Reaction mass of 2-butylheptanoic acid and 2-ethylnonanoic acid and 2-methyldecanoic acid and 2-propyloctanoic acid

Endpoint summary

Description of key information

In a study performed with 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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to international accepted testing guideline, well documented, category approach

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-12 weeks
- Weight at study initiation: female: 149 - 156 g
- Fasting period before study: 16 - 19 h (access to water was permitted)
- Housing: in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 131113)
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice (lot no. 0801)
- Water: ad libitum, tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days
The animals were non-pregnant and nulliparous.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10x
- 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 (if gavage):10 mL/kg bw
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characterics
- Lot/batch no. (if required): Sigma, lot MKBN871V, expiry date: 30 April 2014
- Purity: not mentioned

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION: 2 g of the test item were suspended in 10 mL of the vehicle. Test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before each dose administration.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg bw, no toxicity was expected.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (3 in each of 2 steps)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing (at least once) during the first 30 minutes and with special attention given during the first 4 hours post-dose. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were weighed on day 1 prior to the administration and on days 8 and 15
- Necropsy of survivors performed: yes, at the end of the observation period the animals were sacrified by an over-dosage of phenobarbital injected intraperitoneally.

Statistics:

not performed

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred throughout the study.

Clinical signs:

other: All animals showed reduced spontaneous activity at 2000 mg/kg bw/d, 3 animals showed additionally piloerection. All animals were competely recovered after 240 minutes.

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.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No animal died. In the study performed the dosis letalis media (LD50) to rats was found to be > 2000 mg/kg bodyweight.

Executive summary:

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. The test item was suspended with cottonseed oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg. All animals used in the study after their entrance at the test facility were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

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. Throughout the 14-day observation period, the weight gain of all animals was within the normal range of variation for this strain. Macroscopic findings of all animals: At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Result: LD50: > 2000 mg/kg bw

Method: OECD 423, EC 440/2008, Method B.1 tris, OPPTS 870.1100

GLP: Yes

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

In the key study, performed with 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 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.

In a second, supporting study with the analogue 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, thus supporting the result of the study with 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.

Justification for classification or non-classification

Reaction mass of 2-butylheptanoic acid and 2-ethylnonanoic acid and 2-methyldecanoic acid and 2-propyloctanoic acid based on the available acute toxicity information does not present an acute oral toxicity hazard and does not require classification according Regulation (EC) No 1272/2008.