Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
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:
</font>

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.