Icosanoic acid

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: Predicted data

Title:

[R]: 238 mg/kg/day; Estimation for study LOEL for CAS 506-30-9

Author:

Sustainability Support Services (Europe) AB

Year:

2013

Bibliographic source:

QSAR Toolbox version 3.1

Materials and methods

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Icosanoic acid

EC Number:

208-031-3

EC Name:

Icosanoic acid

Cas Number:

506-30-9

Molecular formula:

C20H40O2

IUPAC Name:

icosanoic acid

Details on test material:

- Name of test material (as cited in study report): Eicosanoic acid
- Molecular formula: C20H40O2
- Molecular weight: 312.53
- Substance type:organic
- Physical state:solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose/head only

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Control animals:

not specified

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes

ORGAN WEIGHT : Yes

Results and discussion

Results of examinations

Clinical signs:

not specified

Description (incidence and severity):

salivation, nose discharge, lacrimation.

Mortality:

not specified

Description (incidence):

salivation, nose discharge, lacrimation.

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Liver weight decreased

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

LOEL

Effect level:

238.2 other: mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Liver weight decreased, salivation, nose discharge, lacrimation.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: "study LOEL"
Estimation method: Takes average value from the 3 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" and ("b" and ( not "c") )  )  and "d" )  and ("e" and "f" )  )

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(O)CCCCCCCCCCCCCCCCCCC
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.1

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Polycyclic Aromatic Hydrocarbons OR SN1 >> Nitrenium ion formation OR SN1 >> Nitrenium ion formation >> Nitro Compounds OR SN2 OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Polycyclic Aromatic Hydrocarbons by DNA alerts for AMES, MN and CA by OASIS v.1.1

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.2

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 10.3

Applicant's summary and conclusion

Conclusions:

In a repeated dose toxicity study, the toxic effects of repeated administration of Eicosanoic acid to rat by the inhalative route was evaluated. Rats were given Eicosanoic acid for 28 days at a dose concentration of 238.2 mg/kg bw/day.Decreased liver weight,salivation,nose discharge and lacrimation was observed.Therefore,LOEL(Lowest onserved effect level) for repeated dose toxicity study was considered to be 238.2 mg/kg bw/day for the 28 days study,it is regarded that there is no repeated dose toxicity at concentrations lower than 238.2 mg/kg bw/day when administered by inhalative route.

Executive summary:

WoE Summary ((Repeated dose toxicity : inhalation) )

The LOEL for target chemical Eicosanoic acid (CAS No.: 506-30-9) is estimated to be 238.2 mg/kg bw/day for Wistar rats using the toolbox version 3.1. The data is estimated to be based on the data summarized below

CAS no.	End point	Value	Species	Doses	Duration	Effects	Remarks
117-81-7	LOAEC	5 mg/m³ air (nominal)	Wistar Rats	5 and 25 mg/m3 (nominal conc.)	28 days	Increase in testosterone and in weight of seminal vesicles.
117-81-7	NOAEC	50 mg/m³ air	Wistar Rats	1.0, 0.05 and 0.01 mg/l(nominal conc.)   230, 11 and 2.3 mg/kg for males and 360, 18 and 3.6 mg/kg (estimated daily intake)	28 days	No effects observed on clinical signs and mortality,body weight,haematology,clinical chemistry,organ weights,gross pathology andhistopathology.
26761-40-0	LOEL	139 mg/kg/day	Rat	0.00, 505.00	14 days	Fatty degeneration in liver,cell proliferation,changes in organ structure,macrophages,inflammation .
79-94-7	LOEL	367 mg/kg body wt/day	CD rats	0.00, 2000.00, 6000.00, 18000.00	14 days	Liver weight decreased,salivation,nosedischarge,lacrimation

 

Based on the studies summarized in the above table it can be observed that the low observed effect value (LOAEC and LOEL) varies from 5 mg/m³ air (nominal) to 367 mg/kg body wt/day and no observed effect value (NOAEC) was found to be 50 mg/m³ air.The effect observed on the above doses are-  

* Increase in testosterone and in weight of seminal vesicles.

* Fatty degeneration in liver,cell proliferation,changes in organ structure,macrophages,inflammation .

* Liver weight decreased, salivation, nose discharge, lacrimation.

* No effects observed on clinical signs and mortality, body weight, haematology, clinical chemistry, organ weights, gross pathology and histopathology.

Thus based on the above results it can be concluded that the estimated value for the target substance (506-30-9) is more closed to the LOEL value of the read across substance (CAS : 79-94-7) which is reported as 367 mg/kg body wt/day whereas other LOEL and NOAEC values are extrapolating from the target value and thus the lowest observed effect level (LOEL) for repeated dose toxicity study of target substance when administered by inhalative route in a 28 days study period was considered to be 238.2 mg/kg bw/day,consisting of decreased liver weight,salivation,nose discharge and lacrimation.

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