Registration Dossier

The substance Eicosanoic acid does not exhibit repeated dose toxicity by the oral,inhalation and dermal route.

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

The prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Remarks:

Doses / Concentrations:
1500 mg/kg bw
Basis:

Control animals:

not specified

Observations and examinations performed and frequency:

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

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:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

OTHER FINDINGS : No effects observed on morphology and reproduction.

Dose descriptor:

NOEL

Effect level:

1 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No effects observed on the following parameter: mortality,bodyweight ,food consumption ,reproduction,morphology.

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL,LOAEL,NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" or "f" ) and "g" ) and (("h" or "i" or "j" or "k" or "l" or "m" ) and ("n" and ( not "o") ) ) and (("p" or "q" or "r" or "s" or "t" or "u" ) and ("v" and ( not "w") ) ) ) and "x" ) and "y" ) and ("z" and "aa" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid moiety AND Neutral Organics by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Anionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acid moiety AND Neutral Organics by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups (nested) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Anionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acid moiety AND Neutral Organics by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups (nested) ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Acid anhydrides OR Acylation >> Direct acylation involving a leaving group >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> Diacylperoxides OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> N-acylated heteroaromatic amines OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Thioesters OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Diarylesters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR Ionic OR Ionic >> Electrostatic interaction of tetraalkylammonium ions with protein carboxylates OR Ionic >> Electrostatic interaction of tetraalkylammonium ions with protein carboxylates >> Tetraalkylammonium ions OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-carbonyl compounds with polarized double bonds OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Vinyl sulfonyl compounds OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Activated electrophilic ethenylarenes OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone (di)imines OR Michael addition >> Quinone type compounds >> Quinones OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Schiff base formation OR Schiff base formation >> Nucleophilic cycloaddition to diketones OR Schiff base formation >> Nucleophilic cycloaddition to diketones >> Diketones OR SN1 OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds OR SN2 >> Nucleophilic substitution at Nitrogen atom OR SN2 >> Nucleophilic substitution at Nitrogen atom >> N-oxicarbonyl amides OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Activated alkyl esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Phosphates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Sulfonates OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes OR SN2 Ionic OR SN2 Ionic >> Nucleophilic substitution at sulfur atom in disulfides OR SN2 Ionic >> Nucleophilic substitution at sulfur atom in disulfides >> Arenesulfinic acids OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.52

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.92

Conclusions:

In a subacute repeated dose toxicity study of Eicosanoic acid to female Sprague-Dawley rat at a dose level of 1500 mg/kg bw/day (nominal) by gavage.No effects observed on mortality,bodyweight ,food consumption ,reproduction and on morphology. Thus the no observed effect level (NOEL) for repeated dose toxicity study was considered to be 1500 mg/kg bw/day (nominal).

Executive summary:

WoE Summary (Repeated dose toxicity :oral)

The NOEL for target chemicalEicosanoic acid (CAS No.: 506-30-9) is estimated to be 1500 mg/kg bw/day (nominal) for Sprague-Dawley rat for 14 days using the toolbox version 3.2. The data is estimated to be based on the data summarized below

CAS no.	End point	Value	Species	Doses	Duration	Effects	Remarks
112-85-6	NOEL	1000 mg/kg /day	Rat(Sprague-Dawley)	100- 1000 mg/kg/day	NA	Mortality,body weight decrease,food consumption decrease,abnormal breathing ,absolute organ weight increase etc.	Oral-gavage
112-05-0	NOEL	1500 mg/kgbw	Rat(Sprague-Dawley)	1500 mg/kgbw	14 days	No effects observed on the following parameter :Growth,feeding behavior,mortality,reproduction,morphology etc.	Oral -gavage
112-05-0	NOEL	1500 mg/kgbw	Rat(Sprague-Dawley)	1500 mg/kgbw	9 days	No effects observed on the following parameter :Development,morphology,reproduction	Oral -gavage

Based on the studies summarized in the above table it can be observed that the no observed effect value(NOEL) varies from1000 mg/kg /day to 1500 mg/kg bw.The no effect observed for the following parameters on the above doses are-

*No effects observed on the following parameter :Growth,feeding beh avi or,morta lity,reproduction ,morphology etc.

*No effects observed on mortality,body weight decrease,food consumption decrease,abnormal breathing ,absolute organ weight increase etc.

*No effects observed on the following parameter :Development,morphology,reproduction

Thus based on the above results it can be concluded thatthe estimated value for the target substance (506-30-9) is more closed to the NOEL value of the read across substance (CAS :112-05-0) which is reported as 1500 mg/kgbw and thus the no observed effect level (NOEL) for repeated dose toxicity study for target substance was considered to be1500 mg/kg bw/day (nominal)when administered orally in a subacute study of 14 days.At this dose concentration no effects observed on mortality,bodyweight ,food consumption ,reproduction and morphology.

Endpoint conclusion:

no adverse effect observed

1 500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Reference

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

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

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

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes

ORGAN WEIGHT : Yes

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

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.

Critical effects observed:

not specified

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

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.

Endpoint conclusion:

no adverse effect observed

238.2

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Endpoint conclusion:

no study available

Reference

Endpoint:: repeated dose toxicity: dermal
Data waiving:: exposure considerations
Justification for data waiving:: other:
Critical effects observed:: not specified

Endpoint conclusion:

no adverse effect observed

Endpoint conclusion:

no study available

Repeated dose toxicity (Oral)

WoE Summary of 506-30-9 for repeated dose toxicity

Based on the various studies available with Klimish rating 2 and 4 for the target as well as the read across substances for CAS: 506-30-9 based on the category approach of organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox.

The results for target as well as analogues are summarized as follows

Sr. No	End point	Value	Species	Route	Effects	Remarks
1	NOEL	1500 mg/kg bw/day (nominal)	Rat	Oral (gavage)	No effects observed on mortality,bodyweight ,food consumption ,reproduction and on morphology.	Predicted data for CAS: 506-30-9
2	NOAEL	2090 mg/kg bw/day (nominal)	Rat	Oral (gavage)	No effects observed on mortality and body weight.	Predicted data for CAS: 506-30-9
3	NOAEL LOAEL	1000 mg/kg/day >1000 mg/kg/day	Rat	Oral (gavage)	There were no treatment-related adverse effects though some slight changes in blood biochemistry and histopathology in testes. Some slight changes in blood biochemistry and histopathology in testes was observed.	Data from study report for RA CAS: 112-85-6
4	NOAEL	25200 mg/kg bw	Rat	Oral (feed)	Disappearance of the lipogranuloma, no signs of permanent scarring or necrosis in the adipose tissue.	Data from publication for RA CAS: 57-10-3
5	LOAEL	3000 mg/kg	Rat	Oral (feed)	Causing anorexia, weight loss, and increased mortality.Whereas no histopathological findings were observed during the study.	Data from publication for RA CAS: 57-11-4

Based on the studies summarized in the above table with oral routes it can be observed that the no observed effect value varies (NOEL and NOAEL) from 1000 mg/kg/day to 25200 mg/kg bw and low observed effect value (LOAEL) varies from >1000 mg/kg /day to 3000 mg/kg based on the predicted data as well as data from publication for target and read across substance. The effect observed on the above doses are-

· Some slight changes in blood biochemistry and histopathology in testes was observed.

. Causing anorexia, weight loss, and increased mortality.Whereas no histopathological findings were observed during the study.

· No effects observed on mortality,bodyweight ,food consumption ,reproduction and on morphology.

· No treatment-related adverse effects though some slight changes in blood biochemistry and histopathology in testes.

· Disappearance of the lipogranuloma, no signs of permanent scarring or necrosis in the adipose tissue.

Thus based on the above results it can be concluded that substance CAS: 506-30-9 is expected to show the similar toxicological effect based on the effects observed on the other category members.Since the no effective dose value (NOAEL) is greater than 25200 mg/kg bw thus based on this value it can be concluded that substance CAS: 506-30-9 is considered to be not toxic to repeated dose via oral route at concentration at 25200 mg/kg bw or lower when administered orally.Also There are no known evidence of adverse effect to human of CAS: 506-30-9 and no mechanistic trigger indicate the toxicity of substance CAS: 506-30-9 via repeated dose toxicity via oral route.

Repeated dose toxicity: inhalation

WoE Summary

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.

Repeated dose toxicity: dermal

Repeated dermal toxicity is unlikely to occur since dermal absorption of Eicosanoic acid is very low based on the value 0.00010 mg/cm2/event. Also considering the use of the chemical as a cosmetic agents , used in the production of detergents, photographic materials, softener & dispersing agent, food packaging and lubricants and considering the volatility absorption by the dermal route is not considered to be significant. Thus, given the above considerations, it is assumed that Eicosanoic acid shall not exhibit repeated dose toxicity by the dermal route.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

In a subacute repeated dose toxicity study of Eicosanoic acid to female Sprague-Dawley rat at a dose level of 1500 mg/kg bw/day (nominal) by gavage.No effects observed on mortality,bodyweight ,food consumption ,reproduction and on morphology. Thus the no observed effect level (NOEL) for repeated dose toxicity study was considered to be 1500 mg/kg bw/day (nominal).

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

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.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

Repeated dermal toxicity is unlikely to occur since dermal absorption of Eicosanoic acid is very low based on the value 0.00010 mg/cm2/event. Also considering the use of the chemical as a cosmetic agents , used in the production of detergents, photographic materials, softener & dispersing agent, food packaging and lubricants and considering the volatility absorption by the dermal route is not considered to be significant. Thus, given the above considerations, it is assumed that Eicosanoic acid shall not exhibit repeated dose toxicity by the dermal route.

The substance do not show repeated dose toxicity effect for oral,inhalation and dermal route and thus will not be considered for further classification.