Reaction mass of butanoic acid, 2-ethyl-2,3,3-trimethyl-, ethyl ester and butanoic acid, 2,3-dimethyl-2-(1-methylethyl)-, ethyl ester and pentanoic acid, 2,2,4,4-tetramethyl-, ethyl ester and ethyl 2,2,3,3-tetramethylpentanoate and ethyl 2,2,3,4-tetramethylpentanoate

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

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

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met