4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction:

Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride is estimated to be 546.66 mg/Kg bw/day.

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.4 with log Kow as the primary descriptor.

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

Details on study schedule:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Parental animals: Observations and examinations:

not specified

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

not specified

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

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

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

not specified

Basis for effect level:

reproductive performance

other: no significant changes were noted at mentioned dose level

Critical effects observed:

not specified

Mortality / viability:

no mortality observed

Remarks on result:

other: not specified

Critical effects observed:

not specified

Reproductive effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" )  and ("c" and ( not "d") )  )  and ("e" and ( not "f") )  )  and ("g" and "h" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.35

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.23

Conclusions:

Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride is estimated to be 546.66 mg/Kg bw/day.

Executive summary:

Toxicity to reproduction was evaluated for 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride using SSS QSAR prediction database V3.4. The study assumed the use of rats in a subacute study. Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for 4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride is estimated to be 546.66 mg/Kg bw/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

546.66 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is of K2 reliability and is obtained from QSAR toolbox.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to reproduction:

Predicted data for the target chemical along with its structurally related substance were reviewed to determine the toxic nature of 4,4'-carbonimidoylbis(N,N-diethylaniline) monohydrochloride for reproductive toxicity. The summary is presented below as weight of evidence approach:

Toxicity to reproduction was evaluated for4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride using SSS QSAR prediction database V3.4. The study assumed the use of rats in a subacute study. Since no significant changes were noted relating to effects on reproductive toxicity in rats, the No Observed Adverse Effect Level (NOAEL) for4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochlorideis estimated to be 546.66 mg/Kg bw/day.

Three groups of five mated female rats were administered structurally related substance Acid Red 52 (CAS 3520 -42 -1) by gavage at doses of 100, 300 or 1000 mg/kg bw/day from day 6 through day 17 post coitum (cited inTHE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP) /0803/ 23 April 2004). An additional group of five mated rats was administered the vehicle (bi-distilled water containing 1% carboxymethyl cellulose sodium salt) and served as a control group. On day 21 post coitum, the animals were killed and examined macroscopically. Foetuses were removed by Caesarean section. No death occurred during the course of the study. Violet discoloured faeces, urine and bedding material were noted from day 7 post coitum till day 19 post coitum in all treatment groups. The relevant maternal reproductive data (mean number of implantations and live foetuses) were similar in all groups. No external abnormalities were noted in any of the foetuses. The sex ratios were similar in all groups. Based on the results described above, 1000 mg/kg bw/day of sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate (Acid Red 52) is considered to be the No-Observable-Adverse-Effect-Level (NOAEL) for the maternal/ reproductive toxicity.

Based on the data summarized and by applying weight of evidence approach, it can be concluded that 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride is not likely to be toxic for reproductive toxicity. Thus, the chemical is not classified as a toxicant as per the criteria mentioned in CLP regulation.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data summarized and by applying weight of evidence approach, it can be concluded that 4,4'-carbonimidoylbis(N,N-diethylaniline) hydrochloride is not likely to be toxic for reproductive toxicity. Thus, the chemical is not classified as a toxicant as per the criteria mentioned in CLP regulation.