Fatty acids, C8-10, zinc salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-01-13 to 2012-02-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Fatty acids, C8 -10, zinc salts is a zinc salt of a short-chained fatty acids containing 8 -10 C-atoms. Thus, read-across of data available for zinc salts of short-chained (C8, C12) and longr-chained (C16 -18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of fatty acids, C8 -10, zinc salts. Acute toxicity is addressed with data read-across from relevant zinc soaps (zinc salts of short-chained (C8, C12) and long-chained (C16 -18) fatty acids), including (i) octanoic acid, zinc salt, basic (C8), (ii) zinc dilaurate,(iii) zinc bis[12 -hydroxy-octadecanoate, and (iv) Fatty acids, C16-18, zinc salts,as well as supporting information from slightly soluble/insoluble zinc compounds.

Regarding acute oral toxicity, a reliable GLP study conducted with octanoic acid, zinc salt, basic (C8) is read-across to address this endpoint.
Different reliable studies conducted with different zinc compounds are read-across as supporting information, including (i) zinc oxide; (ii) Fatty acids, C16-C18, zinc salts; (iii) zinc bis [12-hydroxy-octadecanoate]. Based o the lack of an acute toxicity potential of a zinc salt of a similar chained (C8) fatty acid and zinc salts of longer-chained (C16 -18) fatty acids and slightly soluble/insoluble zinc substances, the LD50 for fatty acids, C8 -10, zinc salts was estimated to be greater than 2000 mg/kg bw.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

adopted 2001-12-17

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 30, 2008)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-11-12

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Octanoic acid, zinc salt, basic

EC Number:

291-793-4

EC Name:

Octanoic acid, zinc salt, basic

Cas Number:

90480-58-3

Molecular formula:

C16H30O4Zn

IUPAC Name:

Octanoic acid, zinc salt, basic

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source: Charles River Laboratories, Research Models and Services, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 167 - 182 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: during the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet (ad libitum): commercial diet, ssniff R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS:
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Air changes: 12 to 18- fold air change per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.8% aqueous hydroxypropylmethylcellulose

Details on oral exposure:

VEHICLE
- Methocel; batch no. 11 A 27-N27, Fagron GmbH & Co., 22885 Barsbüttel, Germany

MAXIMUM DOSE VOLUME APPLIED: the administration volume was 10 mL/kg bw.

DOSAGE PREPARATION: the test substance was diluted to the appropriate concentration in the vehicle.

Doses:

2000 mg/ kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of animals which died prematurely would have been carried out as soon as possible after exitus.
Histopathology was not carried out as no macroscopical findings were noted at autopsy.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: mortality: 0/6, no signs of toxicity

Mortality:

No death was recorded within the test period.

Clinical signs:

other: Under the present test conditions, a single oral administration of 2000 mg octanoic acid, zinc salt, basic/kg bw to female rats did not reveal any signs of toxicity.

Gross pathology:

No pathological changes were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats) > 2000 mg/kg b.w.
According to the EC-Regulation 1272/2008, the test item is not classified as acute toxic via the oral route.