. with evident toxicity: 0; No. of deaths: 0; No. of animals used: 3

Clinical signs:

other: 2000 mg/kg: males: reddish rhinorrhea and silorrhea in one animal after 30 min of treatment, additionally slight apathy, incomplete eylid closure, ruffled fur, and abnormalbreathing from ca. 6 h after treatment in all animals, all animals dead after 24 h

Gross pathology:

2000 mg/kg (males and females): necropsy revealed multifocal reddening in stomach, paleness of spleen, discoloration in lung lobes200 mg/kg (males and females): no abnormal findings

Interpretation of results:

other: Harmful

Remarks:

Migrated information criteria interpretation of results: EU

Conclusions:

Test substance in Wistar rats has a discriminating dose of >=200 mg/kg bw.

Executive summary:

The acute toxicity of test substance was performed according to the OECD 423 (1996) Guideline under GLP conditions.

For this limit test type, an initial concentration of 200 mg/kg bw of tst substance in vehicle ( NaCl/Polyoxyl-50 -stearate (Myrj53)) were administered orally to 3 male and 3 female Wistar rats. Due to the 100% mortality of the initial dose, for the main test a concentration of 200 mg/kg bw concentration was used. The effects of test substance on animals were evaluated using the clinical signs, gross pathology, body weight and necropsy.

Test substance in Wistar rats has a discriminating dose of >=200 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: 92/69/EWG, B.1 "ENGLISH"

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Crl: (WI) Br

Sex:

male/female

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1 % wässerige Carboxymethyl Cellulose

Doses:

200, 500, 1000, 2000 mg/kg bdw

No. of animals per sex per dose:

5 male and 5 female per dose

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

1 022 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

978 mg/kg bw

Mortality:

Male: 200 mg/kg bw; Number of animals: 5; Number of deaths: 0Male: 500 mg/kg bw; Number of animals: 5; Number of deaths: 0Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 232Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 5Female: 200 mg/kg bw; Number of animals: 5; Number of deaths: 0Female: 500 mg/kg bw; Number of animals: 5; Number of deaths: 0Female: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 3Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 5

Clinical signs:

other: "DEUSTCH"Signs of toxicity related to dose levels: Folgende klinische Symptome wurden beobachtet:500 mg/kg: bucklige Haltung, nicht koordinierte Bewegungen.1000 mg/kg: Lethargie, buckliche Haltung, nicht koordinierteBewegungen, struppiges Fell.Die überleb

Gross pathology:

"DEUSTCH"Effects on organs:Makroskopisch post mortem Examinierung der toten Tieren ergab:1000 mg/kg: dunkelrote Verfärbung oder Rötung glandulare Mucosa, Blutungen in der Grenzriefe und Drüsenmagen.2000 mg/kg: Blutungen in dem Thymus, Epithelium vom Vormagen, verdickte Grenzriefe, unregelmäßige Oberfläche von dem Drüsenmagen, Erweiterung von dem Colon."ENGLISH"In the animals which died during the study:1000 mg/kg: dark red discolouration or redness of glandular mucosa, blleding in the glandular stomach.2000 mg/kg: bleeding in the thymus, epithelium of the prestomach, unregularsurface of the glandular stomach, extension of the Colon

LD50 males: 1022 mg/kg

LD50 females: 978 mg/kg

Interpretation of results:

other: Harmful

Remarks:

Migrated information criteria interpretation of results: EU

Conclusions:

Test substance in Wistar rats (male/female) had a LD50 of 1000 mg/kg bdw.

Executive summary:

The acute toxicity of test substance was performed according to the 92/69/EWG, B.1 "English" Guideline under GLP conditions.

Several concentrations of test substance (200, 500, 1000 and 2000 mg/kg bw) in vehicle (CMC) were administered orally to 5 male and 5 female Wistar rats per concentration. The effects of test substance on animals were evaluated using the clinical signs, gross pathology, body weight and necropsy.

Test substance in Wistar rats (male/female) had a LD50 of 1000 mg/kg bdw (1022 m/kg fpr mañes and 978 mg/kg fpr females).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

200 mg/kg bw

Quality of whole database:

Both studies scored Klimisch I

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity. Key study (001).Test method according to OECD 423. GLP study. Limit test type, an initial concentration of 200 mg/kg bw of test substance in vehicle ( NaCl/Polyoxyl-50 -stearate (Myrj53)) was administered orally to 3 male and 3 female Wistar rats. Due to the 100% mortality of the initial dose, for the main test a concentration a 200 mg/kg bw concentration was used. The effects of test substance on animals were evaluated using the clinical signs, gross pathology, body weight and necropsy.

Test substance in Wistar rats has a discriminating dose of >=200 mg/kg bw.

Acute oral toxicity. Key study (002). Test method according to 92/69/EWG, B.1. GLP study.The acute toxicity of test substance was performed according to the 92/69/EWG, B.1 "English" Guideline under GLP conditions. Several concentrations of test substance (200, 500, 1000 and 2000 mg/kg bw) in vehicle (CMC) were administered orally to 5 male and 5 female Wistar rats per concentration. The effects of test substance on animals were evaluated using the clinical signs, gross pathology, body weight and necropsy.

Test substance in Wistar rats (male/female) has a LD50 of 1000 mg/kg bdw.

Justification for selection of acute toxicity oral endpoint:

Both studies provides supplementary data about LD50 and discriminating dose of test substance in Wistar rats.                  

Justification for classification or non-classification

Based on the available information, test substance, in the acute oral toxicity test, is classified as Category 4.