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Description of key information

In a study performed with the test substance 2-butyloctanoic acid the oral LD 50 was > 2000 mg/kg. The similar substance Reaction mass of n-undecanoic-acid and 2-methyl-decanoic-acid and 2-ethyl-nonanoic-acid and 2-propyl-octanoic-acid and 2-butyl-heptanoic-acid the dosis letalis media (LD50) to rats was found to be > 2000 mg/kg bodyweight. Also in the study with the similar substance 2-decyl tetradecanoic acid the LD 50 was > 2000 mg/kg. 
Single dermal application of the similar substance Reaction mass of 2-butylheptanoic acid and 2-ethylnonanoic acid and 2-methyldecanoic acid and 2-propyloctanoic acid to rats at a dose of 2000 mg/kg body weight was associated with no mortality and no signs of toxicity but slight signs of irritation. The dermal LD50 was determined to be > 2000 mg/kg. Also in the supporting study of 2 -decyltetradecanoic acid a LD50 of > 2000 mg/kg was found. Therefore it is likely that in the whole Isocarb-category the LD50 > 2000 mg/kg.

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:
1999-12-09 to 1999-12-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ORGANISMS:
- Source: Harlan Nossan S. r. l., Correzzana (MI), Italy
- Age: approx. 5-6 weeks
- Weight at study initiation: 126-150 g
- Controls: none
Route of administration:
oral: gavage
Vehicle:
other: aqueous solution containing 0.5% (w/v) carboxymethylcellulose
Details on oral exposure:
ADMINISTRATION:
- Doses: single doses of 2000 mg/kg bw
- Volume administered: 10 ml/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Post dose observation period: 14 days
EXAMINATIONS: Observation for clinical signs immediately upon dosing, approx. 1, 2, 4 hours after dosing and daily thereafter. Mortality and morbidity check twice daily. Individual body weights were recorded just prior dosing and 7 and 14 days after.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the 14 day post-dose observation period.
Clinical signs:
Piloerection, hunched posture, salivation, reduced activity, swollen abdomen, difficulty in moving, hairloss on head and red staining on muzzle.
Recovery of clinical signs had occurred by day 2 in females and by day 13 in males
Body weight:
Changes in body weight observed during the period of the study were within the range expected for this strain and age of animal.
Gross pathology:
No abnormalities were found on necropsy of animals performed on tennination of the study.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The lack of mortality demonstrates the LD50 to be in excess of 2000 mg/kg body weight.
Executive summary:

The lack of mortality demonstrates the LD50 to be in excess of 2000 mg/kg body weight.

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:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
On the basis of all evaluated data, the similarity of all category members of the ISOCARB is justified on basis of the physico-chemical properties, toxicological and ecotoxicological profiles. There is convincing evidence that these chemicals possess an overall common category profile.
Reason / purpose for cross-reference:
read-across source
Limit test:
yes
Statistics:
not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality occurred
Clinical signs:
no clinical signs of toxicity
Erythema grade 1 was observed in 1/5 female and 1/5 male animals. Crust was observed in 2/5 female animals. Desquamation was observed in all female and in 4/5 male animals. Scratches were observed in 3/5 animals of each gender.
All signs of irritation were not completely reversible within the observation period.
Body weight:
no significant effects
A slight weight loss was recorded for 2 out of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 was greater than 2000 mg/kg bodyweight in male and female rats.
Executive summary:

Under the conditions of the present study, single dermal application of the Category member 1 Reaction mass of 2-butylheptanoic acid and 2-ethylnonanoic acid and 2-methyldecanoic acid and 2-propyloctanoic acid to rats at a dose of 2000 mg/kg body weight was associated with no mortality and no signs of toxicity but slight signs of irritation. The dermal LD50 was determined to be > 2000 mg/kg Reaction mass of 2-butylheptanoic acid and 2-ethylnonanoic acid and 2-methyldecanoic acid and 2-propyloctanoic acid / kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

In the key study with the target substance 2-butyloctanioc acid, 6 Sprague-Dawley rats (3 male and 3 female) were treated with 2000 mg/kg bw test substance by oral gavage according to OECD guideline 423 in compliance with GLP. No animal died during the study, the clinical findings noted were piloerection, hunched posture, salivation, reduced activity, swollen abdomen, difficulty in moving, hairloss on head and red staining on muzzle. Recovery of clinical signs had occurred by day 2 in females and by day 13 in males. The lack of mortality demonstrates the LD50 to be in excess of 2000 mg/kg body weight.

Additionally a disregarded acute oral study is available (Stillmeadow, Inc., 1996, Report No. 2548 -95), conducted in accordance with OECD TG 401 and the principles of GLP, resulted in LD50 = 1358 mg/kg bw for females and LD50 = 2020 mg/kg bw for males. However, this study was scored only with Klimisch Score 4 and not used for classification purposes as it has significant deficiencies. These are the details:

- One female in the highest dose group had a dosing injury. Although this was not test material related, this fatality was included into the statistics and the LD50 calculation.  

-There was no clear test material related dose/response relationship.

- Although the tested material is an acid, it was applied without vehicle to the rats. The forestomach of rats has approx. pH 5.6, while the human stomach has a pH of < 1-2 and there is no comparable forestomach. The undiluted gavage of the acidic test item might have significantly affected the outcome of the study. A final conclusion is not possible due to limited documentation of necropsy findings and the relevance for human health is questionable.

-The study report does not contain a certificate of analysis for the test item. Therefore, the composition of the tested material is not unambiguously described. As the density of the tested material differs from the density of our REACh registered substance (0.8573 g/mL vs. 0.8876 g/mL), it seems that the test item is not identical/has a different and worse purity than the REACh registered substance and what we really produce.  

In the supporting study, performed with the Source substance 1 Reaction mass of n-undecanoic-acid and 2-methyl-decanoic-acid and 2-ethyl-nonanoic-acid and 2-propyl-octanoic-acid and 2-butyl-heptanoic-acid according to OECD guideline 423 in compliance with GLP, two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. All animals survived until the end of the study with showing slight signs of toxicity on the day of treatment. The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity and piloerection. All animals were completely recovered after 240 min. Result: LD50: > 2000 mg/kg bw.

Under the conditions of another supporting study, a single oral application of the similar substance 2-decyltetradecanoic acid to rats at a dose 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of 2 -decyltetradecanoic acid after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): >5000 mg/ kg body weight.

Therefore in the whole category the oral LD50 was > 2000 mg/kg.

Single dermal application of the Category member 1, Reaction mass of 2-butylheptanoic acid and 2-ethylnonanoic acid and 2-methyldecanoic acid and 2-propyloctanoic acid to rats, at a dose of 2000 mg/kg body weight was associated with no mortality and no signs of toxicity but slight signs of irritation. The dermal LD50 was determined to be > 2000 mg/kg. Also in the supporting study of the Category member 3, 2 -decyltetradecanoic acid, a LD50 of > 2000 mg/kg was found. Therefore it is likely that in the whole Isocarb-category the LD50 is > 2000 mg/kg.


Justification for selection of acute toxicity – inhalation endpoint
waiving: The test substance has very low vapor pressure, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.

Justification for classification or non-classification

2 -Butyloctanoic acid on the available acute toxicity information does not present an acute toxicity hazard and does not require classification according Regulation (EC) No 1272/2008.