Registration Dossier

Administrative data

Description of key information

Oral (OECD 423), female rat: LD50 > 2000 mg/kg bw (limit test; Cut-off value OECD 423: > 5000 mg/kg bw or unclassified)
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:
26 Feb - 16 Mar 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München, Germany
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 8-10 weeks
- Weight at study initiation: step 1: 167-192 g (animals 1-3), step 2: 145-160 g (animals 4-6)
- Fasting period before study: 16-19 h before dosing until 4 h after dosing (access to water was permitted)
- Housing: single housing in IVC cages, type III H
- Diet: Altromin 1324 maintenance diet for rats and mice (Lot No. 1145), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: the vehicle was chosen because of its non-toxic characteristics
- Lot/batch no.: MKBG0088V

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 female animals per step and dose
Control animals:
no
Details on study design:
- Dosing: 4 days after the first group the second group was dosed
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the application) and on days 8 and 15. Clinical examination was made several times on the day of dosing and once daily at the rest of the observation period.
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: According to OECD Guideline 423, Annex 2d, a cut-off value of >5000 mg/kg bw was derived based on a limit test with 2000 mg/kg bw, since no mortality occurred in any step.
Mortality:
No mortality was observed.
Clinical signs:
No signs of systemic toxicity were observed throughout the whole study period in any animal.
Body weight:
Normal weight gain was observed in all animals.
Gross pathology:
No specific gross pathological changes were recorded for any animal.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
10 Jul - 25 Jul 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1987
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München, Germany
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 8-9 weeks (males), 11-12 weeks (females)
- Weight at study initiation: 239-253 g (males), 203-220 g (females)
- Fasting period before study: no data
- Housing: single housing in IVC cages, type III H
- Diet: Altromin 1324 maintenance diet for rats and mice (Lot No. 0906), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: at least 10 cm²
- % coverage: approximately 10%
- Type of wrap if used: gauze-dresssing and non-irritating tape fixed with an additional semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: removed with cottonseed oil
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- For solids, paste formed: no
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the application) and on days 8 and 15. Clinical examination was made several times on the day of dosing and once daily until the end of the observation 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.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortailty occurred.
Clinical signs:
No signs of systemic toxicity were observed throughout the whole study period. No signs of dermal irritation were observed in any animal.
Body weight:
The body weight development of male and female animals was within the expected range.
Gross pathology:
No specific gross pathological changes were recorded for any animal.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral route

Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid was tested for its acute oral toxicity in a study according to OECD guideline 423 and in compliance with GLP in female Wistar rats (Leoni, 2012). The toxicity of the test substance was assessed by stepwise treatment of two groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg bw. No mortality was observed and no signs of systemic toxicity were observed throughout the whole study period in any animal. Thus, a second step was performed dosing further 3 animals with 2000 mg/kg bw. Again no mortality and no signs of systemic toxicity were observed within the 14 day observation period. The body weight gain shown by the treated animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. In conclusion, an experimental LD50 >2000 mg/kg bw was observed for acute oral toxicity. The LD50 cut-off according to OECD 423 guideline is >5000 mg/kg bw or unclassified, respectively.

Dermal route

Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid was tested for its acute dermal toxicity in a study according to OECD guideline 402 and in compliance with GLP in male and female Wistar rats (Leoni, 2012). 5 animals per sex were dermally exposed to 2000 mg/kg bw (limit test) test substance for 24 h under semiocclusive conditions. After 24 h the test substance was removed from the skin with cottonseed oil. No mortality occurred during the study and no toxicologically relevant abnormalities were found at macroscopic post-mortem examination of the animals. The body weight development of male and female animals was within the expected range. No signs of local effects as dermal irritation and no other clinical signs indicating systemic toxicity were observed in any animal. In conclusion, an experimental LD50 > 2000 mg/kg bw was deduced for acute dermal toxicity.

Justification for classification or non-classification

No mortality was observed in acute oral and dermal toxicity studies up to the limit dose, therefore Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid does not meet the criteria for classification for acute toxicity according to Regulation (EC) 1272/2008.