Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 - 03. 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

1
Chemical structure
Reference substance name:
trans-cyclohexane-1,2-dinitrilotetraacetic acid
EC Number:
236-308-9
EC Name:
trans-cyclohexane-1,2-dinitrilotetraacetic acid
Cas Number:
13291-61-7
Molecular formula:
C14H22N2O8
IUPAC Name:
2,2',2'',2'''-(cyclohexane-1,2-diyldinitrilo)tetraacetic acid
Test material form:
solid: particulate/powder
Details on test material:
Purity: > 99 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Age at order : 6-7 weeks old
Weight range at arrival : 158.4-161.3 grams (The body weight of each individual was within 20% of the group’s mean)
Acclimatisation period : At least 5 days
Veterinary health check : During acclimatisation period
Animals per cage 3 during the study: up to 5 during acclimatisation
Housing : Polisulfone solid bottomed cages measuring 59.5×38×20 cm with nesting material provided into suitable bedding bags
Cage control : Daily inspected and changed as necessary (at least 3 times/week)
Water : Drinking water supplied to each cage via a water bottle
Water supply : ad libitum
Diet : 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
Diet supply : ad libitum throughout the study except for the dosing procedure
Room lighting : Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
Air changes : Approximately 15 to 20 air changes per hour
Temperature range : 22°C±2°C
Relative humidity range : 55%±15%

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous solution of carboxymethylcellulose
Details on oral exposure:
Test item was administered, by gavage, at a dose volume of 10mL/kg using a plastic feeding tube attached to a graded syringe.
Doses:
On the day of dosing (Day 1), the amount of the formulated test item to be administered was calculated for each fasted animal according to body weight. Animals were dosed once only on Day 1.
No. of animals per sex per dose:
3 female animals/group
Details on study design:
Food was removed fromthe cages overnight prior to dosing (Day -1) and was made available approximately 4 hours after dosing.
Animals were observed for clinical signs as indicated below:
– Day of dosing
· Session 1: on dosing
· Session 2: approximately 0.5 hour after dosing
· Session 3: approximately 2 hours after dosing
· Session 4: approximately 4 hours after dosing
– Daily thereafter for a total of 14 days (Session 1).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
other: acute toxicity estimate (ATE)
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
A first group of 3 female animals was initially dosed at 300mg/kg (Group 1, Step 1). No mortality occurred and no clinical signs were observed. A second group of 3 female animals was then dosed at the same dose level (Group 2, Step 2). No death occurred and no clinical signs were noted. A third group, similarly composed, was dosed at 2000mg/kg (Group 3, Step 3). No death occurred and no clinical signs were seen. A fourth group of 3 female
animals was administered at the same dose level (Group 4, Step 4). No mortality occurred and no clinical signs were observed.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Other findings:
No abnormalities were observed at necropsy examination performed on all animals dosed at 300 and 2000mg/kg (Groups 1, 2, 3 and 4) at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute toxicity of CDTA HHQ was investigated following a single oral administration (10mL/kg in 0.5% aqueous solution of carboxymethylcellulose) to the Sprague Dawley rat followed by a 14-day observation period. No mortality occurred and no signs of toxicity were observed in the 6 animals following dosing at 2000mg/kg.These results indicate that the test item CDTA HHQ did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000mg/kg. The lack of mortality demonstrates the acute toxicity estimate (ATE) to be greater than 2000mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would indicate the following:
Classification : No category
Signal word : No signal word required
Hazard statement : No hazard statement required