Registration Dossier

Administrative data

Description of key information

In an acute oral toxicity study (EU method B.1 & GLP) an LD50 > 2000 mg/kg bw was determined (BASF, 10A0059/951012, 1995).
In an acute dermal study (OECD guideline 402 & GLP) an LD50 > 2000 mg/kg bw was determined (BASF, 11A0059/951013, 1995).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3043/V9Z
- physical state at ambient conditions: solid
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Animal species: rat / wistar / chbb: thom (SPF)
- Animal breeder: Dr. K. Thomae GmbH, Biberach, Germany
- Age of the animals: young adult animals.
- Animal weights at start of the study: animals of comparable weight; (150g - 300g) (+/- 20 % of the mean weight).
- Animal identification: individual identification using cage cards and group identification by tail marking.
- Room temperature/Relative humidity: the animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24 degrees Celsius for temperature and of 30.- 70 % for relative humidity. There were no deviations from these ranges which influenced the results of the study.
- Day/night rhythm: 12 h/12 h (6.00 a.m. - 6.00 p.m./ 6.00 p.m. - 6.00 a.m.)
- Type of cage: stainless steel wire mesh gages, type DK-III (Becker & Co., Castrop-Rauxel, Germany)
- No. of animals per cage: single housing.
- Bedding: no bedding in the gages; sawdust in the waste trays.
- Drinking water: tap water ad libitum per day.
- Diet: Kliba-Labordiaet 343, Klingentalmuehle AG Kaiseraugst, Switzerland, ad libitum.

Analysis of drinking water:
The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the technical services of BASF AG as well as for the presence of germs by a contract laboratory.

Analysis of feed:
The feed used in the study was assayed for chemical and microbiological contaminants.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
FASTING OF ANIMALS:
-16 h before administration of test substance, water available ad libitum

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: aqueous formulation corresponds to physiological medium.
- Stability of test substance: Test substance stable in drinking water for at least 4 days

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance, no pronounced acute oral toxicity was expected. Therefore a dose of 2000 mg/kg bw was selected as starting dose.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were recorded several times at the day of administration and at least once daily thereafter. Animals were weighed at day 0 before administration and once weekly thereafter.
- Necropsy of survivors performed: yes, fasting of animals 16 h before sacrifice
- Other examinations performed: clinical signs, body weight
Statistics:
none
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Female animals: 3 animals displayed impaired general state, dyspnoe, staggering and piloerection. All symptoms were reversible until 3 days post application.
Male animals: no abnormalities.
Body weight:
Normal range. The expected body weight gain has been observed in the course of the study.
Gross pathology:
No abnormalities noted at necropsy of animals sacrificed at the end of the study.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP and guideline study.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3043/V9Z
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
-Animal species: rat / wistar / chbb: thom (SPF)
- Animal breeder: Dr. K. Thomae GmbH, Biberach, Germany
- Age of the animals: young adult animals.
- Animal weights at start of the study: animals of comparable weight; (200g - 300g) (+/- 20 % of the mean weight).
- Animal identification: individual identification using cage cards and group identification by tail marking.
- Room temperature/ Relative humidity: fully air-conditioned rooms. 20-24 degrees Celsius and of 30 -70 % for relative humidity.
- Day/night rhythm: 12 h/12 h (6.00 a.m. - 6.00 p.m./ 6.00 p.m. - 6.00 a.m.)
- Type of cage: stainless steel wire mese cages, type DK-III (Becker & co., Castrop-Rauxel, Germany)
- No. of animals per cage: single housing.
- Bedding: no bedding in tee cages; sawdust in the waste trays.
- Drinking water: tap water ad libitum per day.
- Diet: Kliba Labordiaet 343, Klingenthalmuehle AG Kaiseraugst, Switzerland, ad libitum.

Analysis of drinking water:
The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the tecenical services of BASF AG as well as for the presence of germs by a contract laboratory.

Analysis of feed:
The feed used in the study was assayed for chemical and microbiological contaminants.
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal an dorsolateral parts of the trunk; about 50 cm2
- Type of wrap if used: the bandage consists of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. Kg and Fixomull stretch (adhesive fleece), Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Concentration: 0.5 g/mL
- Constant volume or concentration used: yes, constant concentration
- For solids, paste formed: yes (suspension)

VEHICLE
- Amount applied: 4 mL/kg
- Stability of test substance in vehicle: substance is stable in tap water for at least 4 days in a concentration of 1 mg/mL
Duration of exposure:
single exposure
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals;
- Frequency of weighing: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period).
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No signs of systemic toxicity could be noticed. Cageside observtions did not reveal any signs of toxicity.
The following local effects were reported:
females: 2 animals depicted well-defined erythema at study day 1 and another 2 animals displayed slight erythema. 2 Animals showed scaling at day 7. All signs were fully reversible at day 8.
males: 4 animals displayed well defined erythema at day 1, 1 animal had slight erythema the same day. All signs were fully reversible within 2 days.
Body weight:
The body weights developed in the normal range:
- mean weight male animals: day 0: 276 g; day 7: 291 g; day 13: 241 g
- mean weight female animals: day 0: 233 g; day 7: 234 g; day 13: 241 g
Gross pathology:
No abnormalities were noted at necropsy of animals sacrificed at the end of the study.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP and guideline study.

Additional information

To assess acute oral toxicity of the test item (BASF, 10A0059/941012, 1995) a single dose of 2000 mg/kg bw (vehicle: water) was applied in a limit test according to GLP and EU Method B.1.

No mortality occured within the timeframe of the study and the body weights remained unaffected. Necropsy did not reveal any abnormalities. These results are confirmed by a supporting study using the liquid test item as test substance (BASF, 10A0107/941029, 1995). Overall, under the chosen test conditions, the test item was not toxic after single oral administration:

Oral LD50 > 2000 mg/kg bw

As a second exposure route, acute dermal toxicity was monitored (BASF, 11A0059/951013, 1995). The study applied the Standard Acute Method using a single dose of 2000 mg/kg bw (vehicle: water) in a limit test according to GLP and OECD guideline 402.

No mortality occured within the timeframe of the study, no clinical signs of systemic toxicity were reported and the body weights remained unaffected. Necropsy did not reveal any abnormalities. Test animals displayed local signs of irritation: the majority of males and females displayed well defined erythemas at the site of contact which regressed quicker in males (within 3 days) than in females (within 8 days). Overall, under the chosen test conditions, the test item does not have toxic properties in case of single dermal exposure:

Dermal LD50 > 2000 mg/kg bw

The test item was not assayed for acute inhalative toxicity. However, an acute inhalative study on the structurally closely related compound trisodium nitriloacetic acid (CAS 5064-31-3) does not indicate significant toxicity.

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 (EC) No 1272/2008. The LD50 was greater than 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.