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Description of key information

Based on an acute oral and dermal toxicity study (OECD guidelines 423 + 402), it is concluded that the test substance has no acute toxic potential up to the limit dose of 2000 mg/kg in female rats (oral toxicity) and male and female rats (dermal toxicity).

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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan MAFF 8147
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bioassay - Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519; 69120 Heidelberg
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult animals (female animals approx. 10-11 weeks)
- Weight at study initiation: 183-188 g
- Fasting period before study: at least 16 hours before administration
- Housing: Single housing, in Makrolon cages, type III with wooden gnawing blocks
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days before administration
- Microbiological status: SPF

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.27 mL/kg bw

CLASS METHOD:
- Rationale for the selection of the starting dose:
1st experiment: 2000 mg/kg bw as the limit dose
2nd experiment: Because no mortality occurred in the first experiment, a further dose of 2000 mg/kg bw was administered to another group of 3 female animals in the second step.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females in the 1st experiment and 3 females in the 2nd experiment
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weights: Shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Several times on the day of administration and at least once during each workday thereafter.
A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: Yes
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
Statistics:
not performed
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Clinical signs:
Clinical signs in the first 2000 mg/kg bw test group revealed in all animals impaired general state and piloerection from hour 2 until hour 3 or 5 after administration.
Clinical signs in the second 2000 mg/kg bw test group revealed in all animals salivation at hour 0 after administration only.
Body weight:
All animals gained weight in a normal range throughout the study period.
Gross pathology:
There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan MAFF 8147
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bioassay - Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519; 69120 Heidelberg
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult animals (male animals approx. 9 weeks, female animals approx. 13 weeks)
- Weight at study initiation: females: 210-233 g (mean: 222.8 g, SD: 8.7 g); males: 253-276 g (mean: 263.8 g, SD: 9.76 g)
- Housing: Single housing, in Makrolon cages, type III with wooden gnawing blocks
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days before administration
- Microbiological status: SPF

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 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: About 40 cm²
- % coverage: At least 10% of the total body surface

REMOVAL OF TEST SUBSTANCE
- Washing: With warm water
- Time after start of exposure: After 24 hours

TEST MATERIAL
- Amount applied: 2.27 mL/kg bw
- Concentration: Undiluted
- Constant volume or concentration used: Yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (both males and females)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weights: Shortly before application (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Several times on the day of application and at least once during each workday thereafter.
Mortality: At least once each workday
Scoring of skin findings: 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), then several times until the last day of observation.

- Necropsy of survivors performed: yes
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
Statistics:
not performed
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mL/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
Very slight erythema (grade 1) in 5/5 females on day 1 and in 2/5 until day 3
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
All animals gained weight in a normal range throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in any animal examined on the last day of observation (5 males and 5 females).
Other findings:
Local effects
- Males: No local effects were observed.
- Females: Very slight erythema (grade 1) was seen in all female animals on study day 1 and persisted in in two of these animals until study day 3.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

In the chosen key study for acute oral toxicity according to OECD TG 423 (Acute Toxic Class Method) and GLP (BASF SE 2020; 10A0493/19X130), a dose of 2000 mg/kg bw of undiluted Neova was administered by gavage to two test groups of three fasted Wistar rats each (6 females). The following test substance-related clinical observations were recorded, clinical signs occurred within the first 5 hours after administration:

2000 mg/kg (first test group):

- No mortality occurred

- Impaired general state in all animals

- Piloerection in all animals

2000 mg/kg (second test group):

- No mortality occurred

- Salivation in all animals

All animals gained weight in a normal range throughout the study period. There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females). The acute oral LD50 was assessed to be > 2000 mg/kg bw in rats.

 

Acute dermal toxicity

In the chosen key study for acute dermal toxicity according to OECD TG 402 and GLP (BASF SE 2020; 11A0493/19X131), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped application site (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed in the animals. Very slight erythema (grade 1) was noted in all female rats only and occurred within the first 3 days after application. All animals gained weight in a normal range throughout the study period. No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females). Accordingly, the acute dermal LD50 was determined to be >2000 mg/kg bw in male and female rats.

Justification for classification or non-classification

The present data on acute oral and dermal toxicity do not fulfill the criteria laid down in regulation (EU) 1272/2008, and therefore, a non-classification is warranted.

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