Registration Dossier

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

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:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Males, 42 days; Females, from 14 days prior to mating to day 3 of lactation.

Frequency of treatment:

Daily

Control animals:

not specified

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

370 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Remarks on result:

not measured/tested

Reproductive effects observed:

not specified

Treatment related:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL,"NOEL (fertility)"
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 ( not "h") ) ) and "i" ) and ("j" and "k" ) )

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 Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "h"

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: "i"

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: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0443

Domain logical expression index: "k"

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

Conclusions:

In a two generation reproductive study of Eicosanoic acid to male/female Crj: CD(SD) rat by gavage,no compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs at a dose level of 370 mg/kg bw/day (nominal). Thus the (No observed adverse effect level) NOAEL for reproductive toxicity study was considered to be 370 mg/kg bw/day (nominal).

Executive summary:

WoE Summary (Toxicity to reproduction)

The NOAEL for target chemical Eicosanoic acid (CAS No.: 506-30-9) is estimated to be 370 mg/kg bw/day (nominal) for Crj: CD(SD) rat 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
112-85-6	NOAEL	1000 mg/kg/day	Crj: CD(SD) Rats	0(vehicle), 100, 300, 1,000 mg/kg/day.	Males, 42 days; Females, from 14 days prior to mating to day 3 of lactation.(Two-generation study)	No compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs.
110-16-7	LOEL	20 mg/kg bw/day	Charles River CD rats	0, 20, 55, and 150 mg/kg	- P/F0: from study initiation to the end of the generation - F1: at 22 days of age and continued throughout the generation (Premating (Premating exposure period: F0 and F1, a minimum of 80 days) and throughout mating, gestation and lactation) (Two-generation study)	Reduced fertility in males and females, however, neither a dose-related reduction nor a pattern within a generation suggested a treatment-related effect.
110-16-7	NOEL	55 mg/kg/day	Charles River CD rats	0, 20, 55, and 150 mg/kg	- P/F0: from study initiation to the end of the generation - F1: at 22 days of age and continued throughout the generation (Premating (Premating exposure period: F0 and F1, a minimum of 80 days) and throughout mating, gestation and lactation) (Two-generation study)	No effects observed on clinical signs,mortality,body weight and food consumption and gross pathology.

Based on the studies summarized in the above table it can be observed that the no observed effect value (NOEL and NOAEL) varies from 55 mg/kg/day to 1000 mg/kg/day and low observed effect value (LOEL) was found to be 20 mg/kg bw/day.The effect observed on the above doses are-

* Reduced fertility in males and females, however, neither a dose-related reduction nor a pattern within a generation suggested a treatment-related effect.

*No compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs.

*No effects observed on clinical signs,mortality, body weight and food consumption and gross pathology.

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 NOAEL value of the read across substance (CAS :112-85-6) which is reported as 1000 mg/kg/day whereas other LOEL and NOEL values are extrapolating from the target value and thus the no observed adverse effect level (NOAEL) for reproductive toxicity study for target substance was considered to be 370 mg/kg bw/day(nominal) when administered by gavage in a two generation study period.At this dose concentration no compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

370 mg/kg bw/day

Study duration:

subchronic

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

Endpoint conclusion:

no study available

Toxicity to reproduction

WoE Summary of 506-30-9 for toxicity to reproduction

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. This data is combined with the prediction done using the QSAR toolbox for the target chemical based on similar category approach, the results are summarized as follows

Sr. No

End point

Value

Species

Route

Effects

Remarks

1

NOAEL

370 mg/kg bw/day (nominal)

Rat

Oral

No compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs.

Predicted data for target chemical (506-30-9)

2

NOAEL

1000 mg/kg bw/day

Rat

Oral

No abnormalities were found in all reproductive parameters (fertility index, number of implantations and implantation index) in each dose group as well as no effects on mortality,body weight food consumption and organ weights.

Experimental data from study report for RA CAS : 112-85-6

Based on the studies summarized in the above table it can be observed that the endpoint no effect value (NOAEL) varies from 370 mg/kg bw/day (nominal) to 1000 mg/kg bw/day based on the data from prediction as well as publication for target & read across substance. The effect observed on the above doses are-

· No compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs.

· No abnormalities were found in all reproductive parameters (fertility index, number of implantations and implantation index) in each dose group as well as no effects on mortality,body weight food consumption and organ weights.

Thus based on the above results it can be concluded that the substance CAS: 506-30-9 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since no effective dose value (NOAEL) is higher than 1000 mg/kg bw/day thus based on this value it can be concluded that substance CAS: 506-30-9 is considered to be not toxic to reproduction at concentration at 1000 mg/kg bw/day or lower. Also there are no known evidence of adverse effect on reproduction to human of CAS: 506-30-9.

Short description of key information:

From the various data available and adopting the weight of evidence approach, it has been concluded that Eicosanoic acid is not likely to have reprotoxic effects.

Justification for selection of Effect on fertility via oral route:

In a two generation reproductive study of Eicosanoic acid to male/female Crj: CD(SD) rat by gavage,no compound related changes were observed in length of gestation period and any parameters during gestation, delivery and lactation. The compound showed no adverse effects on copulation or fertility., body weights,food consumption and clinical signs at a dose level of 370 mg/kg bw/day (nominal). Thus the (No observed adverse effect level) NOAEL for reproductive toxicity study was considered to be 370 mg/kg bw/day (nominal).

From the various data available and adopting the weight of evidence approach, it has been concluded that Eicosanoic acid is not likely to have teratogenic effects.

Reference

Endpoint:

developmental toxicity

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:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Wistar

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

day 6 - 15 of gestation

Frequency of treatment:

daily

Duration of test:

upto gestation day 20

Control animals:

not specified

Fetal examinations:

Fetal weight was examined.

Details on maternal toxic effects:

Maternal toxic effects:no data

Dose descriptor:

LOEL

Effect level:

720 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Fetal weight decreased.

Dose descriptor:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

other: not specified

Description (incidence and severity):

not specified

Developmental effects observed:

not specified

Treatment related:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL,LOEL,NOEL
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 >= 2.95

Domain logical expression index: "aa"

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

Conclusions:

In a developmental toxicity study of Eicosanoic acid to wistar rats by gavage at a dose level of 720 mg/kg bw/day (nominal),resulted in a decreased fetal weight. Thus the (lowest observed effect level) LOEL for developmental toxicity study was considered to be 720 mg/kg bw/day (nominal), it is regarded that at concentrations lower than 720 mg/kg bw/day (nominal) there will be no developmental toxic effects when administered orally.

Executive summary:

WoE Summary (Developmental toxicity)

The NOAEL for target chemical Eicosanoic acid (CAS No.: 506-30-9) is estimated to be 720 mg/kg bw/day(nominal) for Wistar rat 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
112-85-6	NOAEL	1000 mg/kg/day	Crj: CD(SD) Rat	0(vehicle), 100, 300, 1,000 mg/kg/day	Males, 42 days; Females, from 14 days prior to mating to day 3 of lactation.	No morphological abnormalities in external and visceral observation in pups were observed in any of the treated groups.
149-57-5	LOEL	600 mg/kg/day	Wistar Rats	100 , 300 , 600 mg/kg/day	20 days	Fetal weight decreased.
149-57-5	NOEL	>250 mg/kg bw/day	New Zealand White Rabbit	0, 25, 125 or 250 mg/kg bodyweight/day	Up to gestation day 29	No effects observed.

Based on the studies summarized in the above table it can be observed that the low observed effect value (LOEL) was found to be 600 mg/kg/day and the no observed effect value (NOAEL) varies from >250 mg/kg bw/day to 1000 mg/kg/day.The effect observed on the above doses are-

* Fetal weight decreased.

* No morphological abnormalities in external and visceral observation in pups were observed in any of the treated groups.

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 : 149-57-5) which is reported as 600 mg/kg/day because NOEL values are extrapolating from the target value and thus the low observed effect level (LOEL) for reproductive toxicity study for target substance in a 20 days study period was considered to be 720 mg/kg bw/day(nominal),resulted in decreased fetal weight.

Endpoint conclusion:

no adverse effect observed

720 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.

Endpoint conclusion:

no study available

Endpoint conclusion:

no study available

WoE Summary of 506-30-9 for developmental 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. This data is combined with the prediction done using the QSAR toolbox for the target chemical based on similar category approach, the results are summarized as follows

Sr. No	End point	Value	Species	Route	Effects	Remarks
1	LOEL (Developmental toxicity)	720 mg/kg bw/day (nominal)	Wistar, rat	Oral(gavage)	Fetal weight decreased	Predicted data for target chemical (506-30-9 )
2	End point not reported (Teratogenicity study)	-	Human		No effects observed.	Predicted data for target chemical (506-30-9 )
3	NOAEL (fetotoxicity)	1000 mg/kg bw/day	Crj: CD(SD),Rat	Oral(gavage)	No abnormalities were found in all indexes (No. of pups born, No. of pups alive, pups weight, sex ratio,viability etc.) obtained from pups in each dose group.	Data from study report for RA CAS : 112-85-6

Based on the studies summarized in the above table with various routes it can be observed that the low observed effect level (LOEL) was found to be 720 mg/kg bw/day (nominal) and the no observed effect level (NOAEL) to be 1000 mg/kg bw/day based on the data from prediction as well as publication for target &read across substance. The effect observed on the above doses are-

· Fetal weight decreased.

· No abnormalities were found in all indexes (No. of pups born, No. of pups alive, pups weight, sex ratio,viability etc.) obtained from pups in each dose group.

Thus based on the above results it can be concluded that substance CAS: 506-30-9 is expected to show the similar toxicological effects based on the effects observed on the other category members. Since no effective dose value (NOAEL) is higher than 1000 mg/kg bw/day thus based on this value it can be concluded that substance CAS: 506-30-9 is considered to be not toxic to teratogenic effects at concentration at 1000 mg/kg bw/day or lower.Also there are no known evidence of adverse effect on reproduction to human of CAS: 506-30-9.

Justification for selection of Effect on developmental toxicity: via oral route:

In a developmental toxicity study of Eicosanoic acid to wistar rats by gavage at a dose level of 720 mg/kg bw/day (nominal),resulted in a decreased fetal weight. Thus the (lowest observed effect level) LOEL for developmental toxicity study was considered to be 720 mg/kg bw/day (nominal), it is regarded that at concentrations lower than 720 mg/kg bw/day (nominal) there will be no developmental toxic effects when administered orally.

From the NOAEL and LOAEL values obtained for Eicosanoic acid for toxicity to reproduction as well as developmental toxicity, it is considered that the chemical does not qualify for classification as a reproductive or developmental toxicant.