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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: combined repeated dose and reproduction / developmental screening;fertility
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
other: Predicted data
Title:
293 mg/kg bw/day (actual dose received); Estimation for NOAEL reproductive toxicity for Cas no:130-26-7
Author:
Sustainabilty Support Services Europe (AB)
Year:
2014
Bibliographic source:
SSS QSAR Prediction Team

Materials and methods

Test guideline
Guideline:
other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test);OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (study number
Principles of method if other than guideline:
Prediction using category approach; QSAR Toolbox 3.1; Read Across; 5 nearest analogues; Log Kow as descriptor
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Clioquinol
EC Number:
204-984-4
EC Name:
Clioquinol
Cas Number:
130-26-7
Molecular formula:
C9H5ClINO
IUPAC Name:
5-chloro-7-iodoquinolin-8-ol
Details on test material:
SMILES:c1(I)c(O)c2c(c(Cl)c1)cccn2

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
14 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 30, 100, 300, 1000 mg/kg
Basis:

No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
293 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects were observed
Remarks on result:
other: not specified

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified

Results: F2 generation

Effect levels (F2)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOEL,"NOEL reproductive/developmental toxicity","NOAEL reproduction","NOEL overall","NOAEL developmental","NOAEL for parental toxicity","NOAEL for reproductive toxicity",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" or "g" )  and ("h" and ( not "i") )  )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Phenol AND Pyridine AND Quinoline/ Isoquinoline by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl halide AND Overlapping groups AND Phenol AND Quinoline/ Isoquinoline by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Hydroxy, aromatic attach [-OH] AND Iodide, aromatic attach [-I] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Aryl chloride AND Aryl halide AND Aryl iodide AND Halogen derivative AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At AND Group 17 - Halogens I by Chemical elements

Domain logical expression index: "g"

Similarity boundary:Target: c1(I)c(O)c2c(c(Cl)c1)cccn2
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkylphenols OR Parabens OR Phenylphenols by rtER Expert System ver.1 - USEPA

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.39

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.48

Applicant's summary and conclusion

Conclusions:
The NOAEL (No observed adversed effect level) of clioquinol was observed at a dose level of 293 mg/kg/day.
Executive summary:

WoE Summary for Cas: 130-26-7

 

The NOAEL value of clioquinolisestimated to be 293 mg/kg bw/day (actual dose received) for duration of 14 days on rat using the toolbox version 3.2.

The data is estimated to be based on the data summarized below

Sr no.

CAS no

End point

Value

Species

Doses

Duration

Effects

Remarks

1

118-79-6

NOAEL reproduction

1000mg/kg bw/day (actual dose received)

Rat

0, 30, 100, 300, 1000 mg/kg

14 days

No effect was seen on hematological parameters. High tissue weights for livers and kidneys

 

118-79-6

NOAEL reproduction

300 mg/kg bw/day (actual dose received)

Rat

0, 30, 100, 300, 1000 mg/kg

14 days

No adverse effects were observed

 

2

128-39-2

NOAEL

150 mg/kg bw/day (actual dose received)

Rat

30, 150, 750 mg/kg bw/day

14 days

No teratogenic effect was observed at external examination and necropsy

 

3

80-09-1

NOAEL for reproductive toxicity

60 mg/kg bw/day (actual dose received

Rat

0, 10, 60 and 300 mg/kg bw/day

males 45 days, females from 14 days

No effects were observed on estrous cycles, fertility index, number of implantations, implantation index, number of live births and number of live offspring

 

4

 

NOEL reproductive/developmental toxicity

1000 mg/kg bw/day (actual dose received)

Rat

0, 40, 200, 1000 mg/kg bw./day

Male:42 days &female:28 days

No effects on mortality, food consumption, organ weights, number of mated pairs, number of copulated pairs, copulation index, number of pregnant animals

 

 

The above table consist of various reproductive toxicity studies available for the read across substances for CAS: 130-26-7.Based on the above results it can be observed that NOAEL or NOEL values are in the range of 60 - 1000 mg/kg bw./day and .The no effects observed on the above doses are listed as follows.

·        Effect was seen on hematological parameters. weights of livers and kidneys

·         teratogenic effect was observed at external examination and necropsy

·        estrous cycles, fertility index, and number of implantations, implantation index, number of live births and number of live offspring.

·        mortality, food consumption, organ weights, number of mated pairs, number of copulated pairs, copulation index, number of pregnant animals

Thus based on above discussion it can be concluded that estimated value 293 mg/kg bw/day for the substance (CAS: 130-26-7) is more closed to 300 mg/kg bw/day in sub-acute duration for rat